Dataset Information

Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial.

ABSTRACT: Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating.This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 ?g) or placebo once daily for 12 weeks. Eligible patients met Rome II criteria for chronic constipation upon entry with an average abdominal bloating score ?5 (self-assessment: 0 10-point numerical rating scale) during the 14-day baseline period. Patients reported abdominal symptoms (including bloating) and bowel symptoms daily; adverse events were monitored. The primary responder endpoint required patients to have ?3 complete spontaneous bowel movements/week with an increase of ?1 from baseline, for ?9 of 12 weeks. The primary endpoint compared linaclotide 145 ?g vs. placebo.The intent-to-treat population included 483 patients (mean age=47.3 years, female=91.5%, white=67.7%). The primary endpoint was met by 15.7% of linaclotide 145 ?g patients vs. 7.6% of placebo patients (P<0.05). Both linaclotide doses significantly improved abdominal bloating vs. placebo (P<0.05 for all secondary endpoints, controlling for multiplicity). Approximately one-third of linaclotide patients (each group) had ?50% mean decrease from baseline in abdominal bloating vs. 18% of placebo patients (P<0.01). Diarrhea was reported in 6% and 17% of linaclotide 145 and 290 ?g patients, respectively, and 2% of placebo patients. AEs resulted in premature discontinuation of 5% and 9% of linaclotide 145 ?g and 290 ?g patients, respectively, and 6% of placebo patients.Once-daily linaclotide (145 and 290 ?g) significantly improved bowel and abdominal symptoms in chronic idiopathic constipation patients with moderate-to-severe baseline abdominal bloating; in particular, linaclotide significantly improved abdominal bloating compared to placebo, an important finding given the lack of agents available to treat abdominal bloating in chronic idiopathic constipation patients.ClinicalTrials.gov NCT01642914.

SUBMITTER: Lacy BE

PROVIDER: S-EPMC4519259 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial.

Lacy Brian E BE Schey Ron R Shiff Steven J SJ Lavins Bernard J BJ Fox Susan M SM Jia Xinwei D XD Blakesley Rick E RE Hao Xinming X Cronin Jacquelyn A JA Currie Mark G MG Kurtz Caroline B CB Johnston Jeffrey M JM Lembo Anthony J AJ

PloS one 20150729 7

<h4>Background</h4>Abdominal bloating is a common and bothersome symptom of chronic idiopathic constipation. The objective of this trial was to evaluate the efficacy and safety of linaclotide in patients with chronic idiopathic constipation and concomitant moderate-to-severe abdominal bloating.<h4>Methods</h4>This Phase 3b, randomized, double-blind, placebo-controlled clinical trial randomized patients to oral linaclotide (145 or 290 μg) or placebo once daily for 12 weeks. Eligible patients met ...[more]

PMID: 26222318

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Project description:ObjectivesLinaclotide is a guanylate cyclase-C agonist approved in the United States, Canada, and Mexico at a once-daily 145-μg dose for the treatment of chronic idiopathic constipation (CIC); a once-daily 72-μg dose for CIC recently received FDA approval. The trial objective was to evaluate the efficacy and safety of a 72-μg linaclotide dose in CIC patients.MethodsThis double-blind, placebo-controlled trial randomized patients with CIC (Rome III criteria) to once-daily linaclotide 72 μg or 145 μg, or placebo for 12 weeks. The primary endpoint, 12-week complete spontaneous bowel movement (CSBM) overall responder, required patients to have ≥3 CSBMs and an increase of ≥1 CSBM per week from baseline in the same week for ≥9 of 12 weeks of the treatment period. Secondary endpoints included 12-week change from baseline in bowel (SBM and CSBM frequency, stool consistency, straining) and abdominal (bloating, discomfort) symptoms, monthly CSBM responders, and 12-week CSBM responders among patients who averaged >1 SBM/week at baseline. Sustained response (12-week CSBM overall responders who met weekly criteria for 3 of the 4 final weeks (weeks 9-12) of treatment) was evaluated as an additional endpoint. Adverse events (AEs) were monitored.ResultsThe intent-to-treat population included 1,223 patients (mean age=46 years, female=77%, white=71%). The primary endpoint was met by 13.4% of linaclotide 72-μg patients vs. 4.7% of placebo patients (P<0.0001, odds ratio=3.0; statistically significant controlling for multiplicity). Sustained response was achieved by 12.4% of linaclotide 72-μg patients vs. 4.2% of placebo patients (nominal P<0.0001). Linaclotide 72-μg patients met 9-of-10 secondary endpoints vs. placebo (P<0.05; abdominal discomfort, P=0.1028). Patients treated with linaclotide 145 μg also improved CIC symptoms for the primary (12.4%) and sustained responder endpoint parameters (11.4%) and for all 10 of the secondary endpoint parameters including abdominal discomfort (P<0.05). Diarrhea, the most common AE, was mild in most instances and resulted in discontinuation of 0, 2.4%, and 3.2% of patients in the placebo, linaclotide 72-μg, and linaclotide 145-μg groups, respectively.ConclusionsOnce-daily linaclotide 72 μg significantly improved CIC symptoms in both men and women with a low rate of discontinuation due to diarrhea over 12 weeks of treatment.

Dataset Information

Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial.

Publications

Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial.

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