Phase III, Randomized, Double-Blind, Placebo-Controlled, Trial of Linaclotide Administered to Patients With Chronic Constipation

Phase 3

Completed

• Conditions: Chronic Constipation
• Interventions: Drug: Linaclotide 290 micrograms; Drug: Linaclotide 145 micrograms; Drug: Placebo

• Registration Number: NCT00765882
• Lead Sponsor: Forest Laboratories

Brief Summary

The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with chronic constipation (CC). The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Complete Spontaneous Bowel Movement (CSBM) Overall Responder

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09
• Study First Submitted: 2008-10-01
• Study First Submitted QC: 2008-10-02
• Study First Posted: 2008-10-03
• Primary Completion: 2009-07
• Study Completion: 2009-08
• Disposition First Submitted: 2011-09-30
• Disposition First Submitted QC: 2011-09-30
• Disposition First Posted: 2011-10-05
• Results First Submitted: 2012-09-28
• Status Verified: 2012-12
• Results First Submitted QC: 2012-12-19
• Last Update Submitted: 2012-12-19
• Results First Posted: 2013-01-30
• Last Update Posted: 2013-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 633

Inclusion Criteria

• Patient has completed a colonoscopy according to the AGA criteria, with no clinically significant findings
• Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests
• Patient meets protocol criteria for CC: reports < 3 bowel movements per week and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during > 25% of BMs
• Patient demonstrates continued chronic constipation through Pretreatment Period
• Patient is compliant with IVRS

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Linaclotide 290 micrograms	Linaclotide 290 micrograms
2	Linaclotide 145 micrograms	Linaclotide 145 micrograms
3	Placebo	Matching placebo

Primary Outcome Measures

Name	Time	Method
Complete Spontaneous Bowel Movement (CSBM) Overall Responder	Change from Baseline to Week 12	A 12-week CSBM overall responders was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline.; A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation.; An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.

Secondary Outcome Measures

Name	Time	Method
12-Week Constipation Severity	Change from Baseline to Week 12	Constipation severity was based on a 5-point ordinal scale where a value of l is "none" and a value of 5 is "very severe".
12-week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate	Change from Baseline to Week 12	The number of CSBMs per week.
12-Week Spontaneous Bowel Movement (SBM) Frequency Rate	Change from Baseline to Week 12	A patient's 12-week spontaneous bowel movement (SBM) frequency rate was the number of SBMs per week calculated over the 12-weeks of the treatment period.
12-Week Stool Consistency	Change from Baseline to Week 12	The consistency of each BM was assessed using the 7-point Bristol Stool Form Scale: 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; 7. = watery, no solid pieces \[entirely liquid\]
12-Week Severity of Straining	Change from Baseline to Week 12	Straining is measured on a 5-point scale, where a value of 1 is "not at all" and a value of 5 is "an extreme amount.
12-Week Abdominal Discomfort	Change from Baseline to Week 12	Abdominal discomfort is based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe."
12-Week Bloating	Change from Baseline to Week 12	Bloating was based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe".

Trial Locations

Locations (4)

Forest Investigative Sites; 🇺🇸 Denver, Colorado, United States

Forest Investigative Site; 🇨🇦 Toronto, Ontario, Canada

Forest Investigative Site 1; 🇨🇦 Sarnia, Ontario, Canada

Forest Investigative Site 2; 🇨🇦 Sarnia, Ontario, Canada