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Trial · Interventional

CompletedPhase 4Results postedRegistry data

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

NCTNCT02590432 (opens ClinicalTrials.gov in a new tab)Other idLIN-MD-10
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 4
Enrollment
828 participants (actual)
Sponsor
Forest Laboratories · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
1 Nov 2015
Primary completion
5 Feb 2018
Completion
5 Feb 2018
First posted
29 Oct 2015 (estimated)
Last update posted
22 Aug 2019
Conditions
Irritable Bowel Syndrome With Constipation · Chronic Idiopathic Constipation

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20152016201720182019
  1. Ph 4

    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

    NCT02590432

    1 Nov 2015 to 5 Feb 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • LinaclotideDrug

Arms9

  • Experimental

    LINZESS® 145 μg (CIC, Open Label)

    LINZESS® (linaclotide) 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period.

  • Experimental

    LINZESS® 290 μg (IBS-C, Open Label)

    LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period.

  • Experimental

    LINZESS® 290 μg (IBS-C, Double Blind)

    Following participation in the Open Label Treatment Period, LINZESS® 290 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable.

  • Experimental

    LINZESS® 145 μg (IBS-C, Double Blind)

    Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was reduced to Open Label 72 μg, if applicable.

  • Experimental

    LINZESS® 72 μg (IBS-C, Double Blind)

    Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with IBS-C. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable.

  • Experimental

    LINZESS® 145 μg (CIC, Double Blind)

    Following participation in the Open Label Treatment Period, LINZESS® 145 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was reduced to 72 μg, if applicable.

  • Experimental

    LINZESS® 72 μg (CIC, Double Blind)

    Following participation in the Open Label Treatment Period, LINZESS® 72 μg capsules, orally, once daily from double-blind randomization up to Week 52 for participants with CIC. If an intolerable AE occurred, dose was maintained at Open Label 72 μg, if applicable.

  • Experimental

    LINZESS® 72 μg (CIC, Dose-reduced Open Label)

    Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with CIC.

  • Experimental

    LINZESS® 72 μg (IBS-C, Dose-reduced Open Label)

    Following participation in the Double-blind Treatment Period, if an intolerable AE occurred, LINZESS® 72 μg capsules, orally, once daily up to Week 52 for participants with IBS-C.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum

    Time frame · Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks)

    Registry description

    Participants who met either of the following criteria: 1) treatment-induced ADA-positive (≥ 1 postbaseline ADA-positive sample) for baseline ADA negative or ADA-undetermined participants or 2) treatment-boosted ADA-positive (≥ 1 postbaseline ADA-positive sample with titer values ≥ 4-fold the baseline titer value) for baseline ADA-positive participants were reported as a ADA positive responder.

Secondary outcomes(10)

  1. Change From Baseline in Participant's Assessment of Constipation Severity

    Time frame · Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

    Registry description

    Participants rated constipation severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement.

  2. Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C)

    Time frame · Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

    Registry description

    Participants rated IBS symptoms severity during the previous 7 days on a 5-point ordinal scale where, 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very severe. Higher scores indicate greater severity. A negative change from Baseline indicates improvement.

  3. Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C

    Time frame · Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

    Registry description

    Participants rated degree of relief of IBS symptoms during previous 7 days on a 7-point balanced ordinal scale where, 1=completely relieved, 2=considerably relieved, 3=somewhat relieved, 4=unchanged, 5=somewhat worse, 6=considerably worse and 7=as bad as I can imagine. Lower scores indicate greater relief. A negative change from Baseline indicates improvement.

  4. IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C

    Time frame · Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

    Registry description

    Participants rated degree of satisfaction with the LINZESS®'s ability to relieve IBS symptoms on a 5-point ordinal scale where, 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction.

  5. Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC)

    Time frame · Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

    Registry description

    Participants rated degree of satisfaction with LINZESS®'s ability to relieve constipation symptoms on a 5-point ordinal scale where 1=Not at all satisfied, 2=A little satisfied, 3=Moderately satisfied, 4=Quite satisfied and 5=Very satisfied. Higher scores indicate greater satisfaction.

  6. Number of Participants With Recurrence of Diarrhea

    Time frame · From first dose in the Double-blind Treatment Period to Week 52

    Registry description

    Participant reporting any instance of diarrhea during the Double-blind Treatment Period.

