51 results on '"Mila Etropolski"'
Search Results
2. A Pooled Analysis Evaluating the Efficacy and Tolerability of Tapentadol Extended Release for Chronic, Painful Diabetic Peripheral Neuropathy
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C. Rauschkolb, Mila Etropolski, Sherwyn Schwartz, Juergen Haeussler, Bernd Lange, Douglas Y. Shapiro, Aaron I. Vinik, Kimberly Cooper, and Ilse Van Hove
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Male ,Analgesic ,Receptors, Opioid, mu ,Placebo ,Phenols ,Humans ,Medicine ,Diabetic Nephropathies ,Pharmacology (medical) ,Original Research Article ,Aged ,Analgesics ,business.industry ,Drug Tolerance ,General Medicine ,Middle Aged ,medicine.disease ,Tapentadol ,Confidence interval ,Peripheral neuropathy ,Opioid ,Tolerability ,Delayed-Action Preparations ,Anesthesia ,Chronic Disease ,Neuropathic pain ,Female ,business ,medicine.drug - Abstract
Background and Objective Data from two similarly designed studies of tapentadol extended release (ER) for managing neuropathic pain associated with diabetic peripheral neuropathy (DPN; NCT00455520, NCT01041859) in adults were pooled for this analysis, allowing a detailed evaluation of efficacy in patient subgroups and secondary endpoints. Methods In each study, patients were titrated to their optimal dose of open-label tapentadol ER [100–250 mg twice daily (bid)] over 3 weeks. Patients with ≥1-point improvement in average pain intensity [11-point numerical rating scale (NRS)] were randomized (1:1) to receive placebo or tapentadol ER during a 12-week, double-blind maintenance period. Results Mean (standard deviation [SD]) changes in pain intensity from baseline to week 12 of maintenance in the placebo (n = 343) and tapentadol ER (n = 360) groups, respectively, were 1.28 (2.41) and 0.08 (1.87) [least squares mean difference (LSMD): −1.14 (95 % confidence interval [CI]: −1.435, −0.838); P
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- 2014
3. A Randomized Withdrawal, Placebo-Controlled Study Evaluating the Efficacy and Tolerability of Tapentadol Extended Release in Patients With Chronic Painful Diabetic Peripheral Neuropathy
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C. Rauschkolb, Aaron I. Vinik, Bernd Lange, Deborah Pennett, Douglas Y. Shapiro, Mila Etropolski, and Keith Karcher
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Adult ,Male ,Adolescent ,Vomiting ,Endocrinology, Diabetes and Metabolism ,Placebo-controlled study ,Placebo ,law.invention ,Placebos ,Young Adult ,Diabetic Neuropathies ,Double-Blind Method ,Phenols ,Randomized controlled trial ,law ,Internal Medicine ,medicine ,Clinical endpoint ,Humans ,Aged ,Aged, 80 and over ,Advanced and Specialized Nursing ,business.industry ,Chronic pain ,Nausea ,Middle Aged ,medicine.disease ,Tapentadol ,Treatment Outcome ,Peripheral neuropathy ,Withholding Treatment ,Tolerability ,Delayed-Action Preparations ,Anesthesia ,Female ,Chronic Pain ,business ,medicine.drug - Abstract
OBJECTIVE This study evaluated the efficacy and tolerability of tapentadol extended release (ER) for the management of chronic pain associated with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Adults with moderate to severe DPN pain were titrated to tapentadol ER 100–250 mg bid during a 3-week open-label period; patients with ≥1-point reduction in pain intensity (11-point numerical rating scale) at end of titration were randomized to receive placebo or tapentadol ER (optimal dose from titration) for 12 weeks (double-blind, fixed-dose maintenance phase). The primary end point was mean change in average pain intensity from the start to week 12 (last observation carried forward [LOCF]) of the double-blind maintenance phase. RESULTS A total of 358 patients completed the titration period; 318 patients (placebo, n = 152; tapentadol ER, n = 166) were randomized and received one or more doses of double-blind study medication. Mean (SD) pain intensity (observed case) was 7.33 (1.30) at the start and 4.16 (2.12) at week 3 of the open-label titration period (mean [SD] change, –3.22 [1.97]). The mean (SD) change in pain intensity (LOCF) from start of double-blind treatment to week 12 was as follows: placebo, 1.30 (2.43); tapentadol ER, 0.28 (2.04; least squares mean difference, –0.95 [95% CI –1.42 to –0.49]; P < 0.001). Treatment-emergent adverse events (≥10%) in the tapentadol ER group during the double-blind maintenance phase were nausea (21.1%) and vomiting (12.7%). CONCLUSIONS Tapentadol ER (100–250 mg bid) was effective and well tolerated for the management of moderate to severe chronic pain associated with DPN.
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- 2014
4. Evaluation of Blood Pressure and Heart Rate in Patients with Hypertension Who Received Tapentadol Extended Release for Chronic Pain: A Post Hoc, Pooled Data Analysis
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Mila Etropolski, David M. Biondi, Jim Xiang, and Bruce L. Moskovitz
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Male ,Analgesic ,Statistics as Topic ,Receptors, Opioid, mu ,Blood Pressure ,law.invention ,Randomized controlled trial ,Double-Blind Method ,Phenols ,law ,Heart Rate ,Heart rate ,medicine ,Humans ,Pharmacology (medical) ,Original Research Article ,Aged ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,Osteoarthritis, Knee ,Tapentadol ,medicine.disease ,Clinical trial ,Blood pressure ,Opioid ,Anesthesia ,Delayed-Action Preparations ,Hypertension ,Female ,Chronic Pain ,business ,medicine.drug - Abstract
Background and Objectives Hypertension is one of the most common co-existing conditions in patients with chronic pain, and the potential effects of an analgesic on heart rate and blood pressure are of particular concern for patients with hypertension. The purpose of this analysis was to evaluate changes in blood pressure and heart rate with tapentadol extended release (ER) treatment in patients with hypertension. Methods We performed a post hoc analysis of data pooled from three randomized, placebo- and active-controlled, phase III studies of tapentadol ER for managing chronic osteoarthritis knee (NCT00421928, NCT00486811) or low back (NCT00449176) pain (15-week, double-blind treatment period). Data were independently analyzed for patients with a listed medical history of hypertension at baseline and patients with at least one listed concomitant antihypertensive medication at baseline. Heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured at each visit. Results In patients with a listed medical history of hypertension (n = 1,464), least-squares mean (LSM [standard error (SE)]) changes from baseline to endpoint with placebo, tapentadol ER, and oxycodone HCl controlled release (CR), respectively, were −0.7 (0.44), 0.2 (0.43), and −0.9 (0.45) beats per minute (bpm) for heart rate; −2.4 (0.64), −2.7 (0.64), and −3.7 (0.67) mmHg for SBP; and −1.0 (0.39), −1.3 (0.39), and −2.3 (0.41) mmHg for DBP; in patients with at least one listed concomitant antihypertensive medication (n = 1,376), the LSM (SE) changes from baseline to endpoint were −0.6 (0.45), 0.1 (0.44), and −0.7 (0.47) bpm for heart rate; −1.8 (0.66), −3.3 (0.65), and −3.7 (0.69) mmHg for SBP; and −0.7 (0.40), −1.4 (0.40), and −2.3 (0.42) mmHg for DBP. Conclusion No clinically meaningful mean changes in heart rate or blood pressure were observed for the evaluated cohorts of patients with hypertension who were treated with tapentadol ER (100–250 mg twice daily).
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- 2014
5. Quantifying the Exposure of Tapentadol Extended Release in Japanese Patients with Cancer Pain and Bridging Tapentadol Pharmacokinetics Across Populations Using a Modeling Approach
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Partha Nandy, Peter Zannikos, Liping Zhang, Mila Etropolski, Xiaoyu Yan, and Sayori Nobe
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Population ,030226 pharmacology & pharmacy ,Models, Biological ,White People ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pharmacokinetics ,Phenols ,030202 anesthesiology ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Young adult ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Healthy subjects ,General Medicine ,Cancer Pain ,Middle Aged ,Tapentadol ,Anesthesia ,Meta-analysis ,Delayed-Action Preparations ,Female ,Extended release ,business ,Cancer pain ,medicine.drug - Abstract
Tapentadol extended release (ER) is approved for the management of chronic and acute pain in adults. There has been no report of tapentadol ER pharmacokinetics in subjects with cancer pain. This analysis investigated tapentadol ER pharmacokinetics in Japanese patients with cancer pain and bridged it with the pharmacokinetics in Japanese healthy subjects and Caucasian patients with cancer pain. Nonlinear mixed-effect pharmacokinetic modeling was conducted based on pooled tapentadol ER concentration data collected in five Phase 1 studies from 138 Japanese and Korean healthy subjects and in two Phase 3 studies from 215 Japanese and Korean subjects with cancer pain. Expected tapentadol exposure in subjects with different characteristics was assessed via simulation. Tapentadol ER exposures in Caucasian populations were compared with those in corresponding Japanese populations. Tapentadol ER pharmacokinetics in Japanese cancer-pain patients were adequately described by a time-invariant, one-compartment disposition model with two input functions and first-order elimination. Weight, age, and albumin were identified as statistically significant covariates, but do not warrant dose adjustment. Comparable pharmacokinetics were shown between Japanese healthy and Caucasian healthy subjects, and between Japanese cancer-pain patients and Caucasian cancer-pain patients. The apparent differences in the estimated individual pharmacokinetic parameters in Japanese healthy subjects and Japanese cancer-pain patients taking tapentadol ER were explained by covariates incorporated in a unified pharmacokinetic model. Population modeling was essential in this cross-population bridging analysis.
