PMID- 28169285
OWN - NLM
STAT- MEDLINE
DCOM- 20170620
LR  - 20220408
IS  - 1572-0241 (Electronic)
IS  - 0002-9270 (Print)
IS  - 0002-9270 (Linking)
VI  - 112
IP  - 4
DP  - 2017 Apr
TI  - A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in 
      Patients With Chronic Idiopathic Constipation.
PG  - 613-621
LID - 10.1038/ajg.2016.611 [doi]
AB  - 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.
FAU - Miner, Philip B Jr
AU  - Miner PB Jr
AD  - Oklahoma Foundation for Digestive Research, Oklahoma City, Oklahoma, USA.
FAU - Koltun, William D
AU  - Koltun WD
AD  - Medical Center for Clinical Research, San Diego, California, USA.
FAU - Wiener, Gregory J
AU  - Wiener GJ
AD  - GW Research, Inc., Chula Vista, California, USA.
FAU - De La Portilla, Marianela
AU  - De La Portilla M
AD  - Genoma Research Group, Inc., Miami, Florida, USA.
FAU - Prieto, Blas
AU  - Prieto B
AD  - Advance Medical Research Service, Corp., Miami, Florida, USA.
FAU - Shailubhai, Kunwar
AU  - Shailubhai K
AD  - Synergy Pharmaceuticals Inc., New York, New York, USA.
FAU - Layton, Mary Beth
AU  - Layton MB
AD  - Synergy Pharmaceuticals Inc., New York, New York, USA.
FAU - Barrow, Laura
AU  - Barrow L
AD  - Synergy Pharmaceuticals Inc., New York, New York, USA.
FAU - Magnus, Leslie
AU  - Magnus L
AD  - Synergy Pharmaceuticals Inc., New York, New York, USA.
FAU - Griffin, Patrick H
AU  - Griffin PH
AD  - Synergy Pharmaceuticals Inc., New York, New York, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01982240
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170207
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Natriuretic Peptides)
RN  - 7IK8Z952OK (plecanatide)
SB  - IM
CIN - Am J Gastroenterol. 2017 Nov;112(11):1750-1751. PMID: 29109497
CIN - Am J Gastroenterol. 2017 Nov;112(11):1751. PMID: 29109504
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Chronic Disease
MH  - Constipation/*drug therapy
MH  - Defecation
MH  - Diarrhea/chemically induced
MH  - Double-Blind Method
MH  - Female
MH  - Gastrointestinal Agents/*therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptides/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC5415706
COIS- Guarantor of the article: Leslie Magnus, MD. Specific author contributions: Study 
      concept: Drs Miner and Shailubhai; study design: Drs Miner, Barrow, and Griffin; 
      data acquisition: Drs Miner, Koltun, Wiener, De La Portilla, and Prieto; data 
      analysis: Drs Miner, Barrow, and Griffin and Ms Layton; data interpretation, 
      drafting of the manuscript, critical revision of the manuscript for important 
      intellectual content, and final approval of the manuscript: all authors. 
      Financial support: Funding for this trial and manuscript support were provided by 
      Synergy Pharmaceuticals Inc. Synergy Pharmaceuticals Inc. also provided the 
      plecanatide and placebo used for the study. Potential competing interests: Drs 
      Shailubhai, Barrow, Magnus, and Griffin and Ms Layton are employees and 
      stockholders of Synergy Pharmaceuticals Inc. Drs Miner, Koltun, Wiener, De La 
      Portilla, and Prieto were study investigators paid for their participation in 
      this clinical trial. Dr Koltun has received funding for either advisory boards or 
      speaking from the following institutions: Synergy Pharmaceuticals, Symiomix 
      Theraputics, Ferring Pharmaceuticals, Enteris Pharmaceuticals, and Shionogi Inc. 
      Dr Miner has received funding for advisory board meetings. Transcript Profiling: 
      does not apply.
EDAT- 2017/02/09 06:00
MHDA- 2017/06/21 06:00
PMCR- 2017/05/04
CRDT- 2017/02/08 06:00
PHST- 2016/08/01 00:00 [received]
PHST- 2016/12/02 00:00 [accepted]
PHST- 2017/02/09 06:00 [pubmed]
PHST- 2017/06/21 06:00 [medline]
PHST- 2017/02/08 06:00 [entrez]
PHST- 2017/05/04 00:00 [pmc-release]
AID - ajg2016611 [pii]
AID - 10.1038/ajg.2016.611 [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2017 Apr;112(4):613-621. doi: 10.1038/ajg.2016.611. Epub 2017 
      Feb 7.