Dose-range-finding, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00402337
First received: November 18, 2006
Last updated: January 29, 2013
Last verified: January 2013
  Purpose

The primary purpose of this study is to evaluate the efficacy and safety of administration of linaclotide acetate in patients with chronic constipation.


Condition Intervention Phase
Chronic Constipation
Drug: linaclotide acetate
Drug: Matching placebo
Phase 2

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 Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-group, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Pretreatment in Weekly Normalized Spontaneous Bowel Movement (SBM) Frequency [ Time Frame: Change from Baseline to Week 4 ] [ Designated as safety issue: No ]
    Change in SBM frequency during Weeks 1 through 4 of the treatment period from the weekly SBM rate obtained during the pretreatment period.


Secondary Outcome Measures:
  • SBM 75% Responder for the Treatment Period (Based on the Normalized Rate) [ Time Frame: Change from Baseline to Week 4 ] [ Designated as safety issue: No ]

    A patient was an SBM 75% Responder if the patient was an SBM Responder for ≥3 of the 4 treatment period weeks.

    For each week of the treatment and postreatment periods, a patient was considered an SBM Responder if for that week the patient 1) completed ≥4 days of IVRS questions,2) had an SBM rate of ≥ 3 for the week, and 3) had an increase in SBM rate of ≥ 1 from their baseline weekly SBM rate.


  • CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate) [ Time Frame: Change from Baseline to Week 4 ] [ Designated as safety issue: No ]

    A patient was a complete spontaneous bowel movement (CSBM) 75% Responder if the patient was a CSBM Responder for ≥3 of the 4 treatment period weeks.

    For each week of the treatment and postreatment 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 their baseline weekly CSBM rate.


  • Change From Baseline in the Weekly Normalized CSBM Rate for the Treatment Period [ Time Frame: Change from Baseline to Week 4 ] [ Designated as safety issue: No ]
    CSBMs measured daily during the treatment period. During each daily phone call into the IVRS, patients were asked: How many bowel movements did you have today or yesterday after your last call?

  • Change From Baseline in Stool Consistency (BSFS) Score for the Treatment Period [ Time Frame: Change from Baseline to Week 4 ] [ Designated as safety issue: No ]
    Stool consistency analyses were performed using the 7-point BSFS, whereby a score of 1 = 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 = entirely liquid.

  • Change From Baseline in Straining Score for the Treatment Period [ Time Frame: Change from Baseline to Week 4 ] [ 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.


Enrollment: 310
Study Start Date: November 2006
Study Completion Date: February 2008
Primary Completion Date: December 2007 (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:

  • Patient is 18 years of age or older
  • Patient meets colonoscopy requirements according to the American Gastroenterological Association
  • Patient meets criteria for chronic constipation including weekly bowel movement frequency requirements and reports one or more symptoms of constipation according to protocol requirements
  • Patient has successfully completed study requirements with no clinically-significant findings: physical exam, ECG, clinical laboratory tests
  • Patient is fluent in English

Exclusion Criteria:

  • Patient reports loose or watery stools
  • Patient meets criteria for IBS including protocol-defined abdominal discomfort or pain
  • Patient may not take prohibited medications per protocol
  • Medical diagnoses, medical conditions, or family history that would not make the patient a good candidate for the study or limit the patient's ability to complete the clinical study
  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: NCT00402337

  Show 60 Study Locations
Sponsors and Collaborators
Ironwood Pharmaceuticals, Inc.
Investigators
Study Director: Microbia Medical Affairs 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: NCT00402337     History of Changes
Other Study ID Numbers: MCP-103-201
Study First Received: November 18, 2006
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.:
Constipation
Chronic Constipation
Microbia
linaclotide
linaclotide acetate
MD-1100

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

ClinicalTrials.gov processed this record on September 16, 2014