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- 2016
6. Methodological Issues in Conducting Pilot Trials in Chronic Pain as Randomized, Double-blind, Placebo-controlled Studies
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Yushin Tominaga, N Uchida, Taka Matsumura, H Koga, U Richarz, Mila Etropolski, Mikio Wanibe, A Okamoto, and Keiichiro Hirose
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Adult ,Pilot Projects ,Placebo ,law.invention ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,Phenols ,law ,Drug Discovery ,medicine ,Humans ,030212 general & internal medicine ,Pain Measurement ,Randomized Controlled Trials as Topic ,Analgesics ,business.industry ,Chronic pain ,General Medicine ,Tapentadol ,medicine.disease ,Low back pain ,Clinical trial ,Knee pain ,Peripheral neuropathy ,Anesthesia ,Delayed-Action Preparations ,medicine.symptom ,Chronic Pain ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background: The efficacy of tapentadol extended release (ER) for managing chronic pain has been demonstrated in large-scale, randomized, controlled, phase 3 studies (N=318–1,030) in patients with chronic osteoarthritis (OA) pain, low back pain (LBP), and pain related to diabetic peripheral neuropathy (DPN), which led to registration in many regions, including the United States and Europe. 2 pilot 12-week, randomized, double-blind, placebo-controlled phase 2 studies of tapentadol ER for chronic pain (OA knee pain or LBP, n=91; DPN or peripheral herpetic neuralgia [PHN] pain; n=91) were conducted in Japan. These small exploratory studies were substantially underpowered compared with the registration trials. Methods: Patients in both studies were randomized (2:1) to tapentadol ER (25–250 mg) or placebo for 12 weeks (≤6-week titration plus maintenance periods). Results: For the primary efficacy endpoint (change in pain intensity from baseline to last week of treatment; last observation carried forward), both studies failed to differentiate between tapentadol ER and placebo; least-squares mean differences (95% confidence intervals) for tapentadol ER vs. placebo were −0.1 (−1.04, 0.80) in the OA/LBP study and −0.1 (−1.10, 0.99) in the DPN/PHN study. More than 80% of patients took concomitant analgesics during these studies. Tapentadol was well tolerated. Conclusions: Both studies were associated with methodological issues, including populations with different disease entities, small sample sizes, use of concomitant analgesics, and possible placebo effect that may have led to the failure to differentiate between tapentadol ER and placebo.
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- 2016
7. Tolerability and efficacy of tapentadol extended release in elderly patients ≥ 75 years of age with chronic osteoarthritis knee or low back pain
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David M. Biondi, Jim Xiang, Bruce L. Moskovitz, and Mila Etropolski
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Male ,Analgesic ,Receptors, Opioid, mu ,Placebo ,Double-Blind Method ,Phenols ,Medicine ,Humans ,Pain Management ,Pharmacology (medical) ,Aged ,Retrospective Studies ,business.industry ,Chronic pain ,General Medicine ,Drug Tolerance ,Osteoarthritis, Knee ,Tapentadol ,medicine.disease ,Low back pain ,Anesthesiology and Pain Medicine ,Treatment Outcome ,Tolerability ,Opioid ,Anesthesia ,Delayed-Action Preparations ,Chronic Disease ,Female ,medicine.symptom ,business ,Oxycodone ,Low Back Pain ,medicine.drug ,Follow-Up Studies - Abstract
Objective: Management of chronic pain in elderly adult patients is often complicated by analgesic medication–related side effects. This post hoc analysis of pooled data evaluated the tolerability and analgesic efficacy of tapentadol extended release (ER) compared with oxycodone controlled release (CR) in elderly adult patients ( ≥ 75 years of age) with moderate to severe, chronic osteoarthritis knee or low back pain. Methods: Data were pooled from three similarly designed, randomized, double-blind, placebo- and active-controlled, phase 3 studies of tapentadol ER for moderate to severe, chronic osteoarthritis knee (NCT00421928, NCT00486811) or low back (NCT00449176) pain, and data for patients ≥ 75 years of age were evaluated. Each study consisted of a 3-week titration and 12-week maintenance period. Patients received placebo, tapentadol ER (100-250 mg bid), or oxycodone HCl CR (20-50 mg bid). Tolerability was evaluated using adverse event reporting. Efficacy was evaluated using pain intensity ratings (11-point numerical rating scale). Results: For patients ≥ 75 years of age (n = 210), incidences of gastrointestinal treatment-emergent adverse events (TEAEs) overall and TEAEs of vomiting and the composite of nausea and/or vomiting were significantly lower in the tapentadol ER group compared with the oxycodone CR group (all p ≤ 0.0206). Tapentadol ER treatment was associated with significant reductions in pain intensity from baseline to week 15 compared with placebo (p = 0.0075); differences between the oxycodone CR and placebo groups failed to reach statistical significance (p = 0.1195), likely related to a higher treatment discontinuation rate in the oxycodone CR group. No significant differences were observed between the tapentadol ER and oxycodone CR groups in the change in pain intensity from baseline to week 15 (p = 0.2135). Conclusions: In elderly adult patients ≥ 75 years of age with moderate to severe, chronic osteoarthritis knee or low back pain, tapentadol ER (100-250 mg bid) provided significant pain relief compared with placebo and had a better overall gastrointestinal tolerability profile than oxycodone CR.
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- 2015
8. Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial
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Mila Etropolski, Akiko Okamoto, D.Y. Shapiro, Sherwyn Schwartz, Robert Lange, Christine Rauschkolb, and Juergen Haeussler
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Adult ,Male ,Treatment outcome ,Placebo-controlled study ,Pain ,law.invention ,Placebos ,Diabetic Neuropathies ,Double-Blind Method ,Phenols ,Randomized controlled trial ,law ,medicine ,Humans ,In patient ,Aged ,Pain Measurement ,Aged, 80 and over ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,medicine.disease ,Tapentadol ,Analgesics, Opioid ,Clinical trial ,Treatment Outcome ,Peripheral neuropathy ,Withholding Treatment ,Delayed-Action Preparations ,Anesthesia ,Female ,business ,Algorithms ,medicine.drug - Abstract
Painful diabetic peripheral neuropathy (DPN) may not be adequately managed with available therapeutic options. This phase III, randomized-withdrawal, placebo-controlled trial evaluated the safety and efficacy of tapentadol extended release (ER) for relieving painful DPN.Patients (n = 588) with at least a 3-month history of opioid and/or non-opioid analgesic use for DPN, dissatisfaction with current treatment, and an average pain intensity score of at least 5 on an 11-point numerical rating scale (NRS; 0 = 'no pain,' 10 = 'pain as bad as you can imagine') were titrated to an optimal dose of tapentadol ER (100-250 mg bid) during a 3-week open-label phase. Subsequently, patients (n = 395) with at least a 1-point reduction in pain intensity were randomized 1:1 to receive placebo or the optimal fixed dose of tapentadol ER determined during the open-label phase for a 12-week double-blind phase.NCT00455520.The primary efficacy outcome was the change in average pain intensity from randomization, determined by twice-daily NRS measurements. Safety was assessed throughout the study.The least-squares mean difference between groups in the change in average pain intensity from the start of double-blind treatment to week 12 was -1.3 (95% confidence interval, -1.70 to -0.92; p 0.001, tapentadol ER vs. placebo). A total of 60.5% (356/588) of patients reported at least a 30% improvement in pain intensity from the start to the end of the open-label titration phase; of the patients who were randomized to tapentadol ER, 53.6% (105/196) reported at least a 30% improvement from pre-titration to week 12 of the double-blind phase. The most common treatment-emergent adverse events that occurred during double-blind treatment with tapentadol ER included nausea, anxiety, diarrhea, and dizziness. Potential limitations of this study are related to the enriched enrollment randomized-withdrawal trial design, which may result in a more homogeneous patient population during double-blind treatment and may present a risk of unblinding because of changes in side effects from the open-label to the double-blind phase.Compared with placebo, tapentadol ER 100-250 mg bid provided a statistically significant difference in the maintenance of a clinically important improvement in pain 1 , 2 and was well-tolerated by patients with painful DPN.
