Trial of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00938717
First received: July 12, 2009
Last updated: October 9, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine the safety and efficacy of linaclotide administered to patients with Irritable Bowel Syndrome with Constipation (IBS-C).


Condition Intervention Phase
Irritable Bowel Syndrome With Constipation
Drug: Linaclotide or Matching Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide Administered Orally for 26 Weeks in Patients With Irritable Bowel Syndrome With Constipation

Resource links provided by NLM:


Further study details as provided by Ironwood Pharmaceuticals, Inc.:

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

    The AP score assesses patient's worst 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.

    SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM 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 patient's worst 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 to be a 6 out of 12 week APC responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had an increase of at least 1 CSBM from baseline, and had a decrease of at least 30 percent in their Abdominal Pain (AP) score from baseline during a particular week.

    The AP score assesses patient's worst 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.

    SBM is defined as a bowel movement that occurs in the absence of laxative, enema, or suppository use on either the calendar day of the bowel movement or the calendar day before the bowel movement. CSBM is defined as an SBM associated with a sense of complete evacuation.



Secondary Outcome Measures:
  • 12-Week Complete Spontaneous Bowel Movement (CSBM) Frequency [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    The change from baseline in 12-week CSBM frequency (i.e., weekly CSBM frequency over the first 12 weeks of the Treatment Period).

  • 12-Week Spontaneous Bowl Movement (SBM) Frequency [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    The change from baseline in 12-week SBM frequency (i.e., weekly SBM frequency over the first 12 weeks of the Treatment Period).

  • 12-Week Change in 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 Change in 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 was assessed 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 AP responder if, for at least 6 out of the first 12 weeks of the treatment period, the patient had a decrease of at least 30 percent in their Abdominal Pain score from baseline during a particular week.

  • 12-Week Percent of Abdominal Pain-free 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: 805
Study Start Date: July 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Linaclotide or Matching Placebo
Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial
Experimental: 290 μg Linaclotide Drug: Linaclotide or Matching Placebo
Linaclotide or Matching Placebo, administered orally, once daily, for the duration of the trial

  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 diagnosis of IBS-C
  • Patient demonstrates continued IBS-C 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 a medical condition that may contribute to abdominal pain
  • 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: NCT00938717

  Show 107 Study Locations
Sponsors and Collaborators
Ironwood Pharmaceuticals, Inc.
Forest Laboratories
Investigators
Study Chair: Jeffrey M. Johnston, MD, FACP Ironwood Pharmaceuticals, Inc.
  More Information

No publications provided by Ironwood Pharmaceuticals, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00938717     History of Changes
Other Study ID Numbers: MCP-103-302
Study First Received: July 12, 2009
Results First Received: September 28, 2012
Last Updated: October 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ironwood Pharmaceuticals, Inc.:
IBS

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

ClinicalTrials.gov processed this record on July 28, 2014