University of New Mexico School of Medicine and New Mexico VA Health Care System Albuquerque, New Mexico
Christopher Chang, MD, PhD1, Kimberly Orleck, PA-C, MPH2, Reema Patel, PharmD3, Sarah Lorenzen, PhD4, Nicole Martinez de Andino, APRN5; 1University of New Mexico School of Medicine and New Mexico VA Health Care System, Albuquerque, NM; 2Atlanta Gastroenterology Associates, Atlanta, GA; 3Bausch Health US, LLC, Bridgewater Township, NJ; 4Salix Pharmaceuticals, Inc., Bridgewater Township, NJ; 5Augusta University, Augusta, GA
Introduction: Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) are bothersome functional gastrointestinal disorders. Plecanatide, a uroguanylin analog, demonstrated efficacy and safety in four studies in CIC and IBS-C. This analysis evaluates efficacy and safety of plecanatide in IBS-C and CIC stratified by intrinsic factors, genetic/physiologic variables within the patient population. Methods: Data from four randomized, double-blind, placebo-controlled phase 3 studies (CIC: NCT01982240, NCT02122471; IBS-C: NCT02387359, NCT02493452) were pooled for each disorder. Patients were randomized to placebo, plecanatide 3 mg, or plecanatide 6 mg for 12 weeks. The primary endpoint for CIC studies was the percentage of durable overall complete spontaneous bowel movement (CSBM) responders (ie, weekly responder for ≥ 9 of 12 treatment weeks, including ≥ 3 of the last 4 weeks) and for IBS-C studies was the percentage of overall responders (ie, ≥ 30% decrease in abdominal pain and increase of ≥ 1 CSBM in the same week for ≥ 6 of 12 treatment weeks). Secondary endpoints included changes in weekly CSBMs and spontaneous bowel movements (SBMs). Safety was assessed. Intrinsic factors included age (< 65, ≥ 65 years), sex (male, female), race (white, non-white), and body mass index (BMI; < 25, 25-30, ≥ 30 kg/m2). Results: Efficacy populations included 2639 patients with CIC and 2176 patients with IBS-C. Most patients were < 65 years ( > 89%), female ( > 74%), and white ( > 71%). In patients with CIC, plecanatide 3 mg resulted in a significantly greater percentage of durable overall CSBM responders in most subgroups (Figure 1). Among the IBS-C population, plecanatide 3 mg resulted in a significantly greater percentage of overall responders in patients aged < 65 years, females, whites, and all BMI subgroups (Figure 2). Increases in CSBMs and SBMs with plecanatide 3 mg were observed for most subgroups (P < 0.05 vs placebo). Plecanatide 6 mg results were similar. Across subgroups, no new safety signals were identified; diarrhea was the most common adverse event (3.8% of total CIC population; 3.1% of total IBS-C population). Discussion: Plecanatide 3 and 6 mg demonstrated at least numerically greater efficacy vs placebo regardless of age, race, sex, and BMI, with statistically significant improvements in most groups. For subgroups in which significance was not achieved, sample size limited interpretation. No new safety signals were identified.
Figure 1. Primary efficacy endpoint in the CIC population, stratified by age, sex, race, and BMI
Figure 2. Primary efficacy endpoint in the IBS-C population, stratified by age, sex, race, and BMI