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- 2010
9. Long-term Safety and Tolerability of Tapentadol Extended Release for the Management of Chronic Low Back Pain or Osteoarthritis Pain
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T. Häufel, Brigitte Kuperwasser, Mila Etropolski, Christine Rauschkolb, A. Steup, Stefan Grond, James E. Wild, Jane S. Gilbert, Robert Lange, Bettyanne McCann, and Bernd Lange
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business.industry ,Analgesic ,Tapentadol ,Low back pain ,law.invention ,Discontinuation ,Anesthesiology and Pain Medicine ,Randomized controlled trial ,Opioid ,Tolerability ,law ,Anesthesia ,medicine ,medicine.symptom ,business ,Oxycodone ,medicine.drug - Abstract
Background: Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action: µ-opioid receptor agonism and norepinephrine reuptake inhibition. This randomized, open-label phase 3 study (ClinicalTrials.gov Identifier: NCT00361504) assessed the long-term safety and tolerability of tapentadol extended release (ER) in patients with chronic knee or hip osteoarthritis pain or low back pain. Methods: Patients were randomized 4:1 to receive controlled, adjustable, oral, twice-daily doses of tapentadol ER (100 to 250 mg) or oxycodone HCl controlled release (CR; 20 to 50 mg) for up to 1 year. Efficacy evaluations included assessments at each study visit of average pain intensity (11-point numerical rating scale) over the preceding 24 hours. Treatment-emergent adverse events (TEAEs) and discontinuations were monitored throughout the study. Results: A total of 1,117 patients received at least 1 dose of study drug. Mean (standard error) pain intensity scores in the tapentadol ER and oxycodone CR groups, respectively, were 7.6 (0.05) and 7.6 (0.11) at baseline and decreased to 4.4 (0.09) and 4.5 (0.17) at endpoint. The overall incidence of TEAEs was 85.7% in the tapentadol ER group and 90.6% in the oxycodone CR group. In the tapentadol ER and oxycodone CR groups, respectively, TEAEs led to discontinuation in 22.1% and 36.8% of patients; gastrointestinal TEAEs led to discontinuation in 8.6% and 21.5% of patients. Conclusion: Tapentadol ER (100 to 250 mg bid) was associated with better gastrointestinal tolerability than oxycodone HCl CR (20 to 50 mg bid) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year.
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- 2010
10. Efficacy and Safety of Tapentadol Extended Release Compared with Oxycodone Controlled Release for the Management of Moderate to Severe Chronic Pain Related to Osteoarthritis of the Knee
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Mila Etropolski, Akiko Okamoto, Bernd Lange, Juergen Haeussler, Christine Rauschkolb, A. Steup, Marc Afilalo, Ilse Van Hove, Brigitte Kuperwasser, and Kathy Kelly
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Male ,Analgesic ,Pain ,Osteoarthritis ,Placebo ,law.invention ,Double-Blind Method ,Phenols ,Randomized controlled trial ,law ,Humans ,Medicine ,Pharmacology (medical) ,Aged ,Analgesics ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Tapentadol ,Knee pain ,Delayed-Action Preparations ,Anesthesia ,Chronic Disease ,Female ,medicine.symptom ,business ,Oxycodone ,medicine.drug - Abstract
Background: Tapentadol is a novel, centrally acting analgesic with μ-opioid receptor agonist and norepinephrine reuptake inhibitor activity. Objective: To evaluate the efficacy and safety of tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain. Methods: This was a randomized, double-blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received tapentadol ER, oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive tapentadol ER 100–250 mg twice daily, oxycodone HCl CR 20–50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation. Results: Efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], −0.7 [−1.04, −0.33]), and throughout the maintenance period (−0.7 [−1.00, −0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], −0.3 [−0.67, −0.00]) but not at week 12 (−0.3 [−0.68, 0.02]). A significantly higher percentage of patients achieved ≥50% improvement in pain intensity in the tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved ≥50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342). Conclusion: Treatment with tapentadol ER 100–250 mg twice daily or oxycodone HCl CR 20–50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with tapentadol ER than with oxycodone CR. [Trial registration number: NCT00421928 (ClinicalTrials.gov Identifier)]
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- 2010
11. Dose Conversion Between Tapentadol Immediate and Extended Release for Low Back Pain
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Akiko Okamoto, Christine Rauschkolb, Mila Etropolski, and Douglas Y. Shapiro
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business.industry ,Analgesic ,Tapentadol ,Crossover study ,Low back pain ,Equianalgesic ,Acetaminophen ,law.invention ,Anesthesiology and Pain Medicine ,Randomized controlled trial ,law ,Anesthesia ,Clinical endpoint ,Medicine ,medicine.symptom ,business ,medicine.drug - Abstract
Background: Tapentadol, a novel, centrally acting analgesic with 2 mechanisms of action (µopioid receptor agonism and norepinephrine reuptake inhibition), has been developed in an immediate-release (IR) and an extended-release (ER) formulation. Determination of the safety and equianalgesic ratios for conversion between formulations is important for physicians with patients taking tapentadol IR who may want to switch to tapentadol ER, or vice versa, for any reason. Objectives: To test whether the total daily dose (TDD) of tapentadol IR may be directly converted into a comparable TDD of tapentadol ER, and vice versa, with equivalent efficacy and comparable safety. Study Design: Randomized, double-blind, 2-period (2 weeks each) crossover study. Setting: Study centers (N = 13) in the United States. Methods: Patients with moderate to severe chronic low back pain received tapentadol IR 50, 75, or 100 mg every 4 or 6 hours (maximum TDD, 500 mg) during the 3-week open-label period to identify an optimal, stable dose of tapentadol IR for each patient. Patients were then randomized in a 1:1 ratio to receive, during the first 2-week double-blind period, either the optimal dose of tapentadol IR identified during the open-label period or a TDD of tapentadol ER (100, 150, 200, or 250 mg bid) that was as close as possible to the TDD of tapentadol IR from the open-label period. During a subsequent, 2-week double-blind period, patients received whichever formulation was not received during the first double-blind period. The primary endpoint was the mean average daily pain intensity (on an 11-point numerical rating scale) during the last 3 days of each double-blind treatment period. If the 95% confidence intervals (CIs) of the least squares mean difference between formulations were within the range of −2 to 2, the formulations were considered equivalent. Results: Of the 88 patients who were randomized, 72 completed both double-blind treatments, and 60 were included in the per-protocol analysis. The mean (standard deviation [SD]) pain intensity score decreased from 7.3 (1.19) pre-treatment to 4.2 (2.13) after 3 weeks of open-label treatment with tapentadol IR and remained constant throughout double-blind treatment (3.9 or 4.0 each week) for both formulations. The mean (SD) of the average pain intensity scores over the last 3 days of double-blind treatment was 3.9 (2.17) with tapentadol IR and 4.0 (2.29) with tapentadol ER, for an estimated difference of 0.1 (95% CI, −0.09 to 0.28). For both tapentadol IR and tapentadol ER, the median TDD administered was 300.0 mg, and acetaminophen was used by 39.5% and 45.2% of patients, respectively. The incidence of treatment-emergent adverse events during double-blind treatment was similar between the tapentadol IR and tapentadol ER groups. Limitations: Use of rescue medication theoretically could have influenced pain measurements, but in practice, pain measurements did not differ between treatments. Conclusions: Approximately equivalent TDDs of tapentadol IR and tapentadol ER provided equivalent analgesic efficacy for the relief of moderate to severe chronic low back pain and were similarly well tolerated, allowing for direct conversion between the 2 formulations. Key words: Chronic low back pain, conversion, efficacy, equivalence, extended release, immediate release, opioid, safety, tapentadol
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- 2010
12. Long-term Safety and Efficacy of Tapentadol Extended Release Following up to 2 Years of Treatment in Patients With Moderate to Severe, Chronic Pain: Results of an Open-label Extension Trial
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C. Rauschkolb, Stephen A. Rappaport, Robert Buynak, Kevin Rod, Fabian Heisig, Pierre Arsenault, and Mila Etropolski
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Male ,Population ,Phenols ,medicine ,Humans ,Pharmacology (medical) ,education ,Aged ,Pharmacology ,education.field_of_study ,Cross-Over Studies ,business.industry ,Chronic pain ,Middle Aged ,Osteoarthritis, Knee ,Tapentadol ,medicine.disease ,Low back pain ,Crossover study ,Knee pain ,Tolerability ,Anesthesia ,Delayed-Action Preparations ,Chronic Disease ,Quality of Life ,Female ,medicine.symptom ,Chronic Pain ,business ,Oxycodone ,Low Back Pain ,medicine.drug - Abstract
Purpose Tapentadol extended release (ER) has demonstrated efficacy and safety for the management of moderate to severe, chronic pain in adults. This study evaluated the long-term safety and tolerability of tapentadol ER in patients with chronic osteoarthritis or low back pain. Methods Patients were enrolled in this 1-year, open-label extension study after completing one of two 15-week, placebo-controlled studies of tapentadol ER and oxycodone controlled release (CR) for osteoarthritis knee pain (NCT00421928) or low back pain (NCT00449176), a 7-week crossover study between tapentadol immediate release and tapentadol ER for low back pain (NCT00594516), or a 1-year safety study of tapentadol ER and oxycodone CR for osteoarthritis or low back pain (NCT00361504). After titrating the drug to an optimal dose, patients received tapentadol ER (100–250 mg BID) for up to 1 year (after finishing treatment in the preceding studies); patients who were previously treated with tapentadol ER in the 1-year safety study received tapentadol ER continuously for up to 2 years in total. Findings Of the 1,154 patients in the safety population, 82.7% were aged >65 years and 57.9% were female; 50.1% had mild baseline pain intensity. Mean (SD) pain intensity scores (11-point numerical rating scale) were 3.9 (2.38) at baseline (end of preceding study) and 3.7 (2.42) at end point, indicating that pain relief was maintained during the extension study. Improvements in measures of quality of life (eg, EuroQol-5 Dimension and the 36-item Short Form Health Survey [SF-36]) health status questionnaires) achieved during the preceding studies were maintained during the open-label extension study. Tapentadol ER was associated with a safety and tolerability profile comparable to that observed in the preceding studies. The most common treatment-emergent adverse events (incidence ≥10%; n=1154) were headache (13.1%), nausea (11.8%), and constipation (11.1%). Similar efficacy and tolerability results were shown for patients who received up to 2 years of tapentadol ER treatment. Implications Pain relief and improvements in quality of life achieved during the preceding studies were maintained throughout this extension study, during which tapentadol ER was well tolerated for the long-term treatment of chronic osteoarthritis or low back pain over up to 2 years of treatment. (ClinicalTrials.gov identifier: NCT00487435.)
