Efficacy, safety, and tolerability of a ready-to-drink bowel preparation in overweight and obese adults: subanalysis by body mass index from a phase III, assessor-blinded study.

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 < 25 kg/m2; 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. CLINICALTRIALSGOV REGISTRATION: NCT03017235.

Efficacy, safety, and tolerability of a ready-to-drink bowel preparation: subanalysis by age from a phase III, assessor-blinded study.

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 (<50 years, 50-64 years, ⩾65 years). The 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: 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.

Efficacy and safety of a ready-to-drink bowel preparation for colonoscopy: a randomized, controlled, non-inferiority trial.

BACKGROUND: We performed a randomized, controlled, assessor-blinded, multicenter, non-inferiority (NI) study to compare the safety and efficacy of a ready-to-drink formulation of sodium picosulfate, magnesium oxide, and citric acid (SPMC oral solution) with a powder formulation (P/MC powder) for oral solution. METHODS: Eligible participants (adults undergoing elective colonoscopy) were randomized 1:1 to split-dose SPMC oral solution or P/MC powder. The primary efficacy endpoint assessed overall colon-cleansing quality with the Aronchick Scale (AS), and the key secondary efficacy endpoint rated quality of right colon cleansing with the Boston Bowel Preparation Scale (BBPS). Assessments were performed by a treatment-blinded endoscopist. Tolerability was assessed using the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events and laboratory evaluations. RESULTS: The study included 901 participants: 448 for SPMC oral solution; 453 for P/MC powder. SPMC oral solution demonstrated non-inferiority to P/MC powder {87.7% (393/448) responders versus 81.5% (369/453) responders [difference (95% confidence interval): 6.3% (1.8, 10.9)]}. The key secondary efficacy objective assessing the right colon was also met. According to the prespecified hierarchical testing, after meeting the primary and key secondary objectives, SPMC oral solution was tested for superiority to P/MC powder for the primary endpoint (p = 0.0067). SPMC oral solution was well tolerated. Most common adverse events were nausea (3.1% versus 2.9%), headache (2.7% versus 3.1%), hypermagnesemia (2.0% versus 5.1%), and vomiting (1.3% versus 0.7%) for SPMC oral solution and P/MC powder, respectively. CONCLUSIONS: Ready-to-drink SPMC oral solution showed superior efficacy of overall colon cleansing compared with P/MC powder, with similar safety and tolerability.[ClinicalTrials.gov identifier: NCT03017235.].

Real-world comparison of the effectiveness and safety of different bowel preparation agents.

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<0.05). In average-risk patients, rates of 30- and 90-day repeat screenings were highest for the P/MC group (16.7% and 23.0%, respectively) compared to other agents. Across all patient analysis groups, the rates of hospitalizations for hyponatremia or dehydration were much higher for those who used an OTC bowel preparation agent compared to those who used LV or HV agents, or P/MC. CONCLUSION: P/MC was associated with lower rates of incomplete colonoscopy and higher rates of repeat screenings, suggesting it was better tolerated than other agents. OTC agents were associated with higher rates of hospitalizations.

Bowel preparation quality scales for colonoscopy.

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.

Serum magnesium concentrations in patients receiving sodium picosulfate and magnesium citrate bowel preparation: an assessment of renal function and electrocardiographic conduction.

BACKGROUND: We performed a post hoc analysis of two clinical trials to assess whether sodium picosulfate and magnesium (Mg(2+)) citrate (Prepopik(®) [P/MC]), a dual-action bowel preparation for colonoscopy, has an impact on serum Mg(2+) levels and cardiac electrophysiology. Although rare, hypermagnesemia has been reported in patients consuming Mg(2+)-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 Mg(2+) 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 Mg(2+) above the upper limit of normal (1.05 mmol/L) on the day of colonoscopy. There was a slight inverse correlation between CrCl and Mg(2+) levels on the day of colonoscopy; however, even at the lowest CrCl, serum Mg(2+) remained below clinically significant levels of 2.0 mmol/L. Increases in serum Mg(2+) were transient, with levels returning to baseline within 24-48 hours, regardless of renal function. No patients with elevated Mg(2+) 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 Mg(2+) levels with no clinically significant effect on cardiac conduction in patients, including those with mild-to-moderate renal impairment.

Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.

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 < .0001). 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.