Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation
Background: Plecanatide, with the exception of a single amino acid replacement, is identical to human uroguanylin and is approved in the United States for adults with chronic idiopathic constipation (CIC). This double-blind, placebo-controlled, phase III study evaluated the efficacy and safety of pl...
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doaj-13d128ce35eb4e6f9b8dcd50d17424082020-11-25T03:39:18ZengSAGE PublishingTherapeutic Advances in Gastroenterology1756-283X1756-28482017-11-011010.1177/1756283X17734697Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipationMichael DeMiccoLaura BarrowBernadette HickeyKunwar ShailubhaiPatrick GriffinBackground: Plecanatide, with the exception of a single amino acid replacement, is identical to human uroguanylin and is approved in the United States for adults with chronic idiopathic constipation (CIC). This double-blind, placebo-controlled, phase III study evaluated the efficacy and safety of plecanatide versus placebo in CIC. Methods: Adults meeting modified Rome III CIC criteria were randomized to plecanatide 3 mg ( n = 443), 6 mg ( n = 449), or placebo ( n = 445). Patients recorded bowel movement (BM) characteristics [including spontaneous BMs (SBMs) and complete SBMs (CSBMs)] and rated CIC symptoms in daily electronic diaries. The primary endpoint was the percentage of durable overall CSBM responders (weekly responders for ⩾9 of 12 treatment weeks, including ⩾3 of the last 4 weeks). Weekly responders had ⩾3 CSBMs/week and an increase of ⩾1 CSBM from baseline for the same week. Results: A significantly greater percentage of durable overall CSBM responders resulted with each plecanatide dose compared with placebo (3 mg = 20.1%; 6 mg = 20.0%; placebo = 12.8%; p = 0.004 each dose). Over the 12 weeks, plecanatide significantly improved stool consistency and stool frequency. Significant increases in mean weekly SBMs and CSBMs began in week 1 and were maintained through week 12 in plecanatide-treated patients. Adverse events were mostly mild/moderate, with diarrhea being the most common (3 mg = 3.2%; 6 mg = 4.5%; placebo = 1.3%). Conclusions: Plecanatide resulted in a significantly greater percentage of durable overall CSBM responders and improved stool frequency and secondary endpoints. Plecanatide was well tolerated; the most common AE, diarrhea, occurred in a small number of patients. [ClinicalTrials.gov identifier: NCT02122471]https://doi.org/10.1177/1756283X17734697 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael DeMicco Laura Barrow Bernadette Hickey Kunwar Shailubhai Patrick Griffin |
spellingShingle |
Michael DeMicco Laura Barrow Bernadette Hickey Kunwar Shailubhai Patrick Griffin Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation Therapeutic Advances in Gastroenterology |
author_facet |
Michael DeMicco Laura Barrow Bernadette Hickey Kunwar Shailubhai Patrick Griffin |
author_sort |
Michael DeMicco |
title |
Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
title_short |
Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
title_full |
Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
title_fullStr |
Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
title_full_unstemmed |
Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
title_sort |
randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation |
publisher |
SAGE Publishing |
series |
Therapeutic Advances in Gastroenterology |
issn |
1756-283X 1756-2848 |
publishDate |
2017-11-01 |
description |
Background: Plecanatide, with the exception of a single amino acid replacement, is identical to human uroguanylin and is approved in the United States for adults with chronic idiopathic constipation (CIC). This double-blind, placebo-controlled, phase III study evaluated the efficacy and safety of plecanatide versus placebo in CIC. Methods: Adults meeting modified Rome III CIC criteria were randomized to plecanatide 3 mg ( n = 443), 6 mg ( n = 449), or placebo ( n = 445). Patients recorded bowel movement (BM) characteristics [including spontaneous BMs (SBMs) and complete SBMs (CSBMs)] and rated CIC symptoms in daily electronic diaries. The primary endpoint was the percentage of durable overall CSBM responders (weekly responders for ⩾9 of 12 treatment weeks, including ⩾3 of the last 4 weeks). Weekly responders had ⩾3 CSBMs/week and an increase of ⩾1 CSBM from baseline for the same week. Results: A significantly greater percentage of durable overall CSBM responders resulted with each plecanatide dose compared with placebo (3 mg = 20.1%; 6 mg = 20.0%; placebo = 12.8%; p = 0.004 each dose). Over the 12 weeks, plecanatide significantly improved stool consistency and stool frequency. Significant increases in mean weekly SBMs and CSBMs began in week 1 and were maintained through week 12 in plecanatide-treated patients. Adverse events were mostly mild/moderate, with diarrhea being the most common (3 mg = 3.2%; 6 mg = 4.5%; placebo = 1.3%). Conclusions: Plecanatide resulted in a significantly greater percentage of durable overall CSBM responders and improved stool frequency and secondary endpoints. Plecanatide was well tolerated; the most common AE, diarrhea, occurred in a small number of patients. [ClinicalTrials.gov identifier: NCT02122471] |
url |
https://doi.org/10.1177/1756283X17734697 |
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