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ITCA 650 consists of a small titanium osmotic mini-pump that is subdermally placed in the abdominal wall during a brief office procedure. As an investigational product for the treatment of type 2 diabetes (T2D), ITCA 650 provides a continuous subcutaneous infusion of exenatide over 3 or 6 months. An integrated analysis of efficacy and safety was conducted from 2 double-blind, randomized, Phase 3 studies, which evaluated pooled data with ITCA 650 20/60 mcg/d vs. placebo or sitagliptin for the treatment of patients with T2D, inadequately controlled on antidiabetic drugs. The efficacy endpoints were mean change from baseline at Week 39 for HbA1c, body weight, composite endpoints of HbA1c and weight loss, and proportion achieving HbA1c Disclosure L.L. Kjems: Employee; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. P. Prabhakar: None. B. Schwartz: Employee; Self; Intarcia Therapeutics, Inc.. H. Huang: None. M.A. Baron: Employee; Self; Intarcia Therapeutics, Inc..

ITCA 650 consists of a small titanium osmotic mini—pump that is subdermally placed in the abdominal wall during a brief in-office procedure. As an investigational product for the treatment of type 2 diabetes (T2D), ITCA 650 provides a continuous subcutaneous infusion of exenatide over 3 or 6 months. Pooled 39-week data from two double-blind, randomized, Phase 3 studies were used to evaluate the efficacy of ITCA 650 20/60 mcg/d in patients with T2D inadequately controlled by oral antidiabetic drugs (OADs). Results in the overall population (N=683) and in subgroups according to age, gender, BMI, ethnicity, time since diagnosis, baseline HbA1c, GI adverse events, presence of anti-drug antibodies, and renal function are reported. As shown in the Figure, the overall mean (standard deviation [SD]) reduction in HbA1c (%) was 1.5% (1.2) with clinically meaningful reductions in HbA1c consistently observed irrespective of age, gender, BMI, ethnicity, time from T2D diagnosis, eGFR and background OADs (data not shown). Patients with a higher baseline HbA1c had a greater response. Mean weight loss was 3.4 kg (SD 4.7), and 40.7% (95% CI 0.36-0.46) of patients achieved a composite endpoint of HbA1c/weight reduction of >0.5%/≥2 kg. Similar changes were likewise seen consistently across subgroups. ITCA 650 demonstrated consistent efficacy across a wide spectrum of patients with T2D. Disclosure P. Prabhakar: None. L.L. Kjems: Employee; Self; Intarcia Therapeutics, Inc.. Stock/Shareholder; Self; Intarcia Therapeutics, Inc.. H. Huang: None. B. Schwartz: Employee; Self; Intarcia Therapeutics, Inc. M.A. Baron: Employee; Self; Intarcia Therapeutics, Inc..

ITCA 650 is an investigational titanium osmotic mini pump that is subdermally placed in the abdominal wall during a brief office procedure to continuously deliver exenatide over 3 and 6-month periods and has the potential to improve medication adherence because patients do not self-administer. In this 26 week, open-label phase 3b study, 136 patients with T2D receiving liraglutide (1.2 to 1.8 mg/d) and metformin (≥1000 mg/d) were randomized to either the standard ITCA 650 dose regimen used in phase 3 trials of 20 mcg/d for 13 weeks followed by a 60 mcg/d maintenance dose (for 13 weeks in this study) or starting directly with the maintenance dose of 60 mcg/d for 26 weeks. The last injection of liraglutide occurred 2 days prior to randomization. The primary endpoint compared the incidence of nausea (N) and vomiting (V) between the two dose regimens. Switching from liraglutide to either dose regimen of ITCA 650 had a similar incidence of transient mild to moderate N/V (Table). Of note, 3 sites, which recruited 25% of the study population, accounted for 47% and 68% of the total N/V seen in the study. 4 patients discontinued due to GI AEs. Glycemic control remained stable in both groups. At Week 26, significant weight reduction was observed in both groups (p In conclusion, patients on stable liraglutide therapy can be switched to ITCA 650 60 mcg/d without the need for up-titration from a lower dose. Disclosure N. Rasouli: Consultant; Self; AstraZeneca, Intarcia Therapeutics, Inc. J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc.. S. Nakhle: None. B. Schwartz: Employee; Self; Intarcia Therapeutics, Inc.. P. Prabhakar: None. S.L. Kruger: None. H. Huang: None. M.A. Baron: Employee; Self; Intarcia Therapeutics, Inc..

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Objective: The purpose of this post hoc analysis was to compare the treatment effect size of eszopiclone 3 mg for insomnia in patients with a diagnosis of primary insomnia and in several of the psychiatric and medical conditions that are most commonly comorbid with insomnia. Method: Data were analyzed from 5 large, multicenter, randomized, double-blind, placebo-controlled studies of adult outpatients of at least 1 month duration published between 2006 and 2009. Diary-derived indices of sleep and daytime functioning and the Insomnia Severity Index were compared for patients with primary insomnia (DSM-IV-TR criteria, n = 828) and for those with insomnia comorbid with major depressive disorder (MDD, DSM-IV-TR criteria, n = 545), generalized anxiety disorder (GAD, DSM-IV-TR criteria, n = 595), perimenopause/postmenopause (Stages of Reproductive Aging Workshop criteria, n = 410), and rheumatoid arthritis (American College of Rheumatology criteria, n = 153). Cohen d effect sizes were calculated for each individual study as the between-treatment difference score divided by the pooled standard deviation. Results: Effect sizes ranged from 0.40 to 0.69 (small–medium) as early as week 1 and were maintained at 0.26–0.63 at week 4 for sleep latency, wake time after sleep onset, and total sleep time. Sleep latency and total sleep time effect sizes increased from week 1 to week 4 in the primary insomnia group. At week 4, effect sizes on all 3 parameters and the Insomnia Severity Index tended to be highest for the primary insomnia patients and tended to be lowest for patients with comorbid GAD and MDD. The effect sizes for daytime functioning were small for all insomnia patient groups. Conclusions: Eszopiclone 3 mg is an effective treatment for insomnia across 5 clinically diverse patient populations; however, magnitude of effect is mediated by underlying comorbidity and their treatments, with largest measures of effect seen in primary insomnia and lowest in MDD and GAD. These consistent results, and the fact that clinical trials were conducted in patients being treated as appropriate for their comorbid clinical conditions, support the results’ real-world generalizability and utility to clinical practice.

SummaryPurposeCurrent guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD.MethodsCOPD patients (mean FEV1 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15μg BID [n=76] or tiotropium 18μg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15μg BID and tiotropium 18μg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes.ResultsMean FEV1AUC0–24 (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values

Background:We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.Methods:Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.Results:ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p

Background Ciclesonide hydrofluoroalkane nasal aerosol (CIC-HFA) is currently in development as a potential treatment for allergic rhinitis. The objective of this study was to determine the efficacy and safety of CIC-HFA compared to placebo in subjects with perennial allergic rhinitis (PAR). Methods Subjects ≥12 years of age with a ≥2 year history of PAR were randomized in a placebo-controlled, double-blind, parallel group, multicenter study to CIC-HFA 74 μg (N = 298), CIC-HFA 148 μg (N = 505), or placebo (N = 307) QD AM for 26 weeks. Subject-reported change from baseline in the average of AM and PM reflective total nasal symptom score (rTNSS) and instantaneous total nasal symptom score (iTNSS) averaged over the first 6 weeks of treatment period were key endpoints and were calculated as a sum of the 4 individual nasal symptoms of congestion, runny nose, sneezing, and nasal itching each on a scale of 0 (no signs/symptoms evident) to 3 (severe symptoms). Change from baseline in the individual reflective and instantaneous nasal symptom scores over the first 6 weeks of treatment period were also evaluated. Treatment-emergent adverse events (TEAEs) were assessed throughout the study. Results CIC-HFA 74 μg and CIC-HFA 148 μg doses demonstrated a statistically significant improvement in rTNSS (LS mean change 0.70 & 0.54 respectively, P ≤ 0.001 for both), iTNSS (LS mean change 0.58 & 0.42 respectively, P ≤ 0.05 for both) and improvements in individual reflective and instantaneous nasal symptoms (P ≤ 0.05 for all, unadjusted for multiplicity) at 6 weeks from baseline. The overall incidence of TEAEs was low and comparable between the CIC treatment groups and placebo. The most frequently reported TEAEs (≥2% of subjects in any treatment group) were nausea, headache, sinus headache, cough, upper respiratory tract infection, instillation site discomfort, nasal discomfort, nasopharyngitis, sinusitis, oropharyngeal pain, and epistaxis. Conclusions In this study, once-daily treatment with CIC-HFA 74μg or CIC-HFA 148μg demonstrated statistically significant improvements in the nasal symptoms of PAR. Both active treatments were well tolerated.

Insomnia and generalized anxiety disorder (GAD) are prevalent disorders that may coexist.To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD.Double-blind, randomized, placebo-controlled, parallel-group, add-on therapy 10-week study.Multicenter outpatient study from July 2005 to April 2006.Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia.Patients received 10 mg of escitalopram oxolate for 10 weeks and were randomized to also receive either 3 mg of eszopiclone (n = 294) or placebo (n = 301) nightly for 8 weeks. For the last 2 weeks, eszopiclone was replaced with a single-blind placebo.Sleep, daytime functioning, psychiatric measures, and adverse events.Compared with treatment with placebo and escitalopram, treatment with eszopiclone and escitalopram resulted in significantly improved sleep and daytime functioning (P.05), with no evidence of tolerance. Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale (HAM-A) scores at each week (P.05) and at weeks 4 through 10 with the insomnia item removed. Clinical Global Impressions (CGI) of Improvement scores were improved with eszopiclone and escitalopram at every point (P.02), while CGI of Severity of Illness scores were not significantly different after week 1. The HAM-A response (63% vs 49%, respectively, P = .001) and remission (42% vs 36%, respectively, P = .09) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram, and median time to onset of anxiolytic response was significantly reduced (Por = .05). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and while treatment differences in anxiety measures were maintained, differences in sleep outcomes were not. Overall adverse event rates were 77.6% with cotherapy and 67.9% with monotherapy. The most common adverse events with cotherapy were unpleasant taste, headache, dry mouth, and somnolence.Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep, daytime functioning, anxiety, and mood in patients with insomnia and GAD.clinicaltrials.gov Identifier: NCT00235508.