- Published
- 2014
13. Ready conversion of patients with well-controlled, moderate to severe, chronic malignant tumor-related pain on other opioids to tapentadol extended release
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Keiichiro Hirose, Mila Etropolski, Yushin Tominaga, Hiroki Ohashi, Keiichiro Imanaka, and Taka Matsumura
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Male ,Analgesic ,Phenols ,Neoplasms ,medicine ,Humans ,Pharmacology (medical) ,Original Research Article ,Neoplasm Metastasis ,Aged ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,medicine.disease ,Tapentadol ,Analgesics, Opioid ,Treatment Outcome ,Tolerability ,Opioid ,Anesthesia ,Delayed-Action Preparations ,Chronic Disease ,Morphine ,Female ,Chronic Pain ,Cancer pain ,business ,Oxycodone ,medicine.drug - Abstract
Background and Objectives The effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50–250 mg twice daily) from previous around-the-clock strong opioid therapy in patients with moderate to severe, chronic malignant tumor–related cancer pain that was well-controlled. Methods This randomized, open-label, phase III study, which was conducted in Japan, included a 1- to 2-week screening period (on previous opioid) and an 8-week, open-label treatment period. Eligible patients, who were taking a strong opioid analgesic and had a mean pain intensity score
- Published
- 2014
14. Adverse event reporting in the recent study by Imanaka et al. describing the efficacy and safety of tapentadol extended release for tumor-related pain
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Keiichiro Hirose, Mikio Wanibe, Keiichiro Imanaka, Masaki Ohsaka, Taka Matsumura, Ilse Van Hove, Yushin Tominaga, and Mila Etropolski
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Male ,medicine.medical_specialty ,Study drug ,business.industry ,Incidence (epidemiology) ,Disease progression ,Phases of clinical research ,General Medicine ,Tapentadol ,Phenols ,Internal medicine ,Anesthesia ,Neoplasms ,medicine ,Humans ,Pain Management ,Female ,Extended release ,Chronic Pain ,business ,Adverse effect ,Oxycodone ,medicine.drug - Abstract
This letter is intended to provide additional clarification for your readers regarding the potentially confusing issue of adverse event vs serious adverse event reporting in a recently published phase 3 study of tapentadol extended release (ER) for malignant tumor-related pain. The results of a randomized, double-blind, phase 3 study evaluating the efficacy and safety of tapentadol ER for the management of moderate-tosevere, chronic malignant tumor-related pain were published in this journal in October 2013 in our article entitled, ‘Efficacy and safety of oral tapentadol extended release in Japanese and Korean patients with moderate-to-severe, chronic malignant tumor-related pain’. According to our company’s policy and in accordance with guidance from the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, all treatment-emergent adverse events (TEAEs) were recorded throughout the double-blind treatment and for 3 days after the last dose of the study drug (based on the half-life of tapentadol ER), while any spontaneously reported serious AEs were recorded for up to 30 days after the last dose of the study drug. This difference in the time periods for collecting and reporting of TEAEs vs serious AEs resulted in an apparent discrepancy in the percentage of patients experiencing disease progression. The incidence of disease progression reported in Table 4 (which lists the most common [incidence 5%] TEAEs overall) was 21.4% (36/168) with tapentadol ER and 19.2% (33/172) with oxycodone controlled release (CR), while the incidence of disease progression given in the first full paragraph beneath Table 4, which was based on serious AE reporting (which included an additional 30 day reporting period after the last dose of study drug), was 23.8% (40/168) with tapentadol ER and 20.9% (36/172) with oxycodone CR.
- Published
- 2014
15. Tapentadol immediate release versus oxycodone immediate release for treatment of acute low back pain
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Carmela Benson, Christine Rauschkolb, Bruce L. Moskovitz, Mila Etropolski, David M. Biondi, and Jim Xiang
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Adult ,Male ,Time Factors ,Adolescent ,Nausea ,Analgesic ,Population ,law.invention ,Young Adult ,Drug Delivery Systems ,Randomized controlled trial ,Double-Blind Method ,Phenols ,law ,Outpatients ,medicine ,Humans ,Adverse effect ,education ,Aged ,Pain Measurement ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,Tapentadol ,Acute Pain ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,Tolerability ,Anesthesia ,Female ,medicine.symptom ,business ,Oxycodone ,Low Back Pain ,medicine.drug - Abstract
Background: Tapentadol has demonstrated analgesic efficacy across a range of pain conditions. Objective: In a head-to-head study of up to 10 days in duration, the analgesic efficacy and tolerability of tapentadol immediate release (IR) versus oxycodone IR using a flexible dosing regimen were compared in patients with acute low back pain (LBP) and associated radicular leg pain. Study Design: Randomized (1:1), double-blind, parallel-group study (NCT00986180). Independent Ethics Committee/Institutional Review Board approval of the protocol was obtained. Setting: Ninety US outpatient treatment centers. Methods: Patients with moderate to severe, acute LBP received tapentadol IR (50, 75, or 100 mg) or oxycodone HCl IR (5, 10, or 15 mg) every 4 to 6 hours as needed for pain for up to 10 days. Patients reported current pain intensity twice daily (11-point numerical rating scale). The primary efficacy endpoint was the sum of pain intensity differences (SPID) over 120 hours for LBP. Tapentadol IR was considered non-inferior to oxycodone IR if the upper bound of the 95% confidence interval (CI) for the least-squares mean (LSM) difference in SPID120 was less than 120. Secondary efficacy endpoints included 2-, 3-, and 10-day SPID for LBP; 2-, 3-, 5-, and 10-day SPID for index leg pain; 30% and 50% responder rates; patient and clinician global impressions of change; and patient satisfaction. Results: The safety population included 645 patients, and the modified intent-to-treat population included 585 patients. In the tapentadol IR and oxycodone IR groups, respectively, 86.3% (277/321) and 82.7% (268/324) of patients completed the study. The most common reason for study withdrawal in both treatment groups was adverse events (tapentadol IR, 6.5% [21/321]; oxycodone IR, 7.1% [23/324]). The LSM (standard error) SPID120 for LBP was 264.6 (11.43) for tapentadol IR (n = 287) and 264.0 (11.22) for oxycodone IR (n = 298). The 95% CI for the LSM difference was −32.1 to 30.9; therefore, tapentadol IR was non-inferior to oxycodone IR for relief of LBP. No significant differences were observed between tapentadol IR and oxycodone IR for other SPID endpoints or for responder rates. At the end of the study, in the tapentadol IR and oxycodone IR treatment groups, respectively, approximately two-thirds of patients (66.2% vs 66.2%) and clinicians (67.9% vs 66.6%) rated patients’ overall condition as “very much improved” or “much improved,” and more than 75% of patients (79.3% vs 78.9%) were “very satisfied” or “somewhat satisfied” with their treatment. In the tapentadol IR and oxycodone IR groups, respectively, 52.3% (168/321) and 58.0% (188/324) of patients reported at least one treatment-emergent adverse event (TEAE); the most common (≥ 10%) TEAEs were vomiting (15.9% vs 24.7%), nausea (15.9% vs 20.7%), and dizziness (11.8% vs 10.5%). Vomiting (odds ratio [95% CI], 1.74 [1.17 - 2.57]) and constipation (3.43 [1.45 - 8.11]) were significantly more likely to occur in the oxycodone IR treatment group. Two (0.6%) patients in the tapentadol IR group and 3 (0.9%) patients in the oxycodone IR group experienced treatment-emergent serious adverse events. Limitations: Strict patient monitoring is generally not representative of real-world medical practice; consequently, higher incidences of TEAEs may have been reported than would be expected in a typical practice setting; it is anticipated that this bias would be similar for both treatment groups. Conclusions: This head-to-head study demonstrated that tapentadol IR had comparable analgesic efficacy and overall safety to that of oxycodone IR for the relief of moderate to severe, acute LBP and associated radicular leg pain when using flexible dosing regimens that reflect typical use in clinical practice; however, tapentadol IR demonstrated a better gastrointestinal tolerability profile, particularly for the common opioid-related TEAEs of vomiting and constipation. Clinical Trial Registration: NCT00986180 Key words: Tapentadol, oxycodone, acute low back pain, radicular leg pain, neuropathic pain, flexible dosing, radiculopathy, gastrointestinal tolerability
- Published
- 2013
16. A pooled analysis of patient-specific factors and efficacy and tolerability of tapentadol extended release treatment for moderate to severe chronic pain
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Bernd Lange, Jutta Goldberg, Dipl.-Stat. Achim Steup, Mila Etropolski, and Christine Rauschkolb
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Male ,Placebo ,Body Mass Index ,Double-Blind Method ,Phenols ,Osteoarthritis ,Medicine ,Humans ,Pharmacology (medical) ,Analgesics ,business.industry ,Chronic pain ,General Medicine ,medicine.disease ,Tapentadol ,Low back pain ,Anesthesiology and Pain Medicine ,Knee pain ,Opioid ,Tolerability ,Anesthesia ,Delayed-Action Preparations ,Female ,medicine.symptom ,Chronic Pain ,business ,Oxycodone ,Low Back Pain ,medicine.drug - Abstract
Objective: To evaluate via retrospective analysis the efficacy and tolerability of tapentadol extended release (ER; 100-250 mg bid) based on patient-specific factors, including baseline pain intensity, prior opioid experience, gender, and body mass index (BMI). Design: Data were pooled from three randomized, double-blind phase III studies of similar design that evaluated the efficacy and tolerability of tapentadol ER for the management of moderate to severe, chronic osteoarthritis knee pain (NCT00421928, NCT00486811) or low back pain (NCT00449176). Setting: In the original trials, patients were recruited at primary, secondary, and tertiary care centers, institutional settings, and private practices in North America, Europe, Australia, and New Zealand. Patients: Data were analyzed separately for groups of patients divided by baseline pain intensity, prior opioid experience, gender, and BMI. Interventions: Patients received twice-daily placebo, tapentadol ER (100-250 mg), or oxycodone HCl controlled release (CR; 20-50 mg) for a 3-week titration and 12-week maintenance period. Main outcome measures: Changes from baseline in average pain intensity (11-point numerical rating scale) at week 12 of the maintenance period and for the overall maintenance period. Results: Efficacy and tolerability were evaluated in 2,968 and 2,974 patients, respectively. The efficacy of tapentadol ER was shown in subpopulations divided by baseline pain intensity, prior opioid experience, gender, and BMI. Tapentadol ER was also shown to be well tolerated and associated with better gastrointestinal tolerability than oxycodone CR in the evaluated subpopulations (divided by prior opioid experience and gender). Conclusions: Results suggest that tapentadol ER (100-250 mg bid) provides similar pain relief and tolerability, regardless of baseline pain intensity, prior opioid experience, gender, or BMI.
