Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating

Chronic Constipation Clinical Trial

Official title:

Phase 3b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Chronic Constipation and Prominent Abdominal Bloating at Baseline

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01642914
• Other study ID #: LIN-MD-04
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2012
• Last updated: September 30, 2013
• Start date: August 2012
• Est. completion date: August 2013

Study information

• Verified date: September 2013
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of linaclotide compared with placebo in patients with chronic constipation (CC) and prominent abdominal bloating. This study includes an up to 3-week screening period and a 2-3 week pretreatment period. Patients who are eligible will be randomized to one of two doses of linaclotide or placebo for 12 weeks. This 12-week study will assess the effects of linaclotide on bowel movement frequency, as well as other abdominal and bowel symptoms of CC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 487
• Est. completion date: August 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient has completed a colonoscopy according to the American Gastroenterological Association criteria with no clinically significant findings

• Patient has successfully completed protocol procedures (with no clinically significant findings)

• Patient meets protocol criteria for Chronic Constipation(CC): < 3 bowel movements per week and reports one or more of the following symptoms for at least 12 weeks:

1. Straining during more than 25% of BMs

2. Lumpy or hard stools during more than 25% of BMs

3. Sensation of incomplete evacuation during more than 25% of BMs

• Patient demonstrates continued chronic constipation and bloating through Pretreatment Period

• Patient is compliant with Interactive voice response System (IVRS)

Exclusion Criteria:

• Patient has a 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 would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Constipation
• Constipation

Intervention

Drug:
• Linaclotide 290 micrograms
oral capsule, taken once daily each morning at least 30 minutes before breakfast
• Linaclotide 145 micrograms
oral capsule, taken once daily each morning at least 30 minutes before breakfast
• Matching placebo
oral capsule, taken once daily each morning at least 30 minutes before breakfast

