Phase 4
N=826
An Open-Label, Long-term Study to Assess the Immunogenicity of LINZESS® (Linaclotide) Administered Orally to Adult Participants With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation
Irritable Bowel Syndrome With Constipation · Chronic Idiopathic Constipation
Bottom Line
View on ClinicalTrials.gov: NCT02590432 ↗Enrolled (actual)
826
Serious AEs
2.7%
Results posted
Aug 2019
Primary outcome: Primary: Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum — 3; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Linaclotide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Forest Laboratories
- Primary completion
- Feb 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum |
3; 1 | — |
| SECONDARY Change From Baseline in Participant's Assessment of Constipation Severity |
3.5; 3.4; -1.1; -1.2; -1.3; -1.3 | — |
| SECONDARY Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C) |
3.4; -1.0; -1.1; -1.2; -1.2; -1.2 | — |
| SECONDARY Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C |
4.2; -1.4; -1.6; -1.8; -1.8; -1.9 | — |
| SECONDARY IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C |
3.3; 3.6; 3.7; 3.7; 3.7; 3.8 | — |
| SECONDARY Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC) |
3.4; 3.5; 3.7; 3.8; 3.9; 4.0 | — |
| SECONDARY Number of Participants With Recurrence of Diarrhea |
11; 12; 5; 19; 18 | 1.0000 |
| SECONDARY Number of Participants With Recurrence of Intolerable Diarrhea |
10; 11; 4; 19; 17 | 1.0000 |
| SECONDARY Percentage of Participants With Treatment Emergent Adverse Events (TEAE) |
62.6; 66.0 | — |
| SECONDARY Time to First Recurrence of Diarrhea |
19.0; 15.0; NA; 4.0; 9.0 | 0.9930 |
| SECONDARY Time to First Recurrence of Intolerable Diarrhea |
19.0; 18.0; NA; 8.0; 9.0 | 0.9519 |
Summary
The primary objective of this study is to assess the potential of LINZESS® (linaclotide) treatment to induce the development of anti-drug antibodies (ADAs). The secondary objectives are to provide additional evidence supporting the long-term safety and efficacy of linaclotide in adult irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) participants and to evaluate lower doses of linaclotide.
Eligibility Criteria
Inclusion Criteria
- Participants meet the Rome III criteria for IBS-C or CIC:
- IBS-C Criteria: the participant must meet the following 2 criteria (A and B).
A. IBS Criteria: The participant must have abdominal pain or discomfort at least 3 days per month in the 3 months before diagnosis (with symptom onset at least 6 months before diagnosis) associated with 2 or more of the following:
- Improvement with defecation.
- Onset associated with a change in frequency of stool.
- Onset associated with a change in form (appearance) of stool. B. Stool Consistency Requirement: During the 3 months before diagnosis in the absence of laxative or enema use, the patient has hard or lumpy stools (Bristol Stool Form Scale [BSFS] score 1 or 2) with at least 25% of bowel movements (BMs) and has loose or mushy stools (BSFS 5 or 6) with <25% of BMs.
- CIC Criteria: the participant must meet the following 3 criteria (A, B, and C):
A. Participant meets 2 or more of the following criteria for 3 months before the diagnosis with symptom onset at least 6 months before diagnosis:
- Straining during at least 25% of defecations.
- Lumpy or hard stools in at least 25% of defecations.
- Sensation of incomplete evacuation for at least 25% of defecations.
- Sensation of anorectal obstruction/blockage for at least 25% of defecations.
- Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor).
- Fewer than 3 defecations per week. B. Loose stools are rarely present without the use of laxatives. C. Insufficient criteria for irritable bowel syndrome. (The criteria for IBS are provided in Point A under IBS Criteria, above).
- Participant meets the colonoscopy requirements, which are modified from the Summary of the US-Multi-Society Task Force on Colorectal Cancer and other Colonoscopy Requirements.
- Participant has successfully completed protocol procedures (with no clinically significant findings).
Exclusion Criteria
- At Day 1 visit, the participant reports having 6 or more spontaneous bowel movements (SBMs) in the week prior to screening.
- At Day 1 visit, the participant reports having any SBMs that were watery (BSFS=7) or more than 1 SBM that was mushy (BSFS=6) in the week prior to screening.
- Participant has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility.
- Participant 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.
- Participant has ever received linaclotide as a treatment (including commercially-available product) or has been randomized into any clinical study in which linaclotide was a treatment. (participant who enrolled into linaclotide clinical studies conducted prior or during this study but failed to be randomized are eligible for the current study).
- Participant has ever received plecanatide, SP-333, or has participated in a plecanatide clinical study.
Data sourced from ClinicalTrials.gov (NCT02590432). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.