- Published
- 2012
17. Composite measure to assess efficacy/gastrointestinal tolerability of tapentadol ER versus oxycodone CR for chronic pain: pooled analysis of randomized studies
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David Provenzano, Kai Fai Ho, PharmD Samir H. Mody, Sanjay Merchant, and Mila Etropolski
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Adult ,Male ,Nausea ,Gastrointestinal Diseases ,Chemistry, Pharmaceutical ,Risk Assessment ,Phenols ,Risk Factors ,Surveys and Questionnaires ,Odds Ratio ,Medicine ,Humans ,Multicenter Studies as Topic ,Pharmacology (medical) ,Aged ,Pain Measurement ,Randomized Controlled Trials as Topic ,Analysis of Variance ,Chi-Square Distribution ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,medicine.disease ,Tapentadol ,Low back pain ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,Knee pain ,Logistic Models ,Treatment Outcome ,Opioid ,Tolerability ,Clinical Trials, Phase III as Topic ,Anesthesia ,Delayed-Action Preparations ,Female ,medicine.symptom ,Chronic Pain ,business ,Oxycodone ,medicine.drug - Abstract
Objective: To evaluate a composite measure for chronic pain that balances pain relief with tolerability. Design: Post hoc meta-analysis of three randomized, multicenter, double-blind studies. Participants: Subjects with moderate-to-severe chronic osteoarthritis knee pain or low back pain who had been randomized to receive active treatment with tapentadol extended release (ER; n = 978) or oxycodone controlled release (CR; n = 999). Twenty-two subjects were excluded, mainly because they did not receive treatment. Main outcome measures: We defined the composite measure as GTE 30 percent pain relief without nausea/vomiting/constipation and without discontinuations (GTE 30 percent PRT [pain relief/tolerability]). We also considered GTE 50 percent PRT as well as GTE 30 percent and GTE 50 percent pain relief without any adverse events of any type. To further evaluate GTE 30 percent PRT, we studied its relationship with four patient-reported outcomes: EQ-5D, Physical and Mental Component Summaries of SF-36, Patient Global Impression of Change, and Patient Assessment of Constipation Symptoms. Results: At week 12, tapentadol ER recipients were more likely to have GTE 30 percent PRT than oxycodone CR recipients (OR, 3.15; 95% CI, 2.47, 4.00; p < 0.001). Significant differences were also observed with the other three composite measures (p < 0.001). At week 12, subjects with GTE 30 percent PRT had more favorable changes in all patient-reported outcomes than those without and were more likely to have threshold changes in EQ-5D and SF-36 (all p < 0.001). Conclusions: Tapentadol ER was associated with significantly better composite outcomes than oxycodone CR. Because both pain relief and gastrointestinal tolerability appeared to be related to outcomes, the composite measure may represent a useful tool for comparing opioids that merits further evaluation. Keywords: chronic pain, gastrointestinal tolerability, composite measure, opioid, oxycodone, tapentadol DOI:10.5055/jom.2013.0147
- Published
- 2012
18. Pharmacokinetic evaluation of tapentadol extended-release tablets in healthy subjects
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Mila Etropolski, Vera Hillewaert, Birger Wenge, Peter Zannikos, Johan W. Smit, and Hans-Jürgen Stahlberg
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Adult ,Male ,Metabolic Clearance Rate ,Administration, Oral ,Bioequivalence ,Drug Administration Schedule ,law.invention ,Eating ,Young Adult ,Pharmacokinetics ,Randomized controlled trial ,Japan ,Phenols ,law ,Medicine ,Humans ,Pharmacology (medical) ,Dosing ,Netherlands ,Meal ,Cross-Over Studies ,business.industry ,Half-life ,General Medicine ,Middle Aged ,Tapentadol ,Crossover study ,Healthy Volunteers ,United States ,Analgesics, Opioid ,Anesthesiology and Pain Medicine ,Therapeutic Equivalency ,Anesthesia ,Area Under Curve ,Delayed-Action Preparations ,Female ,business ,medicine.drug ,Half-Life ,Tablets - Abstract
Objective: To evaluate serum pharmacokinetics of tapentadol administered to healthy subjects as extended-release (ER) tablets. Design: Seven single-dose studies (five randomized, crossover, bioequivalence studies; a study in Japanese men; and a randomized, crossover, effects-of-food study) and one repeated-dose study. Setting: Clinical research settings in the United States and The Netherlands. Patients or participants: Healthy males and females were enrolled into seven studies; one study enrolled only Japanese males. Interventions: In the bioequivalence studies, subjects first received one polyethylene oxide- or hypromellose-based tapentadol ER tablet (50, 100, 150, 200, or 250 mg; one dose per study), then (after washout) the other formulation (matching dose). In all other studies, subjects received polyethylene oxide-based tapentadol ER tablets. In the repeated-dose study, subjects received one 250 mg tablet, then (after washout) one 250 mg tablet every 12 hours (five doses). In the food-effect study, subjects received one 250 mg tablet within 30 minutes after a high-fat meal or after 10 hours of fasting. In the study in Japanese men, subjects received one 100 mg tablet. Main outcome measures: Maximum tapentadol concentrations (C max ) were typically observed 5 hours after dosing. Mean terminal half-life values ranged from 4.4 to 5.9 hours. Tapentadol C max and AUC values increased proportionally following single ER (polyethylene oxide-based tablets) doses of 50 to 250 mg. Trough tapentadol concentrations increased during repeat dosing until reaching steady-state by the third dose. Serum C max and area under the concentration-time curve (AUC) values at steady state were 1.6 and 1.9 times higher relative to singledose administration. Coadministration of the 250 mg dose with a high-fat meal increased C max and AUC values by an average of < 17 percent. Conclusions: The pharmacokinetics of tapentadol ER are consistent after repeated and single-dose administration. Tapentadol ER may be administered without regard to food intake. No clinically significant differences were observed in the pharmacokinetics of tapentadol between Japanese and Caucasian subjects.
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- 2012
19. Pharmacokinetic and pharmacodynamic modeling of opioid-induced gastrointestinal side effects in patients receiving tapentadol IR and oxycodone IR
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Rachel Lin, Partha Nandy, David Upmalis, Akiko Okamoto, Xu Steven Xu, and Mila Etropolski
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Male ,Analgesic ,Population ,Receptors, Opioid, mu ,Pharmaceutical Science ,Pharmacology ,Pharmacokinetics ,Phenols ,medicine ,Humans ,Pharmacology (medical) ,education ,Proportional Hazards Models ,education.field_of_study ,business.industry ,Organic Chemistry ,Middle Aged ,Tapentadol ,Gastrointestinal Tract ,Opioid ,Oxymorphone ,Anesthesia ,Pharmacodynamics ,Molecular Medicine ,Female ,business ,Oxycodone ,Biotechnology ,medicine.drug - Abstract
To understand the relationship between the risk of opioid-related gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone as well as its active metabolite, oxymorphone, using pharmacokinetic/pharmacodynamic models. The analysis was based on a study in patients with moderate-to-severe pain following bunionectomy. Population PK modeling was conducted to estimate population PK parameters for tapentadol, oxycodone, and oxymorphone. Time to AEs was analyzed using Cox proportional-hazards models. Risk of nausea, vomiting, and constipation significantly increased with exposure to tapentadol or oxycodone/oxymorphone. However, elevated risk per drug exposure of AEs for tapentadol was ~3–4 times lower than that of oxycodone, while elevated AE risk per drug exposure of oxycodone was ~60 times lower than that for oxymorphone, consistent with reported in vitro receptor binding affinities for these compounds. Simulations show that AE incidence following administration of tapentadol IR is lower than that following oxycodone IR intake within the investigated range of analgesic noninferiority dose ratios. This PK/PD analysis supports the clinical findings of reduced nausea, vomiting and constipation reported by patients treated with tapentadol, compared to patients treated with oxycodone.
