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NCT02559206

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

Completed Phase 2 Results posted Last updated 24 April 2020
What this trial tests

Phase 2 trial testing Linaclotide in Irritable Bowel Syndrome With Constipation in 759 participants. Completed in 30 September 2016.

Timeline
22 October 2015
Primary endpoint
30 September 2016
30 September 2016

Quick facts

Lead sponsorIronwood Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment759
Start date22 October 2015
Primary completion30 September 2016
Estimated completion30 September 2016
Sites71 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Ironwood Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Irritable Bowel Syndrome With Constipation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR1 or IR vs. Placebo Primary · Baseline, 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.

GroupValue95% CI
Placebo-1.370± 0.241
Linaclotide IR 290 μg-1.938± 0.241
Linaclotide DR1 30 μg-1.667± 0.234
Linaclotide DR1 100 μg-1.656± 0.240
Linaclotide DR1 300 μg-2.140± 0.236
Change From Baseline in Weekly Abdominal Pain Score Over the 12-Week Treatment Period: DR2 or IR vs. Placebo Primary · Baseline, 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.

GroupValue95% CI
Placebo-1.370± 0.241
Linaclotide IR 290 μg-1.938± 0.241
Linaclotide DR2 30 μg-1.825± 0.238
Linaclotide DR2 100 μg-1.669± 0.235
Linaclotide DR2 300 μg-1.628± 0.239
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR1 or IR vs. Placebo Primary · Baseline, up to Week 12

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

GroupValue95% CI
Placebo1.115± 0.285
Linaclotide IR 290 μg2.107± 0.286
Linaclotide DR1 30 μg1.163± 0.278
Linaclotide DR1 100 μg1.414± 0.283
Linaclotide DR1 300 μg1.776± 0.279
Change From Baseline in Weekly CSBM Frequency Rate Over the 12-Week Treatment Period: DR2 or IR vs. Placebo Primary · Baseline, up to Week 12

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

GroupValue95% CI
Placebo1.115± 0.285
Linaclotide IR 290 μg2.107± 0.286
Linaclotide DR2 30 μg1.275± 0.282
Linaclotide DR2 100 μg1.019± 0.278
Linaclotide DR2 300 μg0.869± 0.282
Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR1 or IR vs. Placebo Primary · up 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 comple

Responder
GroupValue95% CI
Placebo14
Linaclotide IR 290 μg21
Linaclotide DR1 30 μg18
Linaclotide DR1 100 μg17
Linaclotide DR1 300 μg26
Non-Responder
GroupValue95% CI
Placebo52
Linaclotide IR 290 μg45
Linaclotide DR1 30 μg49
Linaclotide DR1 100 μg50
Linaclotide DR1 300 μg41
Number of 6/12 Week Abdominal Pain and Constipation (APC) +1 Responders Over the 12-Week Treatment Period: DR2 or IR vs. Placebo Primary · up 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 comple

Responder
GroupValue95% CI
Placebo14
Linaclotide IR 290 μg21
Linaclotide DR2 30 μg16
Linaclotide DR2 100 μg16
Linaclotide DR2 300 μg14
Non-Responder
GroupValue95% CI
Placebo52
Linaclotide IR 290 μg45
Linaclotide DR2 30 μg51
Linaclotide DR2 100 μg50
Linaclotide DR2 300 μg52

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug through Week 12/End-of-Treatment Period Visit (Day 85+3). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 1/66 (2%)
Deaths: 0/66
Linaclotide IR 290 μg
Serious: 1/66 (2%)
Deaths: 0/66
Linaclotide DR1 30 μg
Serious: 0/67 (0%)
Deaths: 0/67
Linaclotide DR1 100 μg
Serious: 0/67 (0%)
Deaths: 0/67
Linaclotide DR1 300 μg
Serious: 0/67 (0%)
Deaths: 0/67
Linaclotide DR2 30 μg
Serious: 0/67 (0%)
Deaths: 0/67
Linaclotide DR2 100 μg
Serious: 0/66 (0%)
Deaths: 0/66
Linaclotide DR2 300 μg
Serious: 0/66 (0%)
Deaths: 0/66

Serious adverse events (3 terms)

ReactionSystemPlaceboLinaclotide IR 290 μgLinaclotide DR1 30 μgLinaclotide DR1 100 μgLinaclotide DR1 300 μgLinaclotide DR2 30 μgLinaclotide DR2 100 μgLinaclotide DR2 300 μg
PneumoniaInfections and infestations
SepsisInfections and infestations
GastroenteritisInfections and infestations
Other adverse events (2 terms — click to expand)

ReactionSystemPlaceboLinaclotide IR 290 μgLinaclotide DR1 30 μgLinaclotide DR1 100 μgLinaclotide DR1 300 μgLinaclotide DR2 30 μgLinaclotide DR2 100 μgLinaclotide DR2 300 μg
DiarrheaGastrointestinal disorders
HeadacheNervous system disorders

Most-reported serious reactions: Pneumonia, Sepsis, Gastroenteritis.

Data from ClinicalTrials.gov NCT02559206 adverse events section.

Sponsor's own description

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).

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation.
    Chey WD, Sayuk GS, Bartolini W, Reasner DS, et al · · 2021 · cited 18× · PMID 33065589 · DOI 10.14309/ajg.0000000000000967
  2. Linaclotide Reduced Response Time for Irritable Bowel Syndrome With Constipation Symptoms: Analysis of 4 Randomized Controlled Trials.
    Brenner DM, Lacy BE, Ford AC, Bartolini W, et al · · 2023 · cited 13× · PMID 36227782 · DOI 10.14309/ajg.0000000000002064
  3. Psychometric Analysis of the Abdominal Score From the Diary for Irritable Bowel Syndrome Symptoms-Constipation Using Phase IIb Clinical Trial Data.
    Coon CD, Hanlon J, Abel JL, Lundy JJ, et al · · 2020 · cited 10× · PMID 32197732 · DOI 10.1016/j.jval.2020.01.002

Verify or expand the search:

Other trials of Linaclotide

Trials testing the same drug.

Other recruiting trials for Irritable Bowel Syndrome With Constipation

Currently open trials in the same condition.

Other Ironwood Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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