Randomized, Double-blind, Dose-range-finding, Phase 2 Study of Linaclotide Administered to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00460811
First received: April 13, 2007
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determine the safety, efficacy, and dose response of a range of oral doses of linaclotide administered to patients meeting criteria for IBS-C.


Condition Intervention Phase
Irritable Bowel Syndrome With Constipation
Drug: Linaclotide Acetate
Drug: Matching placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-design, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Irritable Bowel Syndrome With Constipation

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in the Weekly Normalized Complete Spontaneous Bowel Movement (CSBM) Rate During Weeks 1 Through 12 of the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]

    The change in the weekly normalized CSBM Rate during Weeks 1 through 12 of the Treatment Period from the weekly normalized CSBM Rate obtained during the Pretreatment Period.

    The CSBM rate was normalized based on the number of CSBMs occurring in that week, adjusting for differences in the duration of the week and black-out periods (time not covered due to a missed IVRS call) versus 7x24 hours.



Secondary Outcome Measures:
  • CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate) [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    For each week of the Treatment and Posttreatment Periods, a patient was considered a CSBM Responder if for that week the patient 1) completed ≥ 4 days of IVRS questions, 2) had a CSBM rate of ≥ 3 for the week, and 3) had an increase in CSBM rate of ≥ 1 from the baseline weekly CSBM rate.

  • Change From Baseline in the Weekly Normalized SBM Rate for the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    SBMs were measured daily during the treatment period by patient calls to the IVRS.

  • Change From Baseline in Stool Consistency (7-point Ordinal BSFS) for the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Stool consistency analyses were performed using the 7-point Bristol Stool Form Scale (BSFS), whereby a score of 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; and 7 = watery, no solid pieces (entirely liquid).

  • Change From Baseline in Straining (5-point Ordinal Scale) for the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Straining was assessed using a 5-point ordinal scale, whereby a score of 1 = not at all, 2 = a little bit, 3 = a moderate amount, 4 = a great deal, and 5 = an extreme amount.

  • Change From Baseline in Degree of Relief of Irritable Bowel Syndrome (IBS) Symptoms (7-point Balanced Scale) for the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    Patients provided a weekly assessment of Degree of Relief of IBS Symptoms using a 7-point balanced scale (1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse, 7=as bad as I can imagine).

  • Change From Baseline in Abdominal Pain (5-point Ordinal Scale) for the Treatment Period [ Time Frame: Change from Baseline to Week 12 ] [ Designated as safety issue: No ]
    During the study, patients provided their self assessment of abdominal pain using a 5-point ordinal scale (1=none, 2=mild, 3=moderate, 4=severe, 5=very severe


Enrollment: 420
Study Start Date: April 2007
Study Completion Date: April 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 72 ug linaclotide acetate Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 145 ug linaclotide acetate Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 290 ug linaclotide acetate Drug: Linaclotide Acetate
Oral, once daily
Active Comparator: 579 ug linaclotide acetate Drug: Linaclotide Acetate
Oral, once daily
Placebo Comparator: Matching Placebo Drug: Matching placebo
Oral, once daily

  Eligibility

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

Inclusion Criteria:

  • Must not be pregnant or breastfeeding and agree to use birth control;
  • Completion of a negative colonoscopy as per American Gastroenterology Association (AGA) criteria and no clinically-significant laboratory or physical examination findings;
  • Meets protocol-defined criteria for IBS-C, including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria;
  • Demonstrates English fluency and has access to a touch-tone telephone.

Exclusion Criteria:

  • Recent history of mushy or watery stools;
  • Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study;
  • Clinically-significant alarm symptoms;
  • Secondary causes of constipation or evacuation disorders;
  • Surgery to the gastrointestinal tract;
  • Usage of prohibited medications.
  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: NCT00460811

  Show 85 Study Locations
Sponsors and Collaborators
Ironwood Pharmaceuticals, Inc.
Investigators
Study Director: Microbia Medical Director, MD Microbia, 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: NCT00460811     History of Changes
Other Study ID Numbers: MCP-103-202
Study First Received: April 13, 2007
Results First Received: September 28, 2012
Last Updated: January 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ironwood Pharmaceuticals, Inc.:
Irritable Bowel Syndrome with Constipation
IBS
Irritable Bowel Syndrome
linaclotide acetate
linaclotide
MD-1100

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 31, 2014