Clinical trial NCT02291679: Trial of Linaclotide in Patients With Chronic Idiopathic Constipation
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide (72 ug or 145 ug) Administered Orally for 12 Weeks to Patients With Chronic Idiopathic Constipation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Idiopathic Constipation
Lead sponsor: Ironwood Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2014-11-14
Enrollment: 1223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial was to determine the efficacy and safety of linaclotide 72 ug administered once daily to patients with chronic idiopathic constipation (CIC). The primary efficacy parameter is the percentage of participants in each dosing group that meet the protocol definition for complete spontaneous bowel movement (CSBM) Overall Responder.

Detailed description: The trial also included a 145 ug linaclotide treatment arm (an FDA-approved dose for CIC) as an established positive control to validate the study design.

Eligibility criteria: Inclusion Criteria:

* Patient has completed a colonoscopy if one is needed according to the American Gastroenterological Association (AGA) criteria, with no clinically significant findings
* Patient has no clinically significant findings on a physical examination and clinical laboratory tests
* Patient meets protocol criteria for CIC: reports \< 3 bowel movements (BMs) per week and reports one or more of the following during ≥ 25% of BMs: straining, lumpy or hard stools, sensation of incomplete evacuation during the 3 months before the diagnosis with the onset at least 6 months before the diagnosis
* Patient is compliant with daily interactive voice response system (IVRS) calls
* Patient reports an average of \< 3 complete spontaneous BMs (CSBMs) and ≤ 6 SBMs per week by the IVRS over the 14 calendar days before the Randomization Visit and the calendar day of Randomization.

Exclusion Criteria:

* Patient has history of loose or watery stools
* Patient has symptoms of or been diagnosed with irritable bowel syndrome (IBS)
* Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
* Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments
* Patient has Bristol Stool Form Scale score of 7 during Pretreatment period.

Primary outcomes:
measure: Percentage of 12-Week CSBM Overall Responders
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in 12-Week CSBM Frequency Rate
timeFrame: Baseline, Week 1 to Week 12
measure: Change From Baseline in 12-Week SBM Frequency Rate
timeFrame: Baseline, Week 1 to Week 12
measure: Change From Baseline in 12-Week Stool Consistency Score
timeFrame: Baseline, Week 1 to Week 12
measure: Change From Baseline in 12-Week Straining Score
timeFrame: Baseline, Week 1 to Week 12
measure: Percentage of 12-Week CSBM Overall Responders (>1 SBM/Week Subpopulation)
timeFrame: Week 12
measure: Percentage of Month 1 CSBM Responders
timeFrame: Month 1
measure: Percentage of Month 2 CSBM Responders
timeFrame: Month 2
measure: Percentage of Month 3 CSBM Responders
timeFrame: Month 3
measure: Change From Baseline in 12-Week Abdominal Bloating
timeFrame: Baseline, Week 1 to Week 12
measure: Change From Baseline in 12-Week Abdominal Discomfort
timeFrame: Baseline, Week 1 to Week 12
Other outcomes:
measure: Percentage of 12-Week CSBM Overall Sustained Responders
timeFrame: Week 12
Locations:
city: Huntsville
country: United States
facility: Ironwood Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: Tucson
country: United States
facility: Ironwood Investigational Site
state: Arizona
city: North Little Rock
country: United States
facility: Ironwood Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: Ironwood Investigational Site
state: California
city: Chula Vista
country: United States
facility: Ironwood Investigational Site
state: California
city: Garden Grove
country: United States
facility: Ironwood Investigational Site
state: California
city: La Mesa
country: United States
facility: Ironwood Investigational Site
state: California
city: North Hollywood
country: United States
facility: Ironwood Investigational Site
state: California
city: Orange
country: United States
facility: Ironwood Investigational Site
state: California
city: San Diego
country: United States
facility: Ironwood Investigational Site
state: California
city: Thousand Oaks
country: United States
facility: Ironwood Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Ironwood Investigational Site
state: Colorado
city: Bristol
country: United States
facility: Ironwood Investigational Site
state: Connecticut
city: Boynton Beach
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Coral Gables
country: United States
facility: Ironwood Investigational Site
state: Florida
city: DeLand
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Inverness
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Jupiter
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Kissimmee
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Orlando
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Port Orange County
country: United States
facility: Ironwood Investigational Site
state: Florida
city: South Miami
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Tampa
country: United States
facility: Ironwood Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Winter Park
country: United States
facility: Ironwood Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Ironwood Investigational Site
state: Georgia
city: Oakwood
country: United States
facility: Ironwood Investigational Site
state: Georgia
city: Sandy Springs
country: United States
facility: Ironwood Investigational Site
state: Georgia
city: Evansville
country: United States
facility: Ironwood Investigational Site
state: Indiana
city: Bastrop
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Metairie
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Shreveport
country: United States
facility: Ironwood Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Chevy Chase
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Hagerstown
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Hollywood
country: United States
facility: Ironwood Investigational Site
state: Maryland
city: Boston
country: United States
facility: Ironwood Investigational Site
state: Massachusetts
city: Wellesley
country: United States
facility: Ironwood Investigational Site
state: Massachusetts
city: Chesterfield
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Troy
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Wyoming
country: United States
facility: Ironwood Investigational Site
state: Michigan
city: Jackson
country: United States
facility: Ironwood Investigational Site
state: Mississippi
city: Saint Louis
country: United States
facility: Ironwood Investigational Site
state: Missouri
city: Bozeman
country: United States
facility: Ironwood Investigational Site
state: Montana
city: Las Vegas
country: United States
facility: Ironwood Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Ironwood Investigational Site
state: Nevada
city: Brooklyn
country: United States
facility: Ironwood Investigational Site
state: New York
city: Endwell
country: United States
facility: Ironwood Investigational Site
state: New York
city: Great Neck
country: United States
facility: Ironwood Investigational Site
state: New York
city: Charlotte
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: High Point
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Lenoir
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Ironwood Investigational Site
state: North Carolina
city: Fargo
country: United States
facility: Ironwood Investigational Site
state: North Dakota
city: Cincinnati
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Mentor
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Sylvania
country: United States
facility: Ironwood Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Ironwood Investigational Site
state: Oklahoma
city: Levittown
country: United States
facility: Ironwood Investigational Site
state: Pennsylvania
city: Anderson
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Greer
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Simpsonville
country: United States
facility: Ironwood Investigational Site
state: South Carolina
city: Dakota Dunes
country: United States
facility: Ironwood Investigational Site
state: South Dakota
city: Bristol
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: Ironwood Investigational Site
state: Tennessee
city: Beaumont
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Dallas
country: United States
facility: Ironwood Investigational Site
state: Texas
city: El Paso
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Houston
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Houston
country: United States
facility: Ironwood Investigational Site
state: Texas
city: Longview
country: United States
facility: Ironwood Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Ironwood Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Ironwood Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Ironwood Investigational Site
state: Texas
city: South Ogden
country: United States
facility: Ironwood Investigational Site
state: Utah
city: Christiansburg
country: United States
facility: Ironwood Investigational Site
state: Virginia
city: Lynchburg
country: United States
facility: Ironwood Investigational Site
state: Virginia
city: La Crosse
country: United States
facility: Ironwood Investigational Site
state: Wisconsin
Study officials:
affiliation: Ironwood Pharmaceuticals, Inc.
name: Bernard J Lavins, MD
role: STUDY_CHAIR
References: