Clinical—Alimentary TractEfficacy of Linaclotide for Patients With Chronic Constipation
Section snippets
Study Design
A randomized, double-blind, parallel-group, placebo-controlled, dose-range−finding study was conducted at 57 clinical centers in the United States between November 2006 (first signed informed consent) and December 2007 (last patient visit). The study was performed in accordance with the Declaration of Helsinki and US21 Code of Federal Regulations. Written informed consent was obtained from all patients prior to their participating in the study. Each participating center's Institutional Review
Participant Flow and Demographics
Of the 639 patients who signed consent, 120 were screen failures, 209 were pretreatment failures, and 310 patients were randomized to 1 of the 5 arms of the study. One patient randomized to 150 μg linaclotide withdrew prior to receiving the study medication (safety population, n = 309), 2 additional patients withdrew prior to any postdose evaluation of the primary efficacy assessment (Intent-to-Treat population, n = 307) and 32 additional patients discontinued while receiving study medication
Discussion
In this dose-range−finding study in patients with CC, linaclotide, a minimally absorbed GC-C receptor agonist, significantly improved bowel habits and abdominal symptoms associated with constipation. Linaclotide's effects on bowel habits were observed within 24 hours after the start of the medication and maintained throughout the 4 weeks of treatment, with no evidence of rebound constipation after discontinuation of the medication during the 14-day follow-up period. There was evidence of a
Acknowledgments
The authors thank the investigators for their participation in this study.
The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician not employed by the corporate entity.
References (27)
- et al.
Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features
Am J Gastroenterol
(1999) - et al.
An epidemiological survey of constipation in Canada: definitions, rates, demographics, and predictors of health care seeking
Am J Gastroenterol
(2001) - et al.
A gap in our understanding: chronic constipation and its comorbid conditions
Clin Gastroenterol Hepatol
(2009) - et al.
Treatment of chronic constipation: current pharmacologic approaches and future directions
Clin Gastroenterol Hepatol
(2009) Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics
Pharmacol Ther
(2004)- et al.
Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome
Gastroenterology
(2007) - et al.
Functional bowel disorders
Gastroenterology
(2006) - et al.
Colorectal cancer screening and surveillance: clinical guidelines and rationale—update based on new evidence
Gastroenterology
(2003) - et al.
Epidemiology of constipation in North America: a systematic review
Am J Gastroenterol
(2004) - et al.
Chronic constipation
N Engl J Med
(2003)
The burden of constipation on quality of life: results of a multinational survey
Aliment Pharmacol Ther
Chronic constipation: a survey of the patient perspective
Aliment Pharmacol Ther
Functional gastrointestinal disorders as a public health problem
Neurogastroenterol Motil
Cited by (199)
Patient-Reported Outcomes in Disorders of Gut–Brain Interaction
2024, GastroenterologyPediatric and adolescent GI motility disorders and management
2023, Handbook of Gastrointestinal Motility and Disorders of Gut-Brain Interactions, Second EditionGuanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain
2022, Trends in Pharmacological SciencesPharmacological Treatments for Constipation and Opioid-Induced Constipation
2022, Comprehensive PharmacologyA practical approach to the evaluation and management of gastrointestinal symptoms in patients with systemic sclerosis
2021, Best Practice and Research: Clinical RheumatologyEvaluation and Treatment of Constipation in the Geriatric Population
2021, Clinics in Geriatric Medicine
Conflicts of interest The authors disclose the following: Jeffrey Johnston, Caroline Kurtz, James MacDougall, Bernard Lavins, Donald Fitch, Brenda Jeglinski, and Mark Currie are employees of Ironwood Pharmaceuticals. Anthony Lembo is a consultant to Ironwood Pharmaceuticals.
Funding This study was funded by Ironwood Pharmaceuticals.