  7. Number of Participants With Recurrence of Intolerable Diarrhea

    Time frame · From first dose in the Double-blind Treatment Period to Week 52

    Registry description

    Participants reporting any instance of intolerable diarrhea during the Double-blind Treatment Period (Non-responder otherwise). Only includes participants reporting intolerable diarrhea during the Open-label Treatment Period.

  8. Percentage of Participants With Treatment Emergent Adverse Events (TEAE)

    Time frame · From first dose of study treatment up to Week 52

    Registry description

    An adverse event is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurred after receiving the first dose of investigational product or an AE present prior to first dose but increased in severity during the Treatment Period.

  9. Time to First Recurrence of Diarrhea

    Time frame · From first dose in the Double-blind Treatment Period to Week 52

    Registry description

    Time to first recurrence of diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period.

  10. Time to First Recurrence of Intolerable Diarrhea

    Time frame · From first dose in the Double-blind Treatment Period to Week 52

    Registry description

    Time to first recurrence of intolerable diarrhea was defined as event/censored date - double-blind start date + 1, where event date (responders) = first recurrence of intolerable diarrhea date during the double-blind treatment period; censoring date (non-responders) = double-blind end date. Only includes participants reporting intolerable diarrhea during the open-label treatment period.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks)

Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum

GroupValue (Participants)
LINZESS® 145 μg (CIC, Open Label)3
LINZESS® 290 μg (IBS-C, Open Label)1
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

Change From Baseline in Participant's Assessment of Constipation Severity

GroupValue (score on a scale)Spread
LINZESS® 145 μg (CIC, Open Label)3.50.8
LINZESS® 290 μg (IBS-C, Open Label)3.40.8
Secondary outcomeMean· Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C)

GroupValue (score on a scale)Spread
LINZESS® 290 μg (IBS-C, Open Label)3.40.7
Secondary outcomeMean· Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C

GroupValue (score on a scale)Spread
LINZESS® 290 μg (IBS-C, Open Label)4.20.8
Secondary outcomeMean· Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C

GroupValue (score on a scale)Spread
LINZESS® 290 μg (IBS-C, Open Label)3.31.2
Secondary outcomeMean· Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)

Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC)

GroupValue (score on a scale)Spread
LINZESS® 145 μg (CIC, Open Label)3.41.2
Secondary outcomeCount of participants· From first dose in the Double-blind Treatment Period to Week 52

Number of Participants With Recurrence of Diarrhea

GroupValue (Participants)
LINZESS® 290 μg (IBS-C, Double Blind)11
LINZESS® 145 μg (IBS-C, Double Blind)12
LINZESS® 72 μg (IBS-C, Double Blind)5
LINZESS® 145 μg (CIC, Double Blind)19
LINZESS® 72 μg (CIC, Double Blind)18
Secondary outcomeCount of participants· From first dose in the Double-blind Treatment Period to Week 52

Number of Participants With Recurrence of Intolerable Diarrhea

GroupValue (Participants)
LINZESS® 290 μg (IBS-C, Double Blind)10
LINZESS® 145 μg (IBS-C, Double Blind)11
LINZESS® 72 μg (IBS-C, Double Blind)4
LINZESS® 145 μg (CIC, Double Blind)19
LINZESS® 72 μg (CIC, Double Blind)17

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
LINZESS® 145 μg (CIC)LINZESS® 145 μg capsules, orally, once daily for up to 52 weeks for participants with CIC. If an Intolerable AE occurred participants could be randomized to the Double-blind Treatment Period (145 μg or 72 μg) or entered the Dose-reduced 72 μg Open Label Period.1 / 50816 / 508133 / 508
LINZESS® 290 μg (IBS-C)LINZESS® 290 μg capsules, orally, once daily for up to 52 weeks for participants with IBS-C. If an intolerable AE occurred participants could be randomized to the Double-blind Treatment Period (290 μg, 145 μg or 72 μg) or entered the Dose-reduced 72 μg Open Label Period.0 / 3186 / 318122 / 318

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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: 1. Improvement with defecation. 2. Onset associated with a change in frequency of stool. 3. 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: 1. Straining during at least 25% of defecations. 2. Lumpy or hard stools in at least 25% of defecations. 3. Sensation of incomplete evacuation for at least 25% of defecations. 4. Sensation of anorectal obstruction/blockage for at least 25% of defecations. 5. Manual maneuvers to facilitate at least 25% of defecations (e.g., digital evacuation, support of the pelvic floor). 6. 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.

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