Trial of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation

This study has been completed.
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00948818
First received: July 28, 2009
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 irritable bowel syndrome with constipation (IBS-C).

The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder.


Condition Intervention Phase
Irritable Bowel Syndrome Characterized by Constipation
Drug: Linaclotide 290 micrograms
Drug: Matching 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 Followed by a 4-Week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation

Resource links provided by NLM:


Further study details as provided by Forest Laboratories:

Primary Outcome Measures:
  • Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    A patient is considered to be an APC responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs, experienced an increase of at least 1 CSBM from baseline, and experienced a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week.

    The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP.

    A CSBM is defined as a spontaneous bowel movement, associated with a sense of complete evacuation.


  • Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    A patient is considered to be a CSBM 3+1 responder if, for at least 9 out of the 12 weeks of the treatment period, the patient had at least 3 CSBMs and experienced an increase of at least 1 CSBM from baseline during a particular week.

    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.


  • Abdominal Pain Responder, 9 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    A patient is considered to be an abdominal pain responder if, for at least 9 out of the 12 weeks of the treatment period, they experienced a decrease of at least 30 percent in the mean abdominal pain score from baseline during a particular week.

    The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.


  • Abdominal Pain and Complete Spontaneous Bowel Movement (APC) Responder, 6 Out of 12 Weeks. [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    A patient is considered an APC responder if, for at least 6 of the 12 weeks of the treatment, the patient experienced an increase of at least 1 Complete Spontaneous Bowel Movement (CSBM) from baseline and experienced a decrease of at least 30 percent in their Abdominal Pain (AP)score during a particular week.

    The AP score assesses the worst of a patient's AP in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no AP and 10 represents very severe AP.

    A CSBM was defined as a Spontaneous Bowel Movement (SBM) that was associated with a sense of complete evacuation.



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 Bowl Movement (SBM) Frequency Rate [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    The number of Spontaneous Bowl Movements experienced per week.

  • 12-Week Stool Consistency [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    The consistency of each BM was assessed by patients using the 7-point Bristol Stool Form Scale (BSFS) from 1 to 7.

    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 Change in Abdominal Pain Score [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.

  • 12-Week Change in Abdominal Discomfort [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Abdominal Discomfort is measured on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe."

  • 12-Week Change in Bloating [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Bloating was assessed on an 11-point scale where a value of 0 is "none" and a value of 10 is "very severe".

  • Complete Spontaneous Bowl Movement (CSBM) Responder for 6 Weeks Out of 12 Weeks of Treatment [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    A patient is considered to be a CSBM responder if, for at least 6 out of the 12 weeks of the treatment period, an increase of at least 1 CSBM per week from baseline was experienced.

  • Abdominal Pain Responder for 6 Out of 12 Weeks [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    A patient is considered to be an abdominal pain responder if, for at least 6 out of the 12 weeks of the treatment period, they experienced a decrease of 30 percent or more in the abdominal pain score from baseline.

    The Abdominal Pain score assesses the worst of a patient's abdominal pain in the past 24 hours using an 11-point scale (from 0-10), where 0 represents no abdominal pain and 10 represents very severe abdominal pain.


  • 12-Week Percent of Abdominal Pain-free (APF) Days [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    Abdominal pain free (APF) days are those days where the patient reported a score of '0' for abdominal pain at its worst

    Abdominal Pain at its worst (in the last 24 hours) is based on an 11-point scale where 0 represents no abdominal pain and 10 represents very severe abdominal pain.



Enrollment: 803
Study Start Date: July 2009
Study Completion Date: August 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linaclotide
Linaclotide 290 micrograms
Drug: Linaclotide 290 micrograms
Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study
Placebo Comparator: Placebo
Matching placebo
Drug: Matching 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 meets protocol criteria for IBS: reports abdominal discomfort or pain that has two or more of the following three features:

    1. Relieved with defecation
    2. Onset associated with a change in frequency of stool
    3. Onset associated with a change in form (appearance) of stool
  • Patient reports < 3 bowel movements (BMs) per week (in the absence of any laxative, suppository, or enema use during the preceding 24 hours) and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during > 25% of BMs
  • Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests (some patients may require a colonoscopy per American Gastroenterological Association (AGA) guidelines)
  • Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting of BM habits and IBS symptoms

Exclusion Criteria:

  • Patient has history of loose or watery stools for >25% of BMs
  • Patient has a structural abnormality of the gastrointestinal (GI) tract or a history of a disease or condition that can affect GI motility
  • Patient has any protocol-excluded or clinically significant medical or surgical history or concomitant medication use 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: NCT00948818

  Show 118 Study Locations
Sponsors and Collaborators
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
Investigators
Study Director: Paul F.C. Eng, PhD Forest Research Institute, a subsidiary of Forest Laboratories Inc.
  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: NCT00948818     History of Changes
Other Study ID Numbers: LIN-MD-31
Study First Received: July 28, 2009
Results First Received: September 28, 2012
Last Updated: December 19, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Forest Laboratories:
Irritable Bowel Syndrome
Constipation
Linaclotide

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Constipation
Syndrome
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Signs and Symptoms, Digestive
Signs and Symptoms
Disease
Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2014