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Background: The incidence and mortality of colorectal cancer (CRC) increase with age and, therefore, it is recommended that adults undergo regular CRC screening, ideally by colonoscopy, with some new guidelines recommending screening begin at 45 years. Effective bowel preparation is a critical step to a successful colonoscopy. Of concern is that older adults may have poorer quality of bowel preparation or reduced tolerability for the bowel preparation. Here, we performed a post hoc secondary analysis for the effect of age on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation. Methods: A phase III, randomized, assessor-blinded, multicenter, non-inferiority study was conducted comparing split-dose, low-volume SPMC oral solution with split-dose, low-volume sodium picosulfate, magnesium oxide, and citric acid powder for oral solution. A post hoc secondary analysis was performed to assess efficacy, safety, and tolerability of SPMC oral solution by age group (Results: Within age groups, at least 83.9% of participants were responders by the AS, and at least 91.1% of participants were responders by the BBPS in the right colon. On both scales, responder rates were highest in the youngest age group and decreased with increasing age. Greater than 88% of participants in any age group found the preparation ‘easy’ or ‘acceptable’ to ingest, with rates of ‘easy’ being highest in the oldest age group. No new safety signals were seen in any age group. The most commonly reported drug-related, treatment-emergent AEs were, by ascending age group, nausea (7.0%, 3.2%, 0.8%), headache (4.2%, 2.8%, 1.6%) and vomiting (2.8%, 1.2%, 0.8%). Conclusion: Ready-to-drink SPMC oral solution showed good efficacy of overall colon cleansing and tolerability in adults across different age groups, including those ⩾65 years. ClinicalTrials.gov identifier: NCT03017235.

Naomi C Sacks,1,2 Abhishek Sharma,1 Philip L Cyr,1,3 Gerald Bertiger,4 David N Dahdal,5 Stuart P Brogadir5 1Precision Xtract, Boston, MA, USA; 2Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 3College of Health and Human Services, University of North Carolina, Charlotte, NC, USA; 4Hillmont GI, Flourtown, PA, USA; 5Ferring Pharmaceuticals Inc., Parsippany, NJ, USA Background and aims: Proper bowel cleansing is necessary prior to colonoscopy, but poor tolerability to bowel preparation agents may increase the odds of poor cleansing and incomplete screenings. The aim of this study was to evaluate the real-world effectiveness and safety of bowel preparation agents. Methods: Claims data were extracted for individuals who had a screening colonoscopy from July 1, 2012, to June 30, 2015, were ≥18 years of age, and who could be observed ≥6 months before and ≥3 months after the screening. Data were stratified by agent class, including over-the-counter (OTC), low-volume (LV), and high-volume (HV) agents. Rates of incomplete screenings, repeat screenings, and hospitalizations were reported. Multivariate logistic regression was conducted to compare outcomes for sodium picosulfate, magnesium oxide, and citric acid (P/MC) vs other agents. Results: Of 2.8 million individuals, 71.5% were average risk and 28.5% were high risk for colorectal cancer. Rates of use were 2.8% for P/MC, 30.1% for other LV agents, 9.4% for HV agents, and 56.6% for OTC agents. All individuals who used P/MC had significantly lower odds of incomplete screenings compared to those who used other LV agents or HV agents (P

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the United States. Colonoscopy is widely preferred for CRC screening and is the most commonly used method in the United States. Adequate bowel preparation is essential for successful colonoscopy CRC screening. However, up to one-quarter of colonoscopies are associated with inadequate bowel preparation, which may result in reduced polyp and adenoma detection rates, unsuccessful screens, and an increased likelihood of repeat procedure. In addition, standardized criteria and assessment scales for bowel preparation quality are lacking. While several bowel preparation quality scales are referred to in the literature, these differ greatly in grading methodology and categorization criteria. Published reliability and validity data are available for five bowel preparation quality assessment scales, which vary in several key attributes. However, clinicians and researchers continue to use a variety of bowel preparation quality measures, including nonvalidated scales, leading to potential confusion and difficulty when comparing quality results among clinicians and across clinical trials. Optimal clinical criteria for bowel preparation quality remain controversial. The use of validated bowel preparation quality scales with stringent but simple scoring criteria would help clarify clinical trial data as well as the performance of colonoscopy in clinical practice related to quality measurements.

Background:We performed a post hoc secondary analysis for the effect of body mass index (BMI) on the efficacy, tolerability, and safety of ready-to-drink sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) bowel preparation.Methods:A phase III, randomized, assessor-blinded, multicenter, noninferiority study was conducted comparing split-dose, low-volume SPMC oral solution with a powder formulation for oral solution. A post hoc secondary analysis assessed efficacy, safety, and tolerability of SPMC oral solution stratified by BMI. BMI was classified by Centers for Disease Control and Prevention definitions (underweight and normal weight: BMI 2; overweight: BMI 25–29.9 kg/m2; class I obesity: BMI 30–34.9 kg/m2; class II obesity: BMI 35–39.9 kg/m2; class III/severe obesity: BMI ⩾40 kg/m2). Prespecified primary efficacy endpoint (‘responders’) was the proportion of participants with ‘excellent’ or ‘good’ ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of cleansing of the right colon as assessed by the Boston Bowel Preparation Scale (BBPS); as well as selected findings from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs) and laboratory evaluations.Results:Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation ‘easy’ or ‘acceptable’ to ingest, and the majority (>58%) rated SPMC oral solution as ‘better’ than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%).Conclusions:Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups.ClinicalTrials.gov Registration:NCT03017235

Background New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. Objective This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). Design Multicenter, assessor-blinded, randomized, noninferiority study. Setting University hospitals, academic medical centers, and private clinics across the United States. Patients Adults preparing for colonoscopy. Interventions P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. Main Outcome Measurements This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. Results The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets ( P Limitations Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. Conclusions The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets.

Gerald Bertiger,1 Edward Jones,2 David N Dahdal,3 Dennis C Marshall,3 Raymond E Joseph3 1Hillmont GI, Flourtown, PA, USA; 2Delaware Valley Nephrology and Hypertension Associates, Philadelphia, PA, USA; 3Ferring Pharmaceuticals Inc., Parsippany, NJ, USA Background: We performed a post hoc analysis of two clinical trials to assess whether sodium picosulfate and magnesium (Mg2+) citrate (Prepopik® [P/MC]), a dual-action bowel preparation for colonoscopy, has an impact on serum Mg2+ levels and cardiac electrophysiology. Although rare, hypermagnesemia has been reported in patients consuming Mg2+-containing cathartics, especially patients who are elderly and have renal impairment. Methods: Data were analyzed from two prospective, Phase III, randomized, assessor-blinded, active-control, multicenter, pivotal studies that investigated split-dose/day-before P/MC. Serum Mg2+ and creatinine clearance (CrCl) were measured at screening, on the day of colonoscopy, and 24–48 hours, 7 days, and 4 weeks after colonoscopy; electrocardiograms also were obtained at these time points. Results: In total, 304 patients received split-dose P/MC and 294 patients received day-before P/MC. Only 10% of the patients had serum Mg2+ above the upper limit of normal (1.05 mmol/L) on the day of colonoscopy. There was a slight inverse correlation between CrCl and Mg2+ levels on the day of colonoscopy; however, even at the lowest CrCl, serum Mg2+ remained below clinically significant levels of 2.0 mmol/L. Increases in serum Mg2+ were transient, with levels returning to baseline within 24–48 hours, regardless of renal function. No patients with elevated Mg2+ experienced a corrected QT (QTc) interval >500 milliseconds or a QTc interval increase of ≥60 milliseconds from baseline. P/MC had no impact on PR or QRS interval. Conclusion: P/MC produces little impact on serum Mg2+ levels with no clinically significant effect on cardiac conduction in patients, including those with mild-to-moderate renal impairment. Keywords: bowel preparation, hypermagnesemia, renal impairment, sodium picosulfate

The purpose of this study was to determine the intrinsic functions of the feline pylorus in vitro. The myoelectric and pressure characteristics of the intact pylorus, antrum, and duodenum, free of extrinsic hormonal or neural influences, were studied in an in vitro bath that allowed separation of the bathing medium surrounding the different bowel segments. Basal recordings revealed a zone of tonic high pressure of 28.4 +/- 3.5 mmHg (mean +/- SEM) at the pylorus. The basal slow wave frequencies in the pylorus and duodenum were 2.8 +/- 1.4 and 12.6 +/- 0.6 cycles/min, respectively. Spontaneous action potential-associated phasic contractions of the pylorus were noted in 38% of preparations. Enteric nerve stimulation with direct electric current (10 Hz, 1 ms, 10-50 V) applied proximal to the pylorus gave relaxation of the pylorus at the lower voltages and rebound excitation at higher voltages. Electrical stimulation distal to the pylorus yielded phasic contractile pyloric response during the entire stimulus. The duodenal instillation of 0.5 N HCl produced action potential-associated phasic contractions of the pylorus and duodenum but not the antrum. Pyloric responses to electrical stimulation or acidification were abolished by tetrodotoxin (10(-5) M). Bethanechol (10(-6) M) or substance P (10(-7) M) produced a contractile response at the site of stimulation but this response was not transmitted to include adjacent bowel segments. These studies suggest that the pyloric sphincter with its intrinsic reflex properties can be studied in vitro.

An in vitro whole organ bath preparation was used to examine the effects of leucine enkephalin on the cat ileocecal sphincter (ICS) intraluminal pressure and myoelectric activity. The bath allowed separation of the bathing media surrounding the ICS and the ileum. Leucine enkephalin (2 × 10 −7 M) when added to the ileal bathing medium caused a delayed increase in ICS spike activity and pressure which was blocked by tetrodotoxin (10 −5 M). In contrast, leucine enkephalin (2 × 10 −7 M) added directly to the ICS bathing medium caused an immediate spike-associated contractile response which was tetrodotoxin-resistant. Thus both an indirect and direct opiate action at the ICS was demonstrated.