Locations

Country	Name	City	State
Canada	Forest Investigative Site 059	Sarnia	Ontario
Canada	Forest Investigative Site 054	Sudbury	Ontario
Canada	Forest Investigative Site 086	Toronto	Ontario
Canada	Forest Investigative Site 147	Toronto	Ontario
Canada	Forest Investigative Site 152	Vaughan	Ontario
United States	Forest Investigative Site 063	Albuquerque	New Mexico
United States	Forest Investigative Site 093	Albuquerque	New Mexico
United States	Forest Investigative Site 106	Anaheim	California
United States	Forest Investigative Site 107	Anderson	Indiana
United States	Forest Investigative Site 142	Asheboro	North Carolina
United States	Forest Investigative Site 094	Asheville	North Carolina
United States	Forest Investigative Site 125	Austin	Texas
United States	Forest Investigative Site 062	Baltimore	Maryland
United States	Forest Investigative Site 121	Baton Rouge	Louisiana
United States	Forest Investigative Site 075	Boone	North Carolina
United States	Forest Investigative Site 006	Boston	Massachusetts
United States	Forest Investigative Site 012	Boulder	Colorado
United States	Forest Investigative Site 091	Boynton Beach	Florida
United States	Forest Investigative Site 047	Bradenton	Florida
United States	Forest Investigative Site 007	Bristol	Connecticut
United States	Forest Investigative Site 044	Brooklyn	New York
United States	Forest Investigative Site 042	Brooksville	Florida
United States	Forest Investigative Site 020	Chandler	Arizona
United States	Forest Investigative Site 102	Chandler	Arizona
United States	Forest Investigative Site 123	Chapel Hill	North Carolina
United States	Forest Investigative Site 053	Charlottesville	Virginia
United States	Forest Investigative Site 129	Chattanooga	Tennessee
United States	Forest Investigative Site 108	Chesapeake	Virginia
United States	Forest Investigative Site 136	Chesapeake	Virginia
United States	Forest Investigative Site 070	Chesterfield	Michigan
United States	Forest Investigative Site 008	Chevy Chase	Maryland
United States	Forest Investigative Site 148	Christiansburg	Virginia
United States	Forest Investigative Site 025	Cincinnati	Ohio
United States	Forest Investigative Site 120	Cincinnati	Ohio
United States	Forest Investigative Site 056	Cleveland	Ohio
United States	Forest Investigative Site 036	Clifton	New Jersey
United States	Forest Investigative Site 117	Clive	Iowa
United States	Forest Investigative Site 146	Clive	Iowa
United States	Forest Investigative Site 041	Colorado Springs	Colorado
United States	Forest Investigative Site 045	Colorado Springs	Colorado
United States	Forest Investigative Site 026	Columbus	Ohio
United States	Forest Investigative Site 133	Coral Gables	Florida
United States	Forest Investigative Site 092	Dakota Dunes	South Dakota
United States	Forest Investigative Site 005	Dallas	Texas
United States	Forest Investigative Site 035	Dallas	Texas
United States	Forest Investigative Site 143	Davenport	Iowa
United States	Forest Investigative Site 140	Davidson	North Carolina
United States	Forest Investigative Site 090	Dayton	Ohio
United States	Forest Investigative Site 098	Dayton	Ohio
United States	Forest Investigative Site 131	DeLand	Florida
United States	Forest Investigative Site 039	Fayetteville	North Carolina
United States	Forest Investigative Site 111	Fort Worth	Texas
United States	Forest Investigative Site 077	Fremont	Nebraska
United States	Forest Investigative Site 051	Ft. Myers	Florida
United States	Forest Investigative Site 149	Glendale	Arizona
United States	Forest Investigative Site 126	Goodyear	Arizona
United States	Forest Investigative Site 017	Great Neck	New York
United States	Forest Investigative Site 029	Greensboro	North Carolina
United States	Forest Investigative Site 031	Greensboro	North Carolina
United States	Forest Investigative Site 078	Greensboro	North Carolina
United States	Forest Investigative Site 116	Greer	South Carolina
United States	Forest Investigative Site 014	Hagerstown	Maryland
United States	Forest Investigative Site 084	Harrisburg	North Carolina
United States	Forest Investigative Site 052	Henderson	Nevada
United States	Forest Investigative Site 050	Hickory	North Carolina
United States	Forest Investigative Site 073	Hickory	North Carolina
United States	Forest Investigative Site 139	High Point	North Carolina
United States	Forest Investigative Site 100	Houston	Texas
United States	Forest Investigative Site 015	Idaho Falls	Idaho
United States	Forest Investigative Site 137	Inverness	Florida
United States	Forest Investigative Site 055	Iowa City	Iowa
United States	Forest Investigative Site 141	Jackson	Mississippi
United States	Forest Investigative Site 114	Jacksonville	Florida
United States	Forest Investigative Site 004	Jupiter	Florida
United States	Forest Investigative Site 067	Katy	Texas
United States	Forest Investigative Site 138	Kingsport	Tennessee
United States	Forest Investigative Site 016	Kissimmee	Florida
United States	Forest Investigative Site 082	La Crosse	Wisconsin
United States	Forest Investigative Site 104	Laguna Hills	California
United States	Forest Investigative Site 080	Las Vegas	Nevada
United States	Forest Investigative Site 097	Lauderdale Lakes	Florida
United States	Forest Investigative Site 081	Levittown	Pennsylvania
United States	Forest Investigative Site 128	Lexington	Kentucky
United States	Forest Investigative Site 060	Longmont	Colorado
United States	Forest Investigative Site 072	Lynchburg	Virginia
United States	Forest Investigative Site 134	Madisonville	Kentucky
United States	Forest Investigative Site 011	Marietta	Georgia
United States	Forest Investigative Site 021	Marietta	Georgia
United States	Forest Investigative Site 088	Marlton	New Jersey
United States	Forest Investigative Site 085	Mentor	Ohio
United States	Forest Investigative Site 124	Metairie	Louisiana
United States	Forest Investigative Site 002	Miami	Florida
United States	Forest Investigative Site 003	Miami	Florida
United States	Forest Investigative Site 096	Milwaukee	Wisconsin
United States	Forest Investigative Site 066	Mission Hills	California
United States	Forest Investigative Site 101	Monroe	Louisiana
United States	Forest Investigative Site 130	New Smyrna Beach	Florida
United States	Forest Investigative Site 069	Newport News	Virginia
United States	Forest Investigative Site 028	Newton	Kansas
United States	Forest Investigative Site 013	Norfolk	Virginia
