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

Phase 2
Completed
Conditions
Irritable Bowel Syndrome With Constipation
Interventions
Drug: Matching placebo
Registration Number
NCT00460811
Lead Sponsor
Ironwood Pharmaceuticals, Inc.
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
420
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
72 ug linaclotide acetateLinaclotide Acetate-
145 ug linaclotide acetateLinaclotide Acetate-
290 ug linaclotide acetateLinaclotide Acetate-
579 ug linaclotide acetateLinaclotide Acetate-
Matching PlaceboMatching placebo-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in the Weekly Normalized Complete Spontaneous Bowel Movement (CSBM) Rate During Weeks 1 Through 12 of the Treatment PeriodChange from Baseline to Week 12

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.

Secondary Outcome Measures
NameTimeMethod
CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate)Change from Baseline to Week 12

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 in the Weekly Normalized SBM Rate for the Treatment PeriodChange from Baseline to Week 12

SBMs were measured daily during the treatment period by patient calls to the IVRS.

Change From Baseline in Stool Consistency (7-point Ordinal BSFS) for the Treatment PeriodChange from Baseline to Week 12

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 in Straining (5-point Ordinal Scale) for the Treatment PeriodChange from Baseline to Week 12

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 in Degree of Relief of Irritable Bowel Syndrome (IBS) Symptoms (7-point Balanced Scale) for the Treatment PeriodChange from Baseline to Week 12

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 in Abdominal Pain (5-point Ordinal Scale) for the Treatment PeriodChange from Baseline to Week 12

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

Trial Locations

Locations (1)

Microbia Investigational Site

🇨🇦

Saskatoon, Saskatchewan, Canada

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