A Trial of Linaclotide 290 μg in Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Phase 3

Completed

Conditions: Irritable Bowel Syndrome Characterized by Constipation

Interventions: Drug: Linaclotide
Drug: Placebo

Registration Number: NCT03573908

Lead Sponsor: 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 614

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linaclotide 290 µg	Placebo	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.
Placebo	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.
Linaclotide 290 µg	Linaclotide	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.
Placebo	Linaclotide	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.

Primary Outcome Measures

Name	Time	Method
Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Throughout the Treatment Period	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

Name	Time	Method
Overall Change From Baseline in Abdominal Score (Abdominal Bloating, Abdominal Discomfort, and Abdominal Pain) Over Time in the Treatment Period	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.
Cumulative Distribution of Change From Baseline in 12-Week Abdominal Score	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).
Percentage of 6/12 Week Abdominal Score Responders (Responder Rate)	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.

Trial Locations

Locations (77): Clinical Research Associates
🇺🇸
Huntsville, Alabama, United States
Elite Clinical Studies
🇺🇸
Phoenix, Arizona, United States
Adobe Clinical Research, LLC
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Tucson, Arizona, United States
Arkansas Gastroenterology
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North Little Rock, Arkansas, United States
GW Research, Inc.
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Chula Vista, California, United States
Kindred Medical Institute for Clinical Trials, LLC
🇺🇸
Corona, California, United States
Diagnamics, Inc.
🇺🇸
Encinitas, California, United States
MD Studies, Inc.
🇺🇸
Fountain Valley, California, United States
Paragon Rx Clinical, Inc. - Garden Grove
🇺🇸
Garden Grove, California, United States
Grossmont Center For Clinical Research
🇺🇸
La Mesa, California, United States
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Clinical Research Associates
🇺🇸Huntsville, Alabama, United States