- Published
- 2012
20. Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride
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Mila Etropolski, Kathleen Kelly, Akiko Okamoto, and Christine Rauschkolb
- Subjects
Male ,Constipation ,Vomiting ,Pain ,law.invention ,Randomized controlled trial ,Double-Blind Method ,Phenols ,law ,Oxycodone hydrochloride ,Medicine ,Humans ,Pharmacology (medical) ,Bowel function ,Aged ,Dose-Response Relationship, Drug ,business.industry ,Chronic pain ,Nausea ,General Medicine ,Middle Aged ,Tapentadol ,medicine.disease ,Gastrointestinal tolerability ,Equianalgesic ,Analgesics, Opioid ,Anesthesia ,Chronic Disease ,Female ,medicine.symptom ,Joint Diseases ,business ,Oxycodone ,medicine.drug - Abstract
Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR's improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo).Oxycodone HCl IR treatment significantly decreased (P0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations.Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.
- Published
- 2011
21. 334 ASSESSMENT OF OPIOIDWITHDRAWAL IN PATIENTS TREATED WITH TAPENTADOL PROLONGED RELEASE DURING AN OPEN-LABEL EXTENSION STUDY
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Brigitte Kuperwasser, Thomas Häufel, R. Lange, Mila Etropolski, Judy Ashworth, and Bernd Lange
- Subjects
Rheumatology ,Prolonged release ,business.industry ,Extension study ,Anesthesia ,medicine ,Biomedical Engineering ,In patient ,Orthopedics and Sports Medicine ,Open label ,Tapentadol ,business ,medicine.drug - Published
- 2010
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22. A thorough QT/QTc study of multiple doses of tapentadol immediate release in healthy subjects
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C. Rauschkolb, D Upmalis, Jens Rengelshausen, S S Wang, C. Oh, Mila Etropolski, T. Häufel, and B Mangold
- Subjects
Adult ,Male ,Nausea ,Receptors, Opioid, mu ,Placebo ,QT interval ,Electrocardiography ,Double-Blind Method ,Phenols ,Heart rate ,Medicine ,Humans ,Pharmacology (medical) ,Aged ,Pharmacology ,Analgesics ,Cross-Over Studies ,business.industry ,Middle Aged ,Tapentadol ,Crossover study ,Confidence interval ,Anesthesia ,Female ,medicine.symptom ,business ,Blood sampling ,medicine.drug - Abstract
This randomized, double-blind, placebo- and positive-controlled 4-way crossover study evaluated the effects of tapentadol immediate release (IR) on the QT/QTc interval.Healthy subjects received tapentadol IR 100 mg or 150 mg, or placebo, every 6 h on Days 1 and 2, with a= 7-day washout between treatments. Moxifloxacin 400 mg was the positive control. Serial triplicate 12-lead electrocardiograms (ECGs) were performed; the Fridericia correction (QTcF) was the primary correction method. Serial blood sampling was performed for pharmacokinetic analyses.Of the 75 subjects who were randomized, 68 received at least 1 dose of study medication, and 59 completed the study. Upper limits of the 90% confidence intervals (CIs) for the difference in mean DeltaQTcF between tapentadol IR 100 or 150 mg and placebo were10 ms (non-inferiority criterion) for all time points. The lower limit of the 90% CI for mean DeltaQTcF between moxifloxacin and placebo exceeded 5 ms from 1 to 6 h after dosing, establishing assay sensitivity. No subject had a postdose QTc interval480 ms, change from baseline60 ms, or clinically relevant change in heart rate or other ECG variables. Steady-state concentrations were reached within 18 to 24 h. Common adverse events were vertigo (central nervous system (CNS) origin), headache, somnolence, nausea, vomiting, and feeling drunk.Therapeutic and supratherapeutic doses of tapentadol do not affect the QT/QTc interval.
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- 2010
23. Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study
- Author
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Mila Etropolski, Robert Buynak, Claudia Lange, Bernd Lange, Christine Rauschkolb, A. Steup, Ilse Van Hove, Akiko Okamoto, and D.Y. Shapiro
- Subjects
Adult ,Male ,Analgesic ,Receptors, Opioid, mu ,Placebo ,law.invention ,Placebos ,Randomized controlled trial ,Double-Blind Method ,Phenols ,law ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Aged ,Pharmacology ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,medicine.disease ,Tapentadol ,Low back pain ,Opioid ,Anesthesia ,Delayed-Action Preparations ,Female ,medicine.symptom ,business ,Oxycodone ,Low Back Pain ,medicine.drug - Abstract
To evaluate the efficacy and safety of tapentadol extended release (ER) for the management of moderate to severe chronic low back pain.Patients (N = 981) were randomized 1:1:1 to receive tapentadol ER 100 - 250 mg b.i.d., oxycodone HCl controlled release (CR) 20 - 50 mg b.i.d., or placebo over 15 weeks (3-week titration period, 12-week maintenance period).Efficacy was assessed as change from baseline in average pain intensity (11-point NRS) at week 12 of the maintenance period and throughout the maintenance period; last observation carried forward was used to impute missing pain scores. Adverse events (AEs) were monitored throughout the study.Tapentadol ER significantly reduced average pain intensity versus placebo at week 12 (least squares mean difference vs placebo [95% confidence interval], -0.8 [-1.22, -0.47]; p0.001) and throughout the maintenance period (-0.7 [-1.06,-0.35]; p0.001). Oxycodone CR significantly reduced average pain intensity versus placebo at week 12 (-0.9 [-1.24,-0.49]; p0.001) and throughout the maintenance period (-0.8 [-1.16,-0.46]; p0.001). Tapentadol ER was associated with a lower incidence of treatment-emergent AEs (TEAEs) than oxycodone CR. Gastrointestinal TEAEs, including constipation, nausea, and vomiting, were among the most commonly reported TEAEs (placebo, 26.3%; tapentadol ER, 43.7%; oxycodone CR, 61.9%). The odds of experiencing constipation or the composite of nausea and/or vomiting were significantly lower with tapentadol ER than with oxycodone CR (both p0.001).Tapentadol ER (100 - 250 mg b.i.d.) effectively relieved moderate to severe chronic low back pain over 15 weeks and had better gastrointestinal tolerability than oxycodone HCl CR (20 - 50 mg b.i.d.).
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- 2010
24. Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain
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Bernd Lange, Judy Ashworth, A. Steup, Akiko Okamoto, Brigitte Kuperwasser, Mila Etropolski, and Thomas Häufel
- Subjects
Male ,Osteoarthritis ,Kaplan-Meier Estimate ,Placebo ,Severity of Illness Index ,Double-Blind Method ,Phenols ,medicine ,Oxycodone hydrochloride ,Humans ,Pharmacology (medical) ,Least-Squares Analysis ,Aged ,Pain Measurement ,Randomized Controlled Trials as Topic ,Analysis of Variance ,business.industry ,Chronic pain ,General Medicine ,Middle Aged ,Osteoarthritis, Knee ,medicine.disease ,Tapentadol ,Low back pain ,Analgesics, Opioid ,Treatment Outcome ,Tolerability ,Clinical Trials, Phase III as Topic ,Anesthesia ,Delayed-Action Preparations ,Chronic Disease ,Quality of Life ,Female ,medicine.symptom ,Safety ,business ,Oxycodone ,Low Back Pain ,medicine.drug - Abstract
This pooled analysis of data from three phase 3 studies in patients with chronic osteoarthritis knee or low back pain evaluated the efficacy and tolerability of tapentadol prolonged release (PR; 100–250 mg twice daily) compared with placebo and oxycodone hydrochloride (HCl) controlled release (CR; 20–50 mg twice daily). Patients in each study were randomized to receive twice-daily doses of placebo, tapentadol PR (100–250 mg), or oxycodone HCl CR (20–50 mg) for a 12-week maintenance period, preceded by a 3-week titration period. Primary endpoints were change from baseline in average pain intensity (11-point numeric rating scale) at week 12 of the maintenance period and for the overall maintenance period using last observation carried forward for imputation of values missing after treatment discontinuation. A total of 2968 patients were evaluated for efficacy; 2974 patients were evaluated for safety. Compared with placebo, treatment with tapentadol PR or oxycodone CR resulted in significantly greater reductions in pain intensity from baseline at week 12 and for the overall maintenance period (all P
- Published
- 2010
25. 708 RESULTS OF A RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐AND ACTIVE‐CONTROLLED TRIAL OF TAPENTADOL EXTENDED RELEASE FOR CHRONIC LOW BACK PAIN
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Mila Etropolski, A. Steup, I. Van Hove, Bernd Lange, T. Häufel, Akiko Okamoto, D.Y. Shapiro, and Robert Buynak
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business.industry ,Placebo ,Tapentadol ,law.invention ,Chronic low back pain ,Double blind ,Anesthesiology and Pain Medicine ,Randomized controlled trial ,law ,Anesthesia ,Medicine ,Extended release ,business ,medicine.drug - Published
- 2009
26. 707 ANALYSIS OF EFFICACY AND SAFETY OF TAPENTADOL EXTENDED RELEASE (ER) FOR CHRONIC LOW BACK PAIN BASED ON PRIOR OPIOID EXPERIENCE
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I. Van Hove, Akiko Okamoto, Claudia Lange, D.Y. Shapiro, Mila Etropolski, H. Leslie, and Juergen Haeussler
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medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Opioid ,business.industry ,Anesthesia ,medicine ,Extended release ,Tapentadol ,business ,medicine.drug ,Chronic low back pain ,Surgery - Published
- 2009
27. 709 EFFICACY AND SAFETY OF TAPENTADOL EXTENDED RELEASE (ER) IN PATIENTS WITH DIABETIC PERIPHERAL NEUROPATHIC PAIN: RESULTS OF A RANDOMIZED‐WITHDRAWAL STUDY
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S. Schwartz, D.Y. Shapiro, Christine Rauschkolb, Akiko Okamoto, Mila Etropolski, and Juergen Haeussler
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Anesthesiology and Pain Medicine ,business.industry ,Anesthesia ,Medicine ,In patient ,Extended release ,business ,Tapentadol ,Peripheral neuropathic pain ,medicine.drug - Published
- 2009
28. F644 AN ANALYSIS OF CHANGES IN VITAL SIGNS AND ELECTROCARDIOGRAM MEASUREMENTS WITH TAPENTADOL PROLONGED RELEASE (PR) TREATMENT
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J. Goldberg, D. Koch, D.Y. Shapiro, Mila Etropolski, and Akiko Okamoto
- Subjects
Anesthesiology and Pain Medicine ,business.industry ,Prolonged release ,Anesthesia ,Vital signs ,Medicine ,business ,Tapentadol ,medicine.drug - Published
- 2011
29. 333 SHORT FORM-36 (SF-36) AND EUROQOL-5 DIMENSION (EQ-5D) RESULTS FROM RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDIES OF TAPENTADOL PROLONGED RELEASE (PR) IN PATIENTS WITH MODERATE TO SEVERE CHRONIC NOCICEPTIVE AND NEUROPATHIC PAIN
- Author
-
R. Lange, Mila Etropolski, B. Lange, Akiko Okamoto, Judy Ashworth, and A. Greene
- Subjects
SF-36 ,business.industry ,Biomedical Engineering ,Tapentadol ,Double blind ,Nociception ,Rheumatology ,Prolonged release ,EQ-5D ,Anesthesia ,Neuropathic pain ,medicine ,Orthopedics and Sports Medicine ,In patient ,business ,medicine.drug - Published
- 2010
30. 188. Gastrointestinal Tolerability of Tapentadol Extended Release Treatment for Chronic Low Back Pain
- Author
-
D.Y. Shapiro, Mila Etropolski, Thomas Haeufel, Akiko Okamoto, Ilse Van Hove, and Harvey Leslie
- Subjects
business.industry ,Anesthesia ,medicine ,Surgery ,Orthopedics and Sports Medicine ,Neurology (clinical) ,Extended release ,Tapentadol ,Gastrointestinal tolerability ,business ,medicine.drug ,Chronic low back pain - Published
- 2009
31. Poster 51: Health-related Outcomes Associated With Tapentadol Extended Release and Oxycodone Controlled Release Treatment for Chronic Low Back or Osteoarthritis Pain: Results of a Randomized, Open-label, Phase 3 Long-term Safety Trial
- Author
-
Robert Lange, Jane S. Gilbert, Achim Steup, Alison Greene, Bettyanne McCann, Mila Etropolski, Claudia Lange, and Brigitte Kuperwasser
- Subjects
medicine.medical_specialty ,business.industry ,Rehabilitation ,Health related ,Physical Therapy, Sports Therapy and Rehabilitation ,Osteoarthritis ,Tapentadol ,medicine.disease ,Low back pain ,Controlled release ,Neurology ,Anesthesia ,medicine ,Physical therapy ,Neurology (clinical) ,Long term safety ,Open label ,medicine.symptom ,business ,Oxycodone ,medicine.drug - Published
- 2009
32. Sensitivity analyses of the primary efficacy endpoint in a randomized-withdrawal phase 3 trial of tapentadol extended release (ER) in patients with painful diabetic peripheral neuropathy (DPN)
- Author
-
Juergen Haeussler, D.Y. Shapiro, A. Steup, Mila Etropolski, and Akiko Okamoto
- Subjects
business.industry ,Endocrinology, Diabetes and Metabolism ,General Medicine ,medicine.disease ,Tapentadol ,Endocrinology ,Peripheral neuropathy ,Anesthesia ,Internal Medicine ,Medicine ,In patient ,Extended release ,business ,Sensitivity analyses ,medicine.drug - Published
- 2009
33. Efficacy and tolerability of tapentadol extended release (ER) in patients with chronic, painful diabetic peripheral neuropathy (DPN): results of a phase 3, randomized-withdrawal, placebo-controlled study
- Author
-
K. Karcher, D.Y. Shapiro, B. Lange, C. Rauschkolb-Löffler, D. Pennett, A. Vinik, and Mila Etropolski
- Subjects
business.industry ,Placebo-controlled study ,medicine.disease ,Tapentadol ,Anesthesiology and Pain Medicine ,Peripheral neuropathy ,Neurology ,Tolerability ,Anesthesia ,medicine ,In patient ,Neurology (clinical) ,Extended release ,business ,medicine.drug - Published
- 2012
34. A post hoc pooled data analysis to evaluate blood pressure (BP) and heart rate (HR) measurements in patients with a current or prior history of hypertension who received tapentadol ER, oxycodone CR, or placebo in chronic pain studies
- Author
-
Jim Xiang, Mila Etropolski, Bruce L. Moskovitz, and David M. Biondi
- Subjects
business.industry ,Chronic pain ,Tapentadol ,medicine.disease ,Placebo ,Anesthesiology and Pain Medicine ,Blood pressure ,Neurology ,Anesthesia ,Heart rate ,Medicine ,Pooled data ,In patient ,Neurology (clinical) ,business ,Oxycodone ,medicine.drug - Published
- 2011
35. 337 HEALTH STATUS OF PATIENTS WHO RECEIVED TAPENTADOL PROLONGED RELEASE DURING AN OPEN-LABEL EXTENSION STUDY
- Author
-
Robert Lange, E. McCann, Mila Etropolski, I. Van Hove, Brigitte Kuperwasser, and T. Häufel
- Subjects
medicine.medical_specialty ,business.industry ,Extension study ,Biomedical Engineering ,Tapentadol ,Surgery ,Rheumatology ,Prolonged release ,Anesthesia ,medicine ,Orthopedics and Sports Medicine ,Open label ,business ,medicine.drug - Published
- 2010
36. Tapentadol extended release (ER) versus oxycodone controlled release (CR) for management of chronic low back or osteoarthritis pain: analyses of study discontinuations due to constipation, nausea, or vomiting
- Author
-
David M. Biondi, G. Vorsanger, Jim Xiang, R. Lange, Bruce L. Moskovitz, and Mila Etropolski
- Subjects
medicine.medical_specialty ,Constipation ,Nausea ,business.industry ,Osteoarthritis ,medicine.disease ,Tapentadol ,Controlled release ,Surgery ,Anesthesiology and Pain Medicine ,Neurology ,Anesthesia ,medicine ,Vomiting ,Neurology (clinical) ,medicine.symptom ,business ,Oxycodone ,Low back ,medicine.drug - Published
- 2010
37. Tapentadol extended release (ER) versus oxycodone controlled release (CR) for management of chronic low back or osteoarthritis pain: influence of prior opioid experience on study discontinuations due to constipation, nausea, or vomiting
- Author
-
G. Vorsanger, David M. Biondi, J. Ashworth, Mila Etropolski, Bruce L. Moskovitz, and Jim Xiang
- Subjects
Constipation ,Nausea ,business.industry ,Osteoarthritis ,medicine.disease ,Tapentadol ,Controlled release ,Anesthesiology and Pain Medicine ,Neurology ,Opioid ,Anesthesia ,medicine ,Vomiting ,Neurology (clinical) ,medicine.symptom ,business ,Oxycodone ,medicine.drug - Published
- 2010
38. 292 TAPENTADOL PROLONGED RELEASE (PR) FOR PAINFUL DIABETIC PERIPHERAL NEUROPATHY (DPN): EFFICACY AND SAFETY BY PRIOR OPIOID EXPERIENCE AND DOSE CATEGORY
- Author
-
Akiko Okamoto, Bernd Lange, Christine Rauschkolb, A. Steup, D.Y. Shapiro, and Mila Etropolski
- Subjects
Anesthesiology and Pain Medicine ,Peripheral neuropathy ,Opioid ,Prolonged release ,business.industry ,Anesthesia ,medicine ,Tapentadol ,business ,medicine.disease ,medicine.drug - Published
- 2010
39. 502 PATIENT GLOBAL IMPRESSION OF CHANGE ASSOCIATED WITH TAPENTADOL PROLONGED RELEASE (PR) FOR THE MANAGEMENT OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY (DPN)
- Author
-
Mila Etropolski, Robert Lange, A. Steup, Akiko Okamoto, and D.Y. Shapiro
- Subjects
medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Peripheral neuropathy ,Prolonged release ,business.industry ,Anesthesia ,medicine ,medicine.disease ,business ,Tapentadol ,Surgery ,medicine.drug - Published
- 2010
40. Safety and tolerability of tapentadol extended release (ER) versus oxycodone controlled release (CR) in elderly patients with chronic low back or osteoarthritis pain
- Author
-
G. Vorsanger, R. Lange, Mila Etropolski, David M. Biondi, B. Moskovit, and Jim Xiang
- Subjects
medicine.medical_specialty ,business.industry ,Osteoarthritis ,Tapentadol ,medicine.disease ,Controlled release ,Surgery ,Anesthesiology and Pain Medicine ,Neurology ,Tolerability ,Anesthesia ,medicine ,Neurology (clinical) ,Extended release ,business ,Oxycodone ,Low back ,medicine.drug - Published
- 2010
41. 291 TAPENTADOL PROLONGED RELEASE (PR) FOR THE MANAGEMENT OF PAINFUL DIABETIC PERIPHERAL NEUROPATHY: BRIEF PAIN INVENTORY ASSESSMENTS
- Author
-
Robert Lange, D.Y. Shapiro, Christine Rauschkolb, S. Schwartz, A. Steup, Mila Etropolski, Juergen Haeussler, and Akiko Okamoto
- Subjects
medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Peripheral neuropathy ,business.industry ,Prolonged release ,Anesthesia ,medicine ,Brief Pain Inventory ,medicine.disease ,Tapentadol ,business ,Surgery ,medicine.drug - Published
- 2010
42. P141. Tapentadol Extended Release vs. Oxycodone Controlled Release for Treating Moderate to Severe Chronic Low Back Pain: Study Discontinuations from a Randomized, Double-Blind Phase 3 Trial
- Author
-
Ilse Van Hove, D.Y. Shapiro, Bernd Lange, Christine Rauschkolb, Claudia Lange, Mila Etropolski, and Akiko Okamoto
- Subjects
Moderate to severe ,business.industry ,Tapentadol ,Controlled release ,Chronic low back pain ,Double blind ,Anesthesia ,Medicine ,Surgery ,Orthopedics and Sports Medicine ,Neurology (clinical) ,Extended release ,business ,Oxycodone ,medicine.drug - Published
- 2009
43. 328 EFFICACY AND SAFETY OF TAPENTADOL EXTENDED RELEASE VERSUS OXYCODONE CONTROLLED RELEASE IN OPIOID-NAIVE AND OPIOID-EXPERIENCED PATIENTS WITH CHRONIC PAIN ASSOCIATED WITH OSTEOARTHRITIS OF THE KNEE
- Author
-
A. Steup, Akiko Okamoto, J. Häussler, Kathleen Kelly, Mila Etropolski, I. Van Hove, B. Lange, Brigitte Kuperwasser, and Horst Weber
- Subjects
business.industry ,Biomedical Engineering ,Chronic pain ,Opioid naive ,Osteoarthritis ,medicine.disease ,Tapentadol ,Controlled release ,Rheumatology ,Opioid ,Anesthesia ,medicine ,Orthopedics and Sports Medicine ,Extended release ,business ,Oxycodone ,medicine.drug - Published
- 2009
44. 334 INCIDENCE AND SEVERITY OF GASTROINTESTINAL TREATMENT-EMERGENT ADVERSE EVENTS IN PATIENTS TREATED WITH TAPENTADOL EXTENDED RELEASE (ER) OR OXYCODONE CONTROLLED RELEASE (CR) FOR RELIEF OF CHRONIC OSTEOARTHRITIS KNEE PAIN
- Author
-
F. Laschewski, C. Rauschkolb, Akiko Okamoto, A. Steup, Brigitte Kuperwasser, Mila Etropolski, T. Häufel, I. Van Hove, and Kathleen Kelly
- Subjects
business.industry ,Incidence (epidemiology) ,Biomedical Engineering ,macromolecular substances ,Tapentadol ,Controlled release ,Knee pain ,Rheumatology ,Anesthesia ,Medicine ,Orthopedics and Sports Medicine ,In patient ,Extended release ,medicine.symptom ,business ,Adverse effect ,Oxycodone ,medicine.drug - Published
- 2009
45. Poster 66: Tapentadol Extended Release for the Relief of Chronic Pain Associated With Osteoarthritis of the Knee: Assessment of Opioid Withdrawal From a Randomized, Active- and Placebo-controlled Study
- Author
-
Thomas Häufel, Mila Etropolski, Ilse Van Hove, Brigitte Kuperwasser, Akiko Okamoto, Christine Rauschkolb, and Kathleen Kelly
- Subjects
medicine.medical_specialty ,Opioid withdrawal ,business.industry ,Rehabilitation ,Chronic pain ,Placebo-controlled study ,Physical Therapy, Sports Therapy and Rehabilitation ,Osteoarthritis ,medicine.disease ,Tapentadol ,Neurology ,Anesthesia ,medicine ,Physical therapy ,Neurology (clinical) ,Extended release ,business ,medicine.drug - Published
- 2009
46. Poster 48: Gastrointestinal Tolerability of Tapentadol Extended Release in Patients With Chronic Low Back Pain: Results of a Randomized, Double-blind, Active- and Placebo-controlled Phase 3 Study
- Author
-
Claudia Lange, Ilse Van Hove, Mila Etropolski, Robert Buynak, D.Y. Shapiro, and Akiko Okamoto
- Subjects
medicine.medical_specialty ,business.industry ,Rehabilitation ,Phases of clinical research ,Physical Therapy, Sports Therapy and Rehabilitation ,Gastrointestinal tolerability ,Placebo ,Tapentadol ,Low back pain ,Chronic low back pain ,Surgery ,Double blind ,Neurology ,Anesthesia ,medicine ,In patient ,Neurology (clinical) ,medicine.symptom ,business ,medicine.drug - Published
- 2009
47. Efficacy, safety, and gastrointestinal tolerability of tapentadol ER in a randomized, double-blind, placebo- and active-controlled phase III study of patients with chronic low back pain
- Author
-
D.Y. Shapiro, Mila Etropolski, Robert Buynak, Claudia Lange, and Akiko Okamoto
- Subjects
Double blind ,Anesthesiology and Pain Medicine ,Neurology ,business.industry ,Anesthesia ,medicine ,Neurology (clinical) ,Tapentadol ,business ,Gastrointestinal tolerability ,Placebo ,medicine.drug ,Chronic low back pain - Published
- 2009
48. Health status (EuroQol-5 Dimension [EQ-5D]) in patients with painful diabetic peripheral neuropathy (DPN) treated with tapentadol extended release (ER): results of a randomized-withdrawal phase 3 study
- Author
-
R. Lange, Akiko Okamoto, Mila Etropolski, D.Y. Shapiro, and Bernd Lange
- Subjects
Nausea ,business.industry ,Endocrinology, Diabetes and Metabolism ,Chronic pain ,General Medicine ,medicine.disease ,Tapentadol ,Endocrinology ,Peripheral neuropathy ,EQ-5D ,Anesthesia ,Internal Medicine ,medicine ,Clinical endpoint ,medicine.symptom ,Adverse effect ,business ,Somnolence ,medicine.drug - Abstract
245 -0.6), WOCF (-1.1), PMI (-0.6), modified BOCF (-0.8), and OC for patients who completed treatment (-1.0). The most frequently reported treatment-emergent adverse events were nausea, dizziness, and somnolence in the OL phase, and nausea, anxiety, and diarrhea in the tapentadol ER group in the DB phase. conclusion: Significant improvement in the primary endpoint was demonstrated with all imputation methods used, indicating that the efficacy of tapentadol ER was robust in this study of patients with moderate to severe chronic pain related to DPN. Complications nerve Conflict of interest Employee: ME, DYS, AO, and JH are employees of Johnson & Johnson. AS is an employee of Grunenthal GmbH.
- Published
- 2009
49. Health-related outcomes associated with tapentadol extended release (ER) treatment for the management of painful diabetic peripheral neuropathy (DPN): results of a randomized-withdrawal phase 3 trial
- Author
-
Akiko Okamoto, D.Y. Shapiro, Mila Etropolski, Christine Rauschkolb, R. Lange, and R. Kleinert
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,digestive, oral, and skin physiology ,food and beverages ,Health related ,Blood lipids ,General Medicine ,Type 2 diabetes ,medicine.disease ,Tapentadol ,Gastroenterology ,Endocrinology ,Peripheral neuropathy ,Internal medicine ,Anesthesia ,Internal Medicine ,Medicine ,Extended release ,business ,Glycemic ,medicine.drug - Abstract
193 (P>0.05) and -0.05±0.06 HbA1c (P>0.05). Significant differences were also seen between nuts and muffins with greater falls on nuts for LDL-C (-0.19±0.12 mmol/L, P=0.03). Nut intake directly related to change in LDL-C (r= -.24, n=98, P
- Published
- 2009
50. Dose patterns in commercially insured subjects chronically exposed to opioids: a large cohort study in the United States
- Author
-
Amy Matcho, Maria Soledad Cepeda, Mila Etropolski, Rachel Weinstein, Daniel Fife, and Raymond C. Boston
- Subjects
Agonist ,Medicine(all) ,Pathology ,medicine.medical_specialty ,Percentile ,Palliative care ,business.industry ,medicine.drug_class ,lcsh:RC952-1245 ,lcsh:Special situations and conditions ,Cancer ,Retrospective cohort study ,General Medicine ,medicine.disease ,Opioid ,Interquartile range ,Anesthesia ,medicine ,Morphine ,business ,Research Article ,medicine.drug - Abstract
Background Little data exist on how opioid doses vary with the length of exposure among chronic opioid users. Methods To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95th percentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated. Results Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25th, 50th, and 75th percentile of dose was stable during the first 2 years of use, but the 95th percentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point. Conclusions Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.
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