A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation

Am J Gastroenterol. 2017 Apr;112(4):613-621. doi: 10.1038/ajg.2016.611. Epub 2017 Feb 7.


Objectives: This study assessed the efficacy and safety of plecanatide, a guanylate cyclase-C (GC-C) agonist and the first uroguanylin analog approved for the treatment of chronic idiopathic constipation (CIC).

Methods: This phase III, multicenter, double-blind, placebo-controlled study randomized 1,394 patients with CIC. Patients received either plecanatide (3 or 6 mg) or placebo, orally, once daily, for 12 weeks. The primary efficacy endpoint was the percentage of patients who were durable overall complete spontaneous bowel movement (CSBM) responders over the 12-week treatment period. Patients were instructed to record their daily bowel movements, stool consistency scores, and abdominal symptoms in an electronic diary. Treatment-emergent adverse events (AEs) were collected.

Results: Each dose of plecanatide resulted in a significantly greater percentage of durable overall CSBM responders (21.0%, 3 mg; 19.5%, 6 mg) as compared with placebo (10.2%; P<0.001 for both). Plecanatide (3 and 6 mg) also significantly increased mean weekly CSBM frequency from baseline (increase of 2.5 and 2.2/week, respectively) vs. placebo (1.2/week; P<0.001 for both) and mean weekly spontaneous bowel movement frequency (increase of 3.2 and 3.1/week, respectively) vs. placebo (1.3/week; P<0.001, for both) over the 12-week treatment period. Both plecanatide doses significantly improved all secondary and additional efficacy endpoints. The most common AE, diarrhea, occurred in 1.3% (placebo), 5.9% (3 mg) and 5.7% (6 mg) of patients.

Conclusions: Plecanatide significantly improved constipation and its related symptoms with a low rate of adverse events. These results suggest that plecanatide will be a useful treatment option in the management of CIC. ClinicalTrials.gov: NCT01982240.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chronic Disease
  • Constipation / drug therapy*
  • Defecation
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptides / therapeutic use*
  • Treatment Outcome
  • Young Adult


  • Gastrointestinal Agents
  • Natriuretic Peptides
  • plecanatide

Associated data

  • ClinicalTrials.gov/NCT01982240