A Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 6-17 Years Who Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation (FC)
Condition: Functional Constipation in Children Ages 6-17 Years
MeSH terms: Constipation
Intervention: Placebo; LIN Dose A; LIN Dose B; LIN Dose C; LIN 145 µg
Intervention description: Participants received matching placebo LIN liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.; Participants received LIN 9 or 18 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.; Participants received LIN 18 or 36 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.; Participants received LIN 36 or 