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

Abstract

Darren M Brenner,1 Spencer D Dorn,2 Ronald P Fogel,3 Jennifer Christie,4 Adam P Laitman,5 Jonathan Rosenberg6 1Internal Medicine-Gastroenterology, Northwestern University-Feinberg School of Medicine, Chicago, IL, USA; 2Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA; 3Digestive Health Center of Michigan, Chesterfield, MI, USA; 4Emory University School of Medicine, Atlanta, GA, USA; 5Salix Pharmaceuticals, Bridgewater, NJ, USA; 6GI Alliance of Illinois, Gurnee, IL, USACorrespondence: Darren M Brenner, MD, FACG, AGAF, RFF, Northwestern Memorial Hospital/Arkes Family Pavilion, 676 N St Clair Street, Suite 1400, Chicago, IL, 60611, USA, Tel [phone], Fax [phone], Email [email protected]: 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

Keywords

• abdominal pain
• bloating
• functional gi disorders
• guanylate cyclase-c agonist
• irritable bowel syndrome