499 Plecanatide for Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome-Constipation: Analysis of Abdominal Bloating From Four Randomized Phase 3 Clinical Trials

Abstract

INTRODUCTION: Patients with chronic idiopathic constipation (CIC) or with irritable bowel syndrome with constipation (IBS-C) often report bloating. Plecanatide is an analogue of human uroguanylin, an intestinal peptide that induces fluid and ion secretion. Data from 4 large randomized, placebo-controlled trials in CIC (2 studies) or in IBS-C (2 studies) were analyzed to determine whether plecanatide improved bloating in patients with CIC or IBS-C. METHODS: Patients (N = 2683) who met modified Rome III criteria for CIC or patients (N = 2189) who met Rome III criteria for IBS-C were included in separate combined phase III intention-to-treat populations in CIC and IBS-C, respectively. Patients were randomized to placebo, plecanatide 3 mg QD, or plecanatide 6mg QD for 12 weeks. Baseline characteristics were comparable between groups within the CIC studies and within the IBS-C studies. The primary endpoint for the CIC trials was the percentage of durable overall complete spontaneous bowel movement (CSBM) responders (≥3 CSBMs plus increase of ≥1 CSBM over baseline in the same week) for ≥9 of the 12 treatment weeks, including ≥3 of the last 4 weeks. The IBS-C primary endpoint was the percentage of Overall Responders, defined as a patient who was a weekly responder (CSBM + ≥30% improvement in abdominal pain) for ≥6 of the 12 treatment weeks. Electronic diaries recorded daily symptoms of bloating (0 = none to 4 = very severe) and bowel movements. RESULTS: In patients with CIC, pooled efficacy demonstrated a significantly greater percentage of CSBM responders in each of the plecanatide groups when compared to the placebo group. Both plecanatide 3mg and 6mg resulted in a significantly greater percentage of Overall Responders than did placebo in the IBS-C studies (Table 1). In CIC or IBS-C, over the 12-week treatment period, both plecanatide treatment groups experienced a significantly greater reduction in weekly mean abdominal bloating scores compared with the placebo group (Table 2). The most common adverse event (AE) was diarrhea across all studies; discontinuation rates due to AEs including diarrhea were similar across studies (Table 3). CONCLUSION: Patients with CIC or IBS-C who received plecanatide 3 mg and 6 mg demonstrated a significantly greater percentage of responders compared to patients who received placebo. Bloating was significantly improved both in patients with CIC and IBS-C. Plecanatide treatment was associated with a low incidence of diarrhea and other AEs.