Category: Professional Posters
Purpose: Irritable bowel syndrome with constipation (IBS-C) is a chronic condition that significantly impacts quality of life. Plecanatide is structurally similar to human uroguanylin, an intestinal peptide that induces fluid and ion secretion, but contains a single amino acid substitution. Plecanatide is approved in the United States for the treatment of IBS-C in adult patients. The objective of this analysis is to evaluate the efficacy and safety of plecanatide in patients with IBS-C in two identically designed phase 3 trials, including the impact on patient-reported secondary outcomes.
Methods: Data were pooled from two 12-week, randomized, double-blind, phase 3 clinical trials of plecanatide in adults with CIC (NCT02387359; NCT02493452). Patients (aged 18–85 yrs) meeting Rome III criteria for IBS-C were eligible to participate and were randomized to once-daily placebo, plecanatide 3 mg, or plecanatide 6 mg. The primary efficacy endpoint in both trials was the percentage of Overall Responders, defined as a patient who was both an Abdominal Pain Responder (≥30% decrease in worst abdominal pain vs baseline) and Stool Frequency Responder (increase ≥1 complete spontaneous bowel movement vs baseline) in the same week for ≥6 of 12 treatment weeks. Safety and tolerability were assessed by the incidence, nature, and severity of adverse events (AEs). Efficacy and safety data from these two 12-week trials were pooled.
Results: A total of 1456 patients were included in the combined intention-to-treat population (placebo, N=733; 3 mg, N=728; 6 mg, N=728). Demographics were similar between treatment groups and across the studies. Plecanatide treatment resulted in a significantly greater percentage of Overall Responders than did placebo (placebo, 16.0%; 3 mg, 25.7%; 6 mg, 26.6%; P < 0.001 both doses). A significantly greater percentage of plecanatide-treated patients were weekly Abdominal Pain Responders (placebo, 27.3%; 3 mg, 36.8%; 6 mg, 39.1%; P < 0.001 both doses) and weekly Stool Frequency Responders (placebo, 31.4%; 3 mg, 40.9%; 6 mg, 41.9%; P < 0.001 both doses) for ≥6 weeks of the 12-week studies. Plecanatide significantly improved patient-reported symptoms including stool consistency and straining severity. AE rates were similar in all 3 groups, with the only AE occurring in ≥2% of patients and with an incidence greater than placebo being diarrhea (placebo, 1.0%; 3 mg, 4.3%; 6 mg, 4.0%). There were low rates of discontinuation due to diarrhea (placebo, 0%; 3 mg, 1.2%; 6 mg, 1.4%).
Conclusion: Results for this pooled analysis indicate that plecanatide is efficacious and safe in patients with IBS-C. The hallmark symptoms of IBS-C, abdominal pain and reduced stool frequency, as well as secondary symptoms, were significantly improved with 12 weeks of once-daily plecanatide treatment compared with placebo. In plecanatide-treated patients, there were low AE and discontinuation rates, including diarrhea.