S0506 Efficacy and Safety of Plecanatide in Patients With Chronic Idiopathic Constipation: Pooled Analysis of Two Phase 3 Trials Stratified by Concomitant Acid Suppression Use

Abstract

INTRODUCTION: Plecanatide, an approved treatment for chronic idiopathic constipation (CIC), replicates the pH-sensitive activity of uroguanylin in binding to guanylate cyclase-C receptors on intestinal epithelium. Since many individuals with CIC experience reflux and use concomitant acid suppression therapy, we explored the impact of concomitant acid suppressor use on the efficacy and safety of plecanatide in adults with CIC. METHODS: Data on two 12-week, randomized, double-blind, placebo-controlled phase 3 clinical trials of plecanatide were pooled and results were stratified by concomitant acid suppressor use. For each group, durable overall complete spontaneous bowel movement (CSBM) response rates, changes from baseline in bowel movement frequency, stool consistency (Bristol Stool Form Scale), and daily CIC symptom scores (Likert Scale, 0 = none to 4 = very severe) were assessed. Safety was analyzed in patients who received ≥1 dose. RESULTS: The intention-to-treat population (N = 2639) included 12.6% of patients with concomitant acid suppressor use. Patients using acid suppressors were 54.8 years (mean), vs 43.9 years in those not using acid suppressors. Gastroesophageal reflux disease was more common in patients using acid suppressors (83.1%), compared to those not on acid suppressors (6.1%). Proton pump inhibitors (PPIs) were used by 86.4% of patients using acid suppressors with omeprazole as the most common PPI (45.1%); H2 blockers were used by 17.8% of subjects with ranitidine as the most common H2 blocker (9.8%). Regardless of acid suppressor use, plecanatide-treated patients demonstrated significant improvements in the durable overall CSBM responder rates (Figure 1) and greater efficacy across almost all reported endpoints (Table 1) vs placebo, with benefits observed as early as Week 1. Comparisons between acid suppressor use groups (yes vs no) were not significantly different for plecanatide-treated patients (both doses, Table 1). Of the plecanatide-treated patients on acid suppressors, 6.4% experienced diarrhea, 1.4% discontinued due to diarrhea, and 2.3% had ≥ 1 serious adverse event (SAE), compared to 5.0% (diarrhea), 2.1% (discontinued due to diarrhea), and 1.0% (SAE) of patients not using acid suppressors. CONCLUSION: Plecanatide is a safe and effective treatment for CIC when administered with acid suppression therapy. Regardless of acid suppressor use, efficacy responses in plecanatide groups were significantly greater than placebo.Figure 1.: Percentage of Patients With Durable Overall CSBM Response Stratified by Concomitant Acid Suppressor Use (ITT).Table 1.: Change From Baseline in Bowel Movement Frequency, Stool Consistency, and CIC Symptoms in Patients With and Without Concomitant Acid Suppression Therapy (ITT)