Clinical trial NCT02590432: 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
Official title: An Open-label, Long-term Study to Assess the Immunogenicity of Linaclotide Administered Orally to Adult Patients With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Irritable Bowel Syndrome With Constipation
Chronic Idiopathic Constipation
Keywords: Immunogenicity
Irritable Bowel Syndrome with Constipation
Chronic Idiopathic Constipation
Linaclotide
Linzess
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2015-10-29
Enrollment: 828
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This study includes up to a 3-week Screening Period, followed by a 52-week treatment period. Participants with CIC meeting the entry criteria received linaclotide 145 μg capsules, orally, once daily and participants with IBS-C meeting the entry criteria received linaclotide 290 μg capsules, orally, once daily. Participants with intolerable Adverse Events (AEs), following resolution of the AEs, could be randomized to receive 290 μg, 145 μg, or the lower dose of 72 μg linaclotide oral capsules for IBS-C; and 145 μg or 72 μg for CIC. Participants who experienced further intolerable AEs after the randomization could be transitioned to open-label 72 μg 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:

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.

Primary outcomes:
measure: Number of Participants With Positive Treatment-Related Anti-Drug Antibodies (ADA) in Serum
timeFrame: Baseline (Day 1) up to 52 weeks or 8 months post last dose if ADA positive at Week 52 (approximately 84 weeks)
Secondary outcomes:
measure: Change From Baseline in Participant's Assessment of Constipation Severity
timeFrame: Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)
measure: Change From Baseline in Participant Assessment of Irritable Bowel Syndrome (IBS) Symptom Severity for Participants With Irritable Bowel Syndrome With Constipation (IBS-C)
timeFrame: Baseline (Day 1) to Week 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)
measure: Change From Baseline in Degree of Relief of IBS Symptoms for Participants With IBS-C
timeFrame: Baseline (Day 1) to Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)
measure: IBS Treatment Satisfaction Assessment Postbaseline for Participants With IBS-C
timeFrame: Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)
measure: Constipation Treatment Satisfaction Assessment Postbaseline for Participants With Chronic Idiopathic Constipation (CIC)
timeFrame: Weeks 2, 4, 12, 26, 40 and 52 (Open Label Treatment Period)
measure: Number of Participants With Recurrence of Diarrhea
timeFrame: From first dose in the Double-blind Treatment Period to Week 52
measure: Number of Participants With Recurrence of Intolerable Diarrhea
timeFrame: From first dose in the Double-blind Treatment Period to Week 52
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAE)
timeFrame: From first dose of study treatment up to Week 52
measure: Time to First Recurrence of Diarrhea
timeFrame: From first dose in the Double-blind Treatment Period to Week 52
measure: Time to First Recurrence of Intolerable Diarrhea
timeFrame: From first dose in the Double-blind Treatment Period to Week 52
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Athens
country: United States
facility: North Alabama Research Center, LLC
state: Alabama
city: Childersburg
country: United States
facility: Alliance Clinical Research
state: Alabama
city: Foley
country: United States
facility: G & L Research, LLC
state: Alabama
city: Chandler
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Scottsdale
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Surprise
country: United States
facility: Clinical Research Institute of Arizona, LLC
state: Arizona
city: Tempe
country: United States
facility: Clinical Research Consortium
state: Arizona
city: Tucson
country: United States
facility: Desert Sun Clinical Research, LLC.
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners, Inc.
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas
state: Arkansas
city: Corona
country: United States
facility: Kindred Medical Institute for Clinical Trials, LLC
state: California
city: Costa Mesa
country: United States
facility: Global Clinical Trials LLC
state: California
city: Encinitas
country: United States
facility: Diagnamics Inc
state: California
city: Fountain Valley
country: United States
facility: MD Studies, Inc.
state: California
city: Fresno
country: United States
facility: Research Center of Fresno, Inc.
state: California
city: Garden Grove
country: United States
facility: VVCRD Clinical Research
state: California
city: Mission Hills
country: United States
facility: Facey Medical Foundation
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: Precision Research Institute
state: California
city: Upland
country: United States
facility: Empire Clinical Research
state: California
city: Denver
country: United States
facility: Lynn Institute of Denver
state: Colorado
city: Boynton Beach
country: United States
facility: ZASA Clinical Research
state: Florida
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Brandon
country: United States
facility: Clinical Research of Brandon LLC
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Hialeah
country: United States
facility: Direct Helpers Research Center
state: Florida
city: Hialeah
country: United States
facility: Eastern Research, Inc.
state: Florida
city: Maitland
country: United States
facility: Center for Advanced Gastroenterology
state: Florida
city: Miami
country: United States
facility: Florida Medical Center and Research, Inc.
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Port Orange
country: United States
facility: Accord Clinical Research
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Blue Ridge
country: United States
facility: River Birch Research Alliance, LLC
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Rockford
country: United States
facility: Rockford Gastroenterology Associates
state: Illinois
city: Clive
country: United States
facility: Iowa Digestive Center, PC
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: West Des Moines
country: United States
facility: Integrated Clinical Trial Services, Inc.
state: Iowa
city: Newton
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Pratt
country: United States
facility: Health Science Research Center
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Natchitoches
country: United States
facility: KAMP Medical Research Inc
state: Louisiana
city: South Weymouth
country: United States
facility: Coastal Research Associates, Inc.
state: Massachusetts
city: Watertown
country: United States
facility: Bay State Clinical Trials, Inc.
state: Massachusetts
city: Flint
country: United States
facility: Aa Mrc Llc
state: Michigan
city: Kalamazoo
country: United States
facility: Beyer Research
state: Michigan
city: Biloxi
country: United States
facility: The Center for Clinical Trials, Inc.
state: Mississippi
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Reno
country: United States
facility: Digestive Health Associates
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources, Inc.
state: New Mexico
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: New York
country: United States
facility: Manhattan Medical Research Practice PLLC
state: New York
city: North Massapequa
country: United States
facility: DiGiovanna Institute for Medical Education & Research
state: New York
city: Chapel Hill
country: United States
facility: UNC Health Care, University of North Carolina Medical Center, Memorial Hospital
state: North Carolina
city: Greensboro
country: United States
facility: PharmQuest
state: North Carolina
city: Lenoir
country: United States
facility: Northstate Clinical Research
state: North Carolina
city: Winston-Salem
country: United States
facility: Digestive Health Specialists, PA
state: North Carolina
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Dayton
country: United States
facility: Clinical Inquest Center LTD
state: Ohio
city: Dayton
country: United States
facility: Dayton Gastroenterology, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, INC
state: Pennsylvania
city: Smithfield
country: United States
facility: Montgomery Medical, Inc.
state: Pennsylvania
city: Cumberland
country: United States
facility: Partners In Clinical Research
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc.
state: South Carolina
city: Greer
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Houston
country: United States
facility: Houston Endoscopy & Research Center
state: Texas
city: Plano
country: United States
facility: Research Across America
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC
state: Virginia
Study officials:
affiliation: Allergan
name: Wieslaw Bochenek
role: STUDY_DIRECTOR
References: