Neurogastroenterol Motil. 2023 Sep;35(9):e14632. doi: 10.1111/nmo.14632. Epub 2023 Jun 18.

Brooks D Cash ¹, Amol Sharma ², Anna Walker ², Adam P Laitman ³, Lin Chang ⁴

Author information

¹Division of Gastroenterology, Hepatology, and Nutrition, University of Texas Health Science Center, Houston, Texas, USA.

²Division of Gastroenterology & Hepatology, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.

³Salix Pharmaceuticals, Bridgewater, New Jersey, USA.

⁴Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California, USA.

Abstract

Background: Patients 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.

Methods: Data 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 results: Severe 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 inferences: Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.