Randomized, Double-blind, Dose-range-finding, Phase 2 Study of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Irritable Bowel Syndrome With Constipation Clinical Trial

Official title:

A Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-design, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Irritable Bowel Syndrome With Constipation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00460811
• Other study ID #: MCP-103-202
• Status: Completed
• Phase: Phase 2
• First received: April 13, 2007
• Last updated: January 29, 2013
• Start date: April 2007
• Est. completion date: April 2008

Study information

• Verified date: January 2013
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety, efficacy, and dose response of a range of oral doses of linaclotide administered to patients meeting criteria for IBS-C.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: April 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must not be pregnant or breastfeeding and agree to use birth control;

• Completion of a negative colonoscopy as per American Gastroenterology Association (AGA) criteria and no clinically-significant laboratory or physical examination findings;

• Meets protocol-defined criteria for IBS-C, including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria;

• Demonstrates English fluency and has access to a touch-tone telephone.

Exclusion Criteria:

• Recent history of mushy or watery stools;

• Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study;

• Clinically-significant alarm symptoms;

• Secondary causes of constipation or evacuation disorders;

• Surgery to the gastrointestinal tract;

• Usage of prohibited medications.

Study Design

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

Related Conditions & MeSH terms

• Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Constipation
• Syndrome

Intervention

Drug:
• Linaclotide Acetate
Oral, once daily
• Matching placebo
Oral, once daily

Locations

Country	Name	City	State
Canada	Microbia Investigational Site	Abbortsford	British Columbia
Canada	Microbia Investigational Site	Guelph	Ontario
Canada	Microbia Investigational Site	Milton	Ontario
Canada	Microbia Investigational Site	Saskatoon	Saskatchewan
Canada	Microbia Investigational Site	Toronto	Ontario
Canada	Microbia Investigational Site	Winnipeg	Manitoba
United States	Microbia Investigational Site	Anaheim	California
United States	Microbia Investigational Site	Anderson	South Carolina
United States	Microbia Investigational Site	Ann Arbor	Michigan
United States	Microbia Investigational Site	Annapolis	Maryland
United States	Microbia Investigational Site	Asheville	North Carolina
United States	Microbia Investigational Site	Baton Rouge	Louisiana
United States	Microbia Investigational Site	Beaumont	Texas
United States	Microbia Investigational Site	Blackwood	New Jersey
United States	Microbia Investigational Site	Boynton Beach	Florida
United States	Microbia Investigational Site	Bristol	Connecticut
United States	Microbia Investigational Site	Bristol	Tennessee
United States	Microbia Investigational Site	Chandler	Arizona
United States	Microbia Investigational Site	Chapel Hill	North Carolina
United States	Microbia Investigational Site	Charleston	West Virginia
United States	Microbia Investigational Site	Chesapeake	Virginia
United States	Microbia Investigational Site	Cincinnati	Ohio
United States	Microbia Investigational Site	Cleveland	Ohio
United States	Microbia Investigational Site	Clive	Iowa
United States	Microbia Investigational Site	Corsicana	Texas
United States	Microbia Investigational Site	Davenport	Iowa
United States	Microbia Investigational Site	Dayton	Ohio
United States	Microbia Investigational Site	Dunedin	Florida
United States	Microbia Investigational Site	El Paso	Texas
United States	Microbia Investigational Site	Elkin	North Carolina
United States	Microbia Investigational Site	Fall River	Massachusetts
United States	Microbia Investigational Site	Garden Grove	California
United States	Microbia Investigational Site	Germantown	Tennessee
United States	Microbia Investigational Site	Great Neck	New York
United States	Microbia Investigational Site	Greensboro	North Carolina
United States	Microbia Investigational Site	Harrisburg	North Carolina
United States	Microbia Investigational Site	Henderson	Nevada
United States	Microbia Investigational Site	Hickory	North Carolina
United States	Microbia Investigational Site	Huntsville	Alabama
United States	Microbia Investigational Site	Jackson	Tennessee
United States	Microbia Investigational Site	Kingsport	Tennessee
United States	Microbia Investigational Site	LaCrosse	Wisconsin
United States	Microbia Investigational Site	Lakewood	Washington
United States	Microbia Investigational Site	Largo	Florida
United States	Microbia Investigational Site	Las Vegas	Nevada
United States	Microbia Investigational Site	Levittown	Pennsylvania
United States	Microbia Investigational Site	Libertyville	Illinois
United States	Microbia Investigational Site	Lynchburg	Virginia
