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Trial record 1 of 1 for:    MCP-103-312 | United States
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A Trial of Linaclotide 290 μg in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

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ClinicalTrials.gov Identifier: NCT03573908
Recruitment Status : Completed
First Posted : June 29, 2018
Results First Posted : November 16, 2020
Last Update Posted : December 1, 2020
Sponsor:
Collaborator:
Allergan Sales, LLC
Information provided by (Responsible Party):
Ironwood Pharmaceuticals, Inc.

Brief Summary:
To evaluate the efficacy on abdominal symptoms (abdominal bloating, abdominal discomfort, and abdominal pain) and safety of linaclotide 290 μg administered orally to patients with IBS-C.

Condition or disease Intervention/treatment Phase
Irritable Bowel Syndrome Characterized by Constipation Drug: Linaclotide Drug: Placebo Phase 3

Detailed Description:
This study consists of a 12-week Treatment Period followed by 4-week Randomized Withdrawal (RW) Period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 614 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3b, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial of Linaclotide 290 μg Administered Orally for 12 Weeks Followed by a 4-week Randomized Withdrawal Period in Patients With Irritable Bowel Syndrome With Constipation
Actual Study Start Date : June 20, 2018
Actual Primary Completion Date : March 13, 2019
Actual Study Completion Date : April 10, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Linaclotide 290 µg
Participants receive linaclotide 290 µg orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are rerandomized to receive either linaclotide 290 µg or placebo for 4 weeks in the Randomized Withdrawal Period.
Drug: Linaclotide
Oral capsule
Other Name: Linzess

Drug: Placebo
Matching placebo oral capsule

Placebo Comparator: Placebo
Participants receive placebo to linaclotide orally once daily for 12 weeks during the Treatment Period. At Week 12 participants are switched to receive linaclotide 290 µg for 4 weeks during the Randomized Withdrawal Period.
Drug: Linaclotide
Oral capsule
Other Name: Linzess

Drug: Placebo
Matching placebo oral capsule




Primary Outcome Measures :
  1. Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period [ Time Frame: Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12) ]
    A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.


Secondary Outcome Measures :
  1. Cumulative Distribution of Change From Baseline in 12-Week Abdominal Score [ Time Frame: Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12) ]
    A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The 12-week abdominal score was the average of the non-missing abdominal scores reported over the course of the treatment period. Change from baseline (BL) was calculated as the 12-week score minus the baseline score. The table presents the percentage of participants whose 12-week change from baseline was less than or equal to the threshold value of the score change (cumulative distribution of change).

  2. Percentage of 6/12 Week Abdominal Score Responders (Responder Rate) [ Time Frame: Baseline (14 days before randomization up to the time of randomization), Treatment Period (Weeks 1-12) ]

    A 6/12 week abdominal score responder is a participant who meets the weekly abdominal score responder criteria for at least 6 out of the 12 weeks of the Treatment Period. For each week in the Treatment Period, a weekly abdominal score responder is a participant who has an improvement from baseline of at least 2 points (ie, a -2 point change from baseline) in the respective weekly abdominal score. If a participant did not have at least 4 completed eDiary entries for a particular Treatment Period week, the participant was not considered a responder for that week.

    A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period.


  3. Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Over Time in the Treatment Period [ Time Frame: Baseline (14 days before randomization up to the time of randomization), Weeks 1-12 ]
    A participant's daily abdominal score was calculated as the average of daily e-diary abdominal pain, abdominal bloating and abdominal discomfort scores, each based on an 11-point scale of 0 (none) and 10 (worst possible). Baseline abdominal score was derived from the eDiary data collected daily in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization. The participant's abdominal score was averaged on a weekly basis, and each weekly change from baseline was calculated for the treatment period and used as the dependent variable in the mixed model with repeated measures (MMRM) model. MMRM results are based on a model with treatment, analysis week, region and treatment-by-week interaction as fixed effects and baseline as a covariate. An unstructured covariance structure was used to model intra-subject correlation with subjects as a random effect.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has no clinically significant findings on a physical examination and clinical laboratory tests
  • Female patients of childbearing potential must agree to use one of the following methods of birth control:

    1. Hormonal contraception
    2. Double-barrier birth control
    3. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy
  • Patient meets protocol criteria for diagnosis of IBS-C
  • Patient demonstrates continued IBS-C symptoms through Pretreatment Period
  • Patient maintains a minimum level of compliance with daily diary

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03573908


Locations
Show Show 79 study locations
Sponsors and Collaborators
Ironwood Pharmaceuticals, Inc.
Allergan Sales, LLC
Investigators
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Study Chair: Wilmin Bartolini, PhD Ironwood Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Ironwood Pharmaceuticals, Inc.:
Study Protocol  [PDF] March 26, 2018
Statistical Analysis Plan  [PDF] November 27, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03573908    
Other Study ID Numbers: MCP-103-312
First Posted: June 29, 2018    Key Record Dates
Results First Posted: November 16, 2020
Last Update Posted: December 1, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Irritable Bowel Syndrome
Syndrome
Constipation
Disease
Pathologic Processes
Signs and Symptoms, Digestive
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Linaclotide
Guanylyl Cyclase C Agonists
Enzyme Activators
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents