Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating

This study has been completed.
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT01642914
First received: July 13, 2012
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to evaluate the efficacy and safety of linaclotide compared with placebo in patients with chronic constipation (CC) and prominent abdominal bloating. This study includes an up to 3-week screening period and a 2-3 week pretreatment period. Patients who are eligible will be randomized to one of two doses of linaclotide or placebo for 12 weeks. This 12-week study will assess the effects of linaclotide on bowel movement frequency, as well as other abdominal and bowel symptoms of CC.


Condition Intervention Phase
Chronic Constipation
Drug: Linaclotide 290 micrograms
Drug: Linaclotide 145 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: Phase 3b, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Chronic Constipation and Prominent Abdominal Bloating at Baseline

Resource links provided by NLM:


Further study details as provided by Forest Laboratories:

Primary Outcome Measures:
  • 9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder [ Time Frame: 12-week treatment period ] [ Designated as safety issue: No ]
    A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.


Secondary Outcome Measures:
  • Change from baseline in Abdominal Bloating [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS)

  • Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS) [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    A patient's 12-week CSBM frequency rate will be the CSBM rate (CSBMs/week) calculated over the 12-weeks of the Treatment Period.

  • Change from baseline Spontaneous Bowel Movement (SBM) Frequency Rate [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    A patient's 12-week SBM frequency rate will be the SBM rate (SBMs/week) calculated over the 12-weeks of the Treatment Period.

  • Change from baseline in Stool Consistency [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Bristol Stool Form Scale will be used by the patient to determine stool consistency

  • Change from baseline in Severity of Straining [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Severity of straining will be measured using a five-point ordinal scale.

  • Change from baseline in Constipation Severity [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Constipation severity will be measured weekly using a five-point ordinal scale.

  • Change from baseline in the Number of Days with a Spontaneous Bowel Movement ( SBM) [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    calculated as number of days with at least 1 Spontaneous Bowel Movement (SBM) during the Treatment Period divided by treatment duration of the patient multiplied by 7

  • Percentage change from baseline in Abdominal Bloating [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Abdominal Bloating will be measured daily using an 11-point Numerical Rating Scale (NRS)

  • Spontaneous Bowel Movement (SBM) within 24 hours after the first dose of investigational product [ Time Frame: reported within 24 hours of patient's first dose of investigational product ] [ Designated as safety issue: No ]
    A patient considered a responder if he/she has at least 1 Spontaneous Bowel Movement (SBM) within 24 hours after taking the first dose of investigational product

  • Complete Spontaneous Bowel Movement (CSBM) + 1 Responder [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    CSBM +1 Responder is a patient who has an increase in the 12 week CSBM Frequency Rate of 1 or more from baseline over the Treatment Period.

  • Abdominal Bloating 30% Responder [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    12-Week Abdominal Bloating 30% Responder is a patient who has an improvement in his/her 12-week abdominal bloating score of at least 30% compared to baseline.

  • Change in baseline in Abdominal Discomfort [ Time Frame: calculated daily over the 12 weeks of the patient's Treatment Period. ] [ Designated as safety issue: No ]
    Abdominal Discomfort will be measured daily using an 11-point Numerical Rating Scale (NRS)

  • Time to First Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product [ Time Frame: number of hours from the time of the first dose of investigational product ] [ Designated as safety issue: No ]
    Time to First SBM after First Dose of Investigational Product is defined as the number of hours elapsing from the time of the first dose of investigational product is taken to the occurrence of the first SBM


Enrollment: 487
Study Start Date: August 2012
Study Completion Date: August 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Linaclotide 290 micrograms
Linaclotide 290 micrograms
Drug: Linaclotide 290 micrograms
oral capsule, taken once daily each morning at least 30 minutes before breakfast
Experimental: Linaclotide 145 Micrograms
Linaclotide 145 micrograms
Drug: Linaclotide 145 micrograms
oral capsule, taken once daily each morning at least 30 minutes before breakfast
Placebo Comparator: Placebo
Matching placebo
Drug: Matching placebo
oral capsule, taken once daily each morning at least 30 minutes before breakfast

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patient has completed a colonoscopy according to the American Gastroenterological Association criteria with no clinically significant findings
  • Patient has successfully completed protocol procedures (with no clinically significant findings)
  • Patient meets protocol criteria for Chronic Constipation(CC): < 3 bowel movements per week and reports one or more of the following symptoms for at least 12 weeks:

    1. Straining during more than 25% of BMs
    2. Lumpy or hard stools during more than 25% of BMs
    3. Sensation of incomplete evacuation during more than 25% of BMs
  • Patient demonstrates continued chronic constipation and bloating through Pretreatment Period
  • Patient is compliant with Interactive voice response System (IVRS)

Exclusion Criteria:

  • Patient has a 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 would limit the patient's ability to complete or participate in this clinical trial or 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: NCT01642914

  Show 151 Study Locations
Sponsors and Collaborators
Forest Laboratories
Ironwood Pharmaceuticals, Inc.
Investigators
Study Director: Paul F. Eng, PhD Forest Laboratories
  More Information

No publications provided

Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01642914     History of Changes
Other Study ID Numbers: LIN-MD-04
Study First Received: July 13, 2012
Last Updated: September 30, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Forest Laboratories:
Chronic Constipation
Abdominal Bloating
Linaclotide

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

ClinicalTrials.gov processed this record on August 20, 2014