Dartmouth-Hitchcock Health Lebanon, NH, United States
Eric Shah, MD, MBA1, William D. Chey, MD, FACG2, Alfred Nelson, MD3, Sarah Lorenzen, PhD4, Brian E. Lacy, MD, PhD, FACG3 1Dartmouth-Hitchcock Health, Lebanon, NH; 2Michigan Bowel Control Program, University of Michigan, Ann Arbor, MI; 3Mayo Clinic, Jacksonville, FL; 4Salix Pharmaceuticals, Bridgewater Township, NJ
Introduction: Chronic idiopathic constipation (CIC) is a common and bothersome functional gastrointestinal disorder. Plecanatide, a uroguanylin analog, demonstrated efficacy and safety in two studies in CIC. We evaluated the time to achieve the first weekly clinical response and durability of weekly response in patients with CIC receiving plecanatide vs. placebo.
Methods: Data from two previously conducted double-blind, prospective, phase 3 studies (NCT01982240, NCT02122471) were pooled. Patients were randomized to placebo (PBO; n=885) or plecanatide 3 mg (PLE; n=877) for 12 weeks. Electronic diaries recorded daily abdominal symptoms using a 5-point Likert scale (0=none; 4=very severe) and daily bowel movements. Responder outcomes were evaluated using an electronic diary and measured weekly: bowel movements (≥3 complete spontaneous bowel movements per week [CSBMs/week]); abdominal pain response (≥30% reduction from baseline in abdominal pain scores); and bloating response (≥30% reduction from baseline in abdominal bloating). The time to achieve the first weekly response was defined by the number of study weeks until a patient achieved their first week of response using a Cox proportional hazards model. Durability of response was defined as the percentage of study weeks in which patients achieved a weekly response.
Results: Plecanatide-treated patients experienced a significantly shorter median time to achieve the first weekly response in bowel symptom response (PLE, 3 weeks to achieve clinical response; PBO, 10 weeks to achieve clinical response [P< 0.001]); abdominal pain response (PLE, 3 weeks; PBO, 5 weeks [P< 0.01]); and, bloating response (PLE, 4 weeks; PBO, 5 weeks [P< 0.001]) (Figure 1). Regarding durability of response, a higher percentage of plecanatide patients reported bowel symptom response for at least ≥9 of the total 12 study weeks (PLE, 26%; PBO, 14% [P< 0.001]). Similarly, the durability of pain response (PLE, 37%, PBO, 29% [P< 0.001]) and bloating response (PLE, 33%; PBO, 25% [P< 0.001]) was greater with plecanatide compared to placebo. Overall, plecanatide was safe and efficacious for treating patients with CIC.
Discussion: Across 12 weeks of treatment in two CIC phase III trials, plecanatide 3 mg demonstrated a shorter time to achieve the first weekly response and greater durability of response compared to placebo with consistent findings across patient-reported outcome measures of constipation, abdominal pain, and bloating.
Figure: Figure 1. Kaplan-Meier Curves of Time to First Response for (A) ≥3 CSBMs, (B) ≥30% Reduction From Baseline in Abdominal Pain, and (C) ≥30% Reduction from Baseline in Bloating.
Eric Shah indicated no relevant financial relationships.
Alfred Nelson indicated no relevant financial relationships.
Sarah Lorenzen: Salix Pharmaceuticals Inc. – Employee.
Brian Lacy indicated no relevant financial relationships.
Eric Shah, MD, MBA1, William D. Chey, MD, FACG2, Alfred Nelson, MD3, Sarah Lorenzen, PhD4, Brian E. Lacy, MD, PhD, FACG3. P1448 - Plecanatide Produces a More Rapid and Durable Clinical Response Compared to Placebo in Patients With Chronic Idiopathic Constipation: A Post-Hoc Analysis of Two Randomized Controlled Trials, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.