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



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.



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.



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.
Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, USA.
Philip B
PB
Miner
Medical Center for Clinical Research, San Diego, California, USA.
William D
WD
Koltun
GW Research, Inc., Chula Vista, California, USA.
Gregory J
GJ
Wiener
Genoma Research Group, Inc., Miami, Florida, USA.
Marianela
M
De La Portilla
Advance Medical Research Service, Corp., Miami, Florida, USA.
Blas
B
Prieto
Synergy Pharmaceuticals Inc., New York, New York, USA.
Kunwar
K
Shailubhai
Synergy Pharmaceuticals Inc., New York, New York, USA.
Mary Beth
MB
Layton
Synergy Pharmaceuticals Inc., New York, New York, USA.
Laura
L
Barrow
Synergy Pharmaceuticals Inc., New York, New York, USA.
Leslie
L
Magnus
Synergy Pharmaceuticals Inc., New York, New York, USA.
Patrick H
PH
Griffin
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy*; D003672:Defecation; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D005765:Gastrointestinal Agents; D045265:Natriuretic Peptides; C584575:plecanatide