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

Phase 2
Completed
Conditions
Irritable Bowel Syndrome With Constipation
Interventions
Drug: Matching Placebo
Registration Number
NCT02559206
Lead Sponsor
Ironwood Pharmaceuticals, Inc.
Brief Summary

The objectives of this study are to evaluate the safety, efficacy, and dose response of two delayed release formulations of linaclotide (DR; DR formulation 1 is DR1; DR formulation 2 is DR2) administered orally to patients with irritable bowel syndrome with constipation (IBS-C). Additional objectives include understanding how the two DR formulations compare with each other and with the FDA-approved 290 μg LINZESS® (the immediate release \[IR\] formulation of linaclotide).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
759
Inclusion Criteria
  • Patient has completed a colonoscopy according to the American Gastroenterological Association (AGA) criteria, with no clinically significant findings
  • Patient has no clinically significant findings on a physical examination and clinical laboratory tests
  • Patient meets protocol criteria for diagnosis of IBS-C
  • Patient demonstrates continued IBS-C 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
GroupInterventionDescription
100 μg linaclotide DR1 and placeboLinaclotide-
300 μg linaclotide DR1 and placeboLinaclotide-
30 μg linaclotide DR2 and placeboLinaclotide-
290 μg linaclotide IR and placeboLinaclotide-
30 μg linaclotide DR1 and placeboLinaclotide-
100 μg linaclotide DR2 and placeboLinaclotide-
300 μg linaclotide DR2 and placeboLinaclotide-
PlaceboMatching Placebo-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. PlaceboBaseline, up to Week 12

Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.

Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. PlaceboBaseline, up to Week 12

A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placeboup to Week 12

A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period.

* Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder.

* Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week.

* Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week.

A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.

Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placeboup to Week 12

A 6/12 Week APC +1 Responder is a participant who meets the Weekly APC +1 Responder criteria for at least 6 out of the 12 weeks of the Treatment Period.

* Weekly APC +1 Responder: A participant who meets the criteria to be a Weekly Abdominal Pain Responder and a Weekly CSBM +1 Responder.

* Weekly Abdominal Pain Responder: A participant who has a decrease from baseline of ≥30% in the mean daily worst abdominal pain scores for that week.

* Weekly CSBM +1 Responder: A participant who has an increase from baseline of ≥1 in the CSBM weekly rate for that week.

A participant with \<4 days of completed eDiary data for that week is not considered a responder for that week.

Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. PlaceboBaseline, up to Week 12

A participant's weekly CSBM frequency rate is the CSBM rate (CSBMs/week) calculated over that week.

Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. PlaceboBaseline, up to Week 12

Abdominal pain assessment was based on an 11-point numerical rating scale (0=No symptom; 10=Worst possible) assessing the symptom "at its worst in past 24 hours." A participant's weekly abdominal pain score is the average of the nonmissing abdominal pain scores reported by the participant during each week.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Ironwood Investigational Site

🇺🇸

La Crosse, Wisconsin, United States

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