A Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 7-17 Years, With Irritable Bowel Syndrome With Constipation
Condition: Irritable Bowel Syndrome With Constipation
MeSH terms: Irritable Bowel Syndrome; Syndrome; Constipation
Intervention: Linaclotide Dose A; Linaclotide Dose B; Linaclotide Dose C; Linaclotide Approved Adult Dose; Matching Placebo
Intervention MeSH terms: Linaclotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 101.0
Sex: All
Minimum age: 7 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Irritable Bowel Syndrome with Constipation in children; Linzess

Summary:

      The purpose of this study is to evaluate the safety and efficacy of linaclotide for the
      treatment of Irritable Bowel syndrome with Constipation (IBS-C), in children age 7-17 years.

      This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period.
      Patients age 7-11 will receive oral liquid or oral solid capsule and patients 12-17 will
      receive solid oral capsule formulation. Children ages 7-11 years meeting the entry criteria
      will be randomized to 1 of 3 doses of linaclotide or placebo for 4 weeks. Children ages 12-17
      years meeting the entry criteria will be randomized to 1 of 4 doses of linaclotide or placebo
      for 4 weeks.

      This 4-week study will assess the effects of linaclotide on bowel movement frequency, as well
      as other bowel symptoms of IBS-C.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient weighs at least 18 kg (39.7 lbs)

          -  Patient meets Rome III criteria for child/adolescent IBS: at least once per week for
             at least 2 months before Screening Visit, the patient experienced abdominal discomfort
             (an uncomfortable sensation not described as pain) or pain associated with 2 or more
             of the following at least 25% of the time:

          -  a) Improvement with defecation

          -  b) Onset associated with a change in frequency of stool

          -  c) Onset associated with a change in form (appearance) of stool

          -  Patient meets modified Rome III criteria for child/adolescent Functional Constipation
             (FC): For at least 2 months before the Screening Visit, the patient has had 2 or fewer
             defecations (with each defecation occurring in the absence of any laxative,
             suppository, or enema use during the preceding 24 hours) in the toilet per week. In
             addition, at least once per week, patient meets 1 or more of the following:

          -  a) History of retentive posturing or excessive volitional stool retention

          -  b) History of painful or hard bowel movements (BMs)

          -  c) Presence of a large fecal mass in the rectum

          -  d) History of large diameter stools that may obstruct the toilet

          -  Patient is willing to discontinue any laxatives used before the Pretreatment Visit in
             favor of the protocol-permitted rescue medicine

          -  Patient has an average of fewer than 3 spontaneous BMs (SBMs) per week during the 14
             days before the randomization day and up to the randomization. An SBM is defined as a
             BM that occurs in the absence of laxative, enema, or suppository use on the calendar
             day of the BM or the calendar day before the BM

          -  Patient or parent/guardian/LAR or caregiver is compliant with eDiary by completing
             both the morning and evening assessments for 10 out of the 14 days immediately
             preceding the Randomization Visit

        Exclusion Criteria:

          -  Patient reports having more than 1 loose, mushy stool (eDiary-recorded stool
             consistency of 6 on the Pediatric Bristol Stool Form Scale [p-BSFS]) or any watery
             stool (eDiary-recorded stool consistency of 7 on the p-BSFS) with any SBM that
             occurred in the absence of laxative use on the calendar day of the BM or the calendar
             day before the BM during the 14 days before the randomization day and up to the
             randomization

          -  Select medical history or conditions that may be related to other causes of
             constipation or may interfere with safety and efficacy analyses

          -  Patient has required manual disimpaction anytime prior to randomization or
             disimpaction during in-patient hospitalization within one year prior to randomization

          -  Patient is unable to tolerate the placebo during rhe Screening Period