United States	Forest Investigative Site 135	North Little Rock	Arkansas
United States	Forest Investigative Site 040	Ocala	Florida
United States	Forest Investigative Site 019	Ogden	Utah
United States	Forest Investigative Site 118	Oklahoma City	Oklahoma
United States	Forest Investigative Site 048	Omaha	Nebraska
United States	Forest Investigative Site 083	Orlando	Florida
United States	Forest Investigative Site 112	Overland Park	Kansas
United States	Forest Investigative Site 150	Oviedo	Florida
United States	Forest Investigative Site 049	Pasadena	Texas
United States	Forest Investigative Site 122	Peoria	Illinois
United States	Forest Investigative Site 018	Phoenix	Arizona
United States	Forest Investigative Site 061	Phoenix	Arizona
United States	Forest Investigative Site 001	Pittsburgh	Pennsylvania
United States	Forest Investigative Site 132	Port Orange	Florida
United States	Forest Investigative Site 027	Raleigh	North Carolina
United States	Forest Investigative Site 110	Reading	Pennsylvania
United States	Forest Investigative Site 038	Richmond	Virginia
United States	Forest Investigative Site 043	Rockford	Illinois
United States	Forest Investigative Site 105	Salt Lake City	Utah
United States	Forest Investigative Site 030	San Antonio	Texas
United States	Forest Investigative Site 076	San Antonio	Texas
United States	Forest Investigative Site 095	San Carlos	California
United States	Forest Investigative Site 009	San Diego	California
United States	Forest Investigative Site 113	Sandy	Utah
United States	Forest Investigative Site 109	Sandy Springs	Georgia
United States	Forest Investigative Site 151	Santa Monica	California
United States	Forest Investigative Site 022	Scottsdale	Arizona
United States	Forest Investigative Site 127	Seminole	Florida
United States	Forest Investigative Site 058	Shreveport	Louisiana
United States	Forest Investigative Site 099	Shreveport	Louisiana
United States	Forest Investigative Site 046	Simpsonville	South Carolina
United States	Forest Investigative Site 103	Spokane	Washington
United States	Forest Investigative Site 087	St. Petersburg	Florida
United States	Forest Investigative Site 119	Statesville	North Carolina
United States	Forest Investigative Site 037	Stockbridge	Georgia
United States	Forest Investigative Site 065	Sugarland	Texas
United States	Forest Investigative Site 064	Tampa	Florida
United States	Forest Investigative Site 024	Towson	Maryland
United States	Forest Investigative Site 145	Traverse City	Michigan
United States	Forest Investigative Site 071	Tucson	Arizona
United States	Forest Investigative Site 079	Tucson	Arizona
United States	Forest Investigative Site 033	Vineland	New Jersey
United States	Forest Investigative Site 068	Wadsworth	Ohio
United States	Forest Investigative Site 153	Waterbury	Connecticut
United States	Forest Investigative Site 010	Westlake Village	California
United States	Forest Investigative Site 032	Wichita	Kansas
United States	Forest Investigative Site 034	Wichita	Kansas
United States	Forest Investigative Site 089	Wilmington	North Carolina
United States	Forest Investigative Site 074	Winston-Salem	North Carolina
United States	Forest Investigative Site 023	Woodstock	Georgia
United States	Forest Investigative Site 115	Zephyrhills	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder	A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.	12-week treatment period	No
Secondary	Change from baseline in Abdominal Bloating	Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS)	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS)	A patient's 12-week CSBM frequency rate will be the CSBM rate (CSBMs/week) calculated over the 12-weeks of the Treatment Period.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change from baseline Spontaneous Bowel Movement (SBM) Frequency Rate	A patient's 12-week SBM frequency rate will be the SBM rate (SBMs/week) calculated over the 12-weeks of the Treatment Period.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change from baseline in Stool Consistency	Bristol Stool Form Scale will be used by the patient to determine stool consistency	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change from baseline in Severity of Straining	Severity of straining will be measured using a five-point ordinal scale.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change from baseline in Constipation Severity	Constipation severity will be measured weekly using a five-point ordinal scale.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change from baseline in the Number of Days with a Spontaneous Bowel Movement ( SBM)	calculated as number of days with at least 1 Spontaneous Bowel Movement (SBM) during the Treatment Period divided by treatment duration of the patient multiplied by 7	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Percentage change from baseline in Abdominal Bloating	Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS)	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Spontaneous Bowel Movement (SBM) within 24 hours after the first dose of investigational product	A patient considered a responder if he/she has at least 1 Spontaneous Bowel Movement (SBM) within 24 hours after taking the first dose of investigational product	reported within 24 hours of patient's first dose of investigational product	No
Secondary	Complete Spontaneous Bowel Movement (CSBM) + 1 Responder	CSBM +1 Responder is a patient who has an increase in the 12 week CSBM Frequency Rate of 1 or more from baseline over the Treatment Period.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Abdominal Bloating 30% Responder	12-Week Abdominal Bloating 30% Responder is a patient who has an improvement in his/her 12-week abdominal bloating score of at least 30% compared to baseline.	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Change in baseline in Abdominal Discomfort	Abdominal Discomfort will be measured daily using an 11-point Numerical Rating Scale (NRS)	calculated daily over the 12 weeks of the patient's Treatment Period.	No
Secondary	Time to First Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product	Time to First SBM after First Dose of Investigational Product is defined as the number of hours elapsing from the time of the first dose of investigational product is taken to the occurrence of the first SBM	number of hours from the time of the first dose of investigational product	No