United States	Microbia Investigational Site	Medford	Oregon
United States	Microbia Investigational Site	Mission	Kansas
United States	Microbia Investigational Site	Missoula	Montana
United States	Microbia Investigational Site	Monroe	Louisiana
United States	Microbia Investigational Site	Mt. Pleasant	South Carolina
United States	Microbia Investigational Site	Ocala	Florida
United States	Microbia Investigational Site	Ogden	Utah
United States	Microbia Investigational Site	Oklahoma City	Oklahoma
United States	Microbia Investigational Site	Olympia	Washington
United States	Microbia Investigational Site	Peoria	Illinois
United States	Microbia Investigational Site	Pittsburgh	Pennsylvania
United States	Microbia Investigational Site	Pittsford	New York
United States	Microbia Investigational Site	Port Orange	Florida
United States	Microbia Investigational Site	Raleigh	North Carolina
United States	Microbia Investigational Site	Reading	Pennsylvania
United States	Microbia Investigational Site	Richmond	Virginia
United States	Microbia Investigational Site	Sacramento	California
United States	Microbia Investigational Site	San Antonio	Texas
United States	Microbia Investigational Site	San Diego	California
United States	Microbia Investigational Site	Sellersville	Pennsylvania
United States	Microbia Investigational Site	Shawnee	Kansas
United States	Microbia Investigational Site	Sherwood	Arkansas
United States	Microbia Investigational Site	Silver Spring	Maryland
United States	Microbia Investigational Site	Simpsonville	South Carolina
United States	Microbia Investigational Site	St. Louis	Missouri
United States	Microbia Investigational Site	Statesville	North Carolina
United States	Microbia Investigational Site	Stockbridge	Georgia
United States	Microbia Investigational Site	Stuart	Florida
United States	Microbia Investigational Site	Summerville	South Carolina
United States	Microbia Investigational Site	Sylvania	Ohio
United States	Microbia Investigational Site	Tampa	Florida
United States	Microbia Investigational Site	Tulsa	Oklahoma
United States	Microbia Investigational Site	Tuscon	Arizona
United States	Microbia Investigational Site	Vancouver	Washington
United States	Microbia Investigational Site	West Monroe	Louisiana
United States	Microbia Investigational Site	Winston-Salem	North Carolina
United States	Microbia Investigational Site	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Weekly Normalized Complete Spontaneous Bowel Movement (CSBM) Rate During Weeks 1 Through 12 of the Treatment Period	The change in the weekly normalized CSBM Rate during Weeks 1 through 12 of the Treatment Period from the weekly normalized CSBM Rate obtained during the Pretreatment Period.; The CSBM rate was normalized based on the number of CSBMs occurring in that week, adjusting for differences in the duration of the week and black-out periods (time not covered due to a missed IVRS call) versus 7x24 hours.	Change from Baseline to Week 12	No
Secondary	CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate)	For each week of the Treatment and Posttreatment Periods, a patient was considered a CSBM Responder if for that week the patient 1) completed = 4 days of IVRS questions, 2) had a CSBM rate of = 3 for the week, and 3) had an increase in CSBM rate of = 1 from the baseline weekly CSBM rate.	Change from Baseline to Week 12	No
Secondary	Change From Baseline in the Weekly Normalized SBM Rate for the Treatment Period	SBMs were measured daily during the treatment period by patient calls to the IVRS.	Change from Baseline to Week 12	No
Secondary	Change From Baseline in Stool Consistency (7-point Ordinal BSFS) for the Treatment Period	Stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 1 = separate hard lumps like nuts (difficult to pass); 2 = sausage shaped but lumpy; 3 = like a sausage but with cracks on surface; 4 = like a sausage or snake, smooth and soft; 5 = soft blobs with clear-cut edges (passed easily); 6 = fluffy pieces with ragged edges, a mushy stool; and 7 = watery, no solid pieces (entirely liquid).	Change from Baseline to Week 12	No
Secondary	Change From Baseline in Straining (5-point Ordinal Scale) for the Treatment Period	Straining was assessed using a 5-point ordinal scale, whereby a score of 1 = not at all, 2 = a little bit, 3 = a moderate amount, 4 = a great deal, and 5 = an extreme amount.	Change from Baseline to Week 12	No
Secondary	Change From Baseline in Degree of Relief of Irritable Bowel Syndrome (IBS) Symptoms (7-point Balanced Scale) for the Treatment Period	Patients provided a weekly assessment of Degree of Relief of IBS Symptoms using a 7-point balanced scale (1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse, 7=as bad as I can imagine).	Change from Baseline to Week 12	No
Secondary	Change From Baseline in Abdominal Pain (5-point Ordinal Scale) for the Treatment Period	During the study, patients provided their self assessment of abdominal pain using a 5-point ordinal scale (1=none, 2=mild, 3=moderate, 4=severe, 5=very severe	Change from Baseline to Week 12	No