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
Condition: Irritable Bowel Syndrome With Constipation; Chronic Idiopathic Constipation
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Intervention: Linaclotide
Intervention description: Linaclotide capsules, orally, once daily.
Intervention MeSH terms: Linaclotide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 828.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunogenicity; Irritable Bowel Syndrome with Constipation; Chronic Idiopathic Constipation; Linaclotide; Linzess

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:

          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.