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

This study has been completed.
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00765882
First received: October 1, 2008
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
Chronic Constipation
Drug: Linaclotide 290 micrograms
Drug: Linaclotide 145 micrograms
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks in Patients With Chronic Constipation

Resource links provided by NLM:


Further study details as provided by Forest Laboratories:

Primary Outcome Measures:
  • Complete Spontaneous Bowel Movement (CSBM) Overall Responder [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    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:
  • 12-week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    The number of CSBMs per week.

  • 12-Week Spontaneous Bowel Movement (SBM) Frequency Rate [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Bloating was based on a 5-point scale where a value of l is "none" and a value of 5 is "very severe".

  • 12-Week Constipation Severity [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    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".


Enrollment: 633
Study Start Date: September 2008
Study Completion Date: August 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Linaclotide 290 micrograms
Drug: Linaclotide 290 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
Experimental: 2
Linaclotide 145 micrograms
Drug: Linaclotide 145 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
Placebo Comparator: 3
Matching placebo
Drug: Placebo
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00765882

  Show 108 Study Locations
Sponsors and Collaborators
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
Investigators
Study Director: Paul F.C. Eng, PhD Forest Laboratories
  More Information

No publications provided by Forest Laboratories

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT00765882     History of Changes
Other Study ID Numbers: LIN-MD-01
Study First Received: October 1, 2008
Results First Received: September 28, 2012
Last Updated: December 19, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Forest Laboratories:
Constipation
Chronic Constipation
Linaclotide

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on September 22, 2014