Category: Professional Posters
Purpose: Patients with chronic idiopathic constipation (CIC) suffer from infrequent or difficult stool passage and often report accompanying abdominal symptoms, such as bloating and discomfort. 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 CIC in adult patients. The objective of this analysis is to evaluate the efficacy and safety of plecanatide in patients with CIC 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 (NCT01982240; NCT02122471). Patients (aged 18–85 years) meeting modified Rome III criteria for CIC were eligible to participate and were randomized (1:1:1) to plecanatide 3mg, plecanatide 6mg, or placebo for 12 weeks. The primary efficacy endpoint was the percentage of durable overall complete spontaneous bowel movement (CSBM) responders. Secondary efficacy endpoints included the mean change from baseline (∆) in the frequency of CSBMs and spontaneous bowel movements (SBMs), as well as the assessment of patient-reported symptoms of straining, abdominal bloating, and abdominal discomfort. Efficacy and safety data from these two 12-week trials were pooled.
Results: The combined efficacy population included 2683 patients (3mg, N=896; 6mg, N=890; placebo, N=897). Significantly more patients treated with plecanatide were durable overall CSBM responders over 12 weeks of treatment (3mg, 20.5%; 6mg, 19.8%; placebo, 11.5%; P < 0.001 vs placebo both doses). A significantly greater change in CSBM frequency was demonstrated for plecanatide (3mg, ∆=1.07; 6mg, 0.89; P < 0.001 vs placebo both doses), as well as in SBM frequency (3mg, ∆=1.51; 6mg, 1.58; P < 0.001 vs placebo both doses). Significant reductions in patient-reported outcomes were observed favoring plecanatide vs placebo, including for straining (3mg, ∆=−0.31; 6mg, ∆=−0.27; P < 0.001 vs placebo both doses), and the perceptive symptoms of abdominal bloating (3mg, ∆=−0.12; P < 0.001 vs placebo; 6mg, ∆=−0.08; P=0.009 vs placebo), and discomfort (3mg, ∆=−0.11; P < 0.001 vs placebo; 6mg, ∆=−0.07; P=0.027 vs placebo). Both plecanatide doses were safe and well tolerated. The most common adverse event (AE) was diarrhea (3mg, 4.6%; 6mg, 5.1%; placebo, 1.3%). Discontinuation rates due to AEs were 4.1% (3mg), 4.5% (6mg), and 2.2% (placebo), with low discontinuation due to diarrhea (3mg, 1.9%; 6mg, 1.8%; placebo, 0.4%).
Conclusion: Results for this pooled analysis indicate that plecanatide is efficacious, safe, and well-tolerated in patients with CIC. Compared with placebo, plecanatide 3mg and 6mg demonstrated durable improvements in key clinical outcomes for patients with CIC, including improvements in stool frequency, straining, and perceptive abdominal symptoms.