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

October 1, 2008
December 19, 2012
September 2008
July 2009   (final data collection date for primary outcome measure)
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.

Complete Spontaneous Bowel Movement (CSBM) Overall Responder [ Time Frame: Treatment Period to determine Overall Responder ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00765882 on ClinicalTrials.gov Archive Site
  • 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".
Change from Baseline in 12-week CSBM Frequency [ Time Frame: Each week for the Treatment Period ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Phase III, Randomized, Double-Blind, Placebo-Controlled, Trial of Linaclotide Administered to Patients With Chronic Constipation
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks in Patients With Chronic Constipation

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

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Chronic Constipation
  • Drug: Linaclotide 290 micrograms
    Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
  • Drug: Linaclotide 145 micrograms
    Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
  • Drug: Placebo
    Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
  • Experimental: 1
    Linaclotide 290 micrograms
    Intervention: Drug: Linaclotide 290 micrograms
  • Experimental: 2
    Linaclotide 145 micrograms
    Intervention: Drug: Linaclotide 145 micrograms
  • Placebo Comparator: 3
    Matching placebo
    Intervention: Drug: Placebo
Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, Shao JZ, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Eng P, Fox SM, Johnston JM. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36. doi: 10.1056/NEJMoa1010863.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
633
August 2009
July 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00765882
LIN-MD-01
Not Provided
Forest Laboratories
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
Study Director: Paul F.C. Eng, PhD Forest Laboratories
Forest Laboratories
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP