Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo‐controlled trials in adults with severe constipation

Abstract

AbstractBackgroundPatients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS‐C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS‐C with severe constipation.MethodsData were analyzed post hoc from randomized, placebo‐controlled trials (CIC [n = 2], IBS‐C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5‐point scale) or ≥8.0 (IBS‐C; 11‐point scale) during a 2‐week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS‐C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks).Key ResultsSevere constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS‐C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS‐C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS‐C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both).Conclusions and InferencesPlecanatide was effective in the treatment of severe constipation in adults with CIC or IBS‐C.