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 | Completed Phase 4 Results

• 1 other identifier: LIN-MD-10
• Study Type: interventional
• Target: 828
• Locations: 1 country
• Sites: 79

Brief 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.

Conditions

Irritable Bowel Syndrome With Constipation; Chronic Idiopathic Constipation

Keywords

Immunogenicity; Irritable Bowel Syndrome with Constipation; Chronic Idiopathic Constipation; Linaclotide; Linzess

Outcome Measures

Primary Outcomes (1)

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

  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.

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

Secondary Outcomes (10)

• Change From Baseline in Participant's Assessment of Constipation Severity

  Baseline (Day 1) to Weeks 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)

  Baseline (Day 1) to Week 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

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

• IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C

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

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

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

Study Arms (9)

LINZESS® 145 μg (CIC, Open Label)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 290 μg (IBS-C, Open Label)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 290 μg (IBS-C, Double Blind)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 145 μg (IBS-C, Double Blind)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 72 μg (IBS-C, Double Blind)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 145 μg (CIC, Double Blind)

EXPERIMENTAL

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.

Drug: Linaclotide

LINZESS® 72 μg (CIC, Double Blind)

EXPERIMENTAL

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.

Drug: Linaclotide

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

EXPERIMENTAL

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.

Drug: Linaclotide

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

EXPERIMENTAL

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.

Drug: Linaclotide

Interventions

Linaclotide DRUG

Linaclotide capsules, orally, once daily.

Also known as: LINZESS®

LINZESS® 145 μg (CIC, Double Blind); LINZESS® 145 μg (CIC, Open Label); LINZESS® 145 μg (IBS-C, Double Blind); LINZESS® 290 μg (IBS-C, Double Blind); LINZESS® 290 μg (IBS-C, Open Label); LINZESS® 72 μg (CIC, Dose-reduced Open Label); LINZESS® 72 μg (CIC, Double Blind); LINZESS® 72 μg (IBS-C, Dose-reduced Open Label); LINZESS® 72 μg (IBS-C, Double Blind)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Forest Laboratories: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (79)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

North Alabama Research Center, LLC

Athens, Alabama, 35611, United States

Location

Alliance Clinical Research

Childersburg, Alabama, 35044, United States

Location

G & L Research, LLC

Foley, Alabama, 36535, United States

Location

Radiant Research, Inc.

Chandler, Arizona, 85224, United States

Location

Radiant Research, Inc.

Scottsdale, Arizona, 85251, United States

Location

Clinical Research Institute of Arizona, LLC

Surprise, Arizona, 85374, United States

Location

Clinical Research Consortium

Tempe, Arizona, 85283, United States

Location

Desert Sun Clinical Research, LLC.

Tucson, Arizona, 85710, United States

Location

Preferred Research Partners, Inc.

Little Rock, Arkansas, 72211, United States

Location

Applied Research Center of Arkansas

Little Rock, Arkansas, 72212, United States

Location

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, 92879, United States

Location

Global Clinical Trials LLC

Costa Mesa, California, 92627, United States

Location

Diagnamics Inc

Encinitas, California, 92024, United States

Location

MD Studies, Inc.

Fountain Valley, California, 92708, United States

Location

Research Center of Fresno, Inc.

Fresno, California, 93702, United States

Location

VVCRD Clinical Research

Garden Grove, California, 92845, United States

Location

Facey Medical Foundation

Mission Hills, California, 91345, United States

Location

Clinical Trials Research

Sacramento, California, 95821, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Artemis Institute for Clinical Research

San Diego, California, 92103, United States

Location

Precision Research Institute

San Diego, California, 92114, United States

Location

Empire Clinical Research

Upland, California, 91786, United States

Location

Lynn Institute of Denver

Denver, Colorado, 80246, United States

Location

ZASA Clinical Research

Boynton Beach, Florida, 33472, United States

Location

Meridien Research

Bradenton, Florida, 34201, United States

Location

Clinical Research of Brandon LLC

Brandon, Florida, 33511, United States

Location

Clinical Physiology Associates

Fort Myers, Florida, 33912, United States

Location

Direct Helpers Research Center

Hialeah, Florida, 33012, United States

Location

Eastern Research, Inc.

