Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials

Darren M Brenner; Spencer D Dorn; Ronald P Fogel; Jennifer Christie; Adam P Laitman; Jonathan Rosenberg

doi:10.2147/IJGM.S400431

Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials

Int J Gen Med. 2023 Aug 25:16:3769-3777. doi: 10.2147/IJGM.S400431. eCollection 2023.

Authors

Darren M Brenner¹, Spencer D Dorn², Ronald P Fogel³, Jennifer Christie⁴, Adam P Laitman⁵, Jonathan Rosenberg⁶

Affiliations

¹ Internal Medicine-Gastroenterology, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA.
² Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA.
³ Digestive Health Center of Michigan, Chesterfield, MI, USA.
⁴ Emory University School of Medicine, Atlanta, GA, USA.
⁵ Salix Pharmaceuticals, Bridgewater, NJ, USA.
⁶ GI Alliance of Illinois, Gurnee, IL, USA.

Abstract

Purpose: Patients with irritable bowel syndrome with constipation (IBS-C) experience abdominal pain with altered bowel movements. Plecanatide is indicated as IBS-C treatment in adults. This integrated analysis further characterizes plecanatide efficacy and safety in IBS-C.

Patients and methods: Data pooled from 2 identically designed phase 3 trials included adults with IBS-C randomized to plecanatide 3 mg or 6 mg, or placebo once daily for 12 weeks. A daily diary recorded stool frequency/symptoms, with abdominal pain, bloating, cramping, discomfort, fullness, and straining intensity individually rated. Overall response (primary endpoint) was defined as ≥30% improvement from baseline in average worst abdominal pain severity and increase of ≥1 complete spontaneous bowel movement, during same week (composite), for ≥6 of 12 weeks. Secondary endpoints included sustained response (overall response, plus meeting weekly composite criteria during ≥2 of last 4 treatment weeks) and changes from baseline in individual symptoms. Safety assessments included adverse event monitoring.

Results: Overall, 2176 patients (74.0% female; mean [SD] age, 43.5 [14.1] years) were included in efficacy analyses (plecanatide 3 mg [n = 724], 6 mg [n = 723], placebo [n = 729]). A significantly greater percentage of patients achieved overall response with plecanatide 3 mg (25.6%) and 6 mg (26.7%) versus placebo (16.0%; both P < 0.001 vs placebo). A significantly greater percentage of patients were sustained responders with plecanatide 3 mg (24.3%) and 6 mg (25.6%) versus placebo (15.6%; both P < 0.001 vs placebo). Significant improvements from baseline in abdominal discomfort, abdominal fullness, abdominal pain, bloating, and cramping occurred as early as Week 1 (Week 2 for abdominal pain) with plecanatide and were maintained through Week 12 versus placebo. Diarrhea, the most common adverse event, occurred in 4.3% (3 mg), 4.0% (6 mg) and 1.0% (placebo) of patients, leading to study discontinuation in 1.2%, 1.4%, and 0 patients, respectively.

Conclusion: Plecanatide is safe and effective for treating global and individual IBS-C symptoms.

Keywords: abdominal pain; bloating; functional GI disorders; guanylate cyclase-C agonist; irritable bowel syndrome.

Grants and funding

The trials were supported by Synergy Pharmaceuticals, and the current analyses were supported by Salix Pharmaceuticals.