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

Abstract

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.

• Authors: Philip B Miner Jr, William D Koltun, Gregory J Wiener, Marianela De La Portilla, Blas Prieto, Kunwar Shailubhai, Mary Beth Layton, Laura Barrow, Leslie Magnus, Patrick H Griffin
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 112 Issue 4 Pg. 613-621 (04 2017) ISSN: 1572-0241 [Electronic] United States
• PMID: 28169285 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Gastrointestinal Agents
• Natriuretic Peptides
• plecanatide

Topics

• 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