Hialeah, Florida, 33013, United States

Location

Center for Advanced Gastroenterology

Maitland, Florida, 32751, United States

Location

Florida Medical Center and Research, Inc.

Miami, Florida, 33142, United States

Location

Clinical Neuroscience Solutions, Inc

Orlando, Florida, 32801, United States

Location

Accord Clinical Research

Port Orange, Florida, 32129, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

River Birch Research Alliance, LLC

Blue Ridge, Georgia, 30513, United States

Location

North Georgia Clinical Research

Woodstock, Georgia, 30189, United States

Location

Northwest Clinical Trials

Boise, Idaho, 83704, United States

Location

Rockford Gastroenterology Associates

Rockford, Illinois, 611047, United States

Location

Iowa Digestive Center, PC

Clive, Iowa, 50325, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Integrated Clinical Trial Services, Inc.

West Des Moines, Iowa, 50265, United States

Location

Heartland Research Associates, LLC

Newton, Kansas, 67114, United States

Location

Health Science Research Center

Pratt, Kansas, 67124, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67205, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67207, United States

Location

KAMP Medical Research Inc

Natchitoches, Louisiana, 71457, United States

Location

Coastal Research Associates, Inc.

South Weymouth, Massachusetts, 02190, United States

Location

Bay State Clinical Trials, Inc.

Watertown, Massachusetts, 02472, United States

Location

Aa Mrc Llc

Flint, Michigan, 48503, United States

Location

Beyer Research

Kalamazoo, Michigan, 49009, United States

Location

The Center for Clinical Trials, Inc.

Biloxi, Mississippi, 39531, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, 63141, United States

Location

Digestive Health Associates

Reno, Nevada, 89511, United States

Location

Albuquerque Clinical Trials

Albuquerque, New Mexico, 87102, United States

Location

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, 87108, United States

Location

Drug Trials America

Hartsdale, New York, 10530, United States

Location

Manhattan Medical Research Practice PLLC

New York, New York, 10016, United States

Location

DiGiovanna Institute for Medical Education & Research

North Massapequa, New York, 11758-1802, United States

Location

UNC Health Care, University of North Carolina Medical Center, Memorial Hospital

Chapel Hill, North Carolina, 27514, United States

Location

PharmQuest

Greensboro, North Carolina, 27408, United States

Location

Northstate Clinical Research

Lenoir, North Carolina, 38645, United States

Location

Digestive Health Specialists, PA

Winston-Salem, North Carolina, 27103, United States

Location

New Horizons Clinical Research

Cincinnati, Ohio, 45242, United States

Location

Clinical Inquest Center LTD

Dayton, Ohio, 45419, United States

Location

Dayton Gastroenterology, Inc.

Dayton, Ohio, 45440, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, 19046, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Preferred Primary Care Physicians, INC

Pittsburgh, Pennsylvania, 15236, United States

Location

Montgomery Medical, Inc.

Smithfield, Pennsylvania, 15478, United States

Location

Partners In Clinical Research

Cumberland, Rhode Island, 02864, United States

Location

Greenville Pharmaceutical Research, Inc.

Greenville, South Carolina, 29615, United States

Location

Radiant Research, Inc.

Greer, South Carolina, 29651, United States

Location

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, 38119, United States

Location

Houston Endoscopy & Research Center

Houston, Texas, 77079, United States

Location

Research Across America

Plano, Texas, 75093, United States

Location

Sun Research Institute

San Antonio, Texas, 78125, United States

Location

Charlottesville Medical Research Center, LLC

Charlottesville, Virginia, 22911, United States

Location

MeSH Terms

Interventions

linaclotide

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Wieslaw Bochenek

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 29, 2015
• Study Start: November 1, 2015
• Primary Completion: February 5, 2018
• Study Completion: February 5, 2018
• Last Updated: August 22, 2019
• Results First Posted: August 22, 2019

Record last verified: 2019-08

Locations

US (79)