Background: Many patients with chronic idiopathic constipation (CIC) remain unsatisfied with their treatment options. Plecanatide is a pH-sensitive uroguanylin analog that increases fluid and ion movement into the gastrointestinal lumen, softening stools and encouraging motility, while limiting the risk of diarrhea.
Aims: The objective of this phase 2 study is to evaluate the safety and efficacy of once-daily oral plecanatide in patients with CIC and identify the most effective dose.
Methods: A 12-week, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study was conducted in patients aged 18-75 years and diagnosed with CIC based on modified Rome III criteria (< 3 complete spontaneous bowel movements [CSBMs] per week and infrequent loose stools without the use of laxatives). Participants were randomized to placebo or plecanatide 0.3, 1.0, or 3.0 mg. The primary efficacy endpoint was the proportion of overall CSBM responders. Key secondary endpoints included time to first CSBM, change in CSBM and spontaneous bowel movement (SBM) frequency rates, patient-reported outcomes, safety, and tolerability.
Results: Of 951 randomized participants, 946 were included in the modified intent-to-treat population. Plecanatide 0.3 and 3.0 mg significantly increased overall CSBM responder rates compared with placebo (0.3 mg, P = 0.016; 3.0 mg, P = 0.009). Plecanatide was associated with decreased time to first CSBM, significant increases in CSBM and SBM frequency, and decreased patient-reported constipation severity compared with placebo. Diarrhea was the most frequently reported treatment-emergent adverse event.
Conclusions: Plecanatide is a well-tolerated treatment that relieved the symptoms of CIC with a relatively low incidence of diarrhea.
Keywords: Clinical trial; Constipation; Phase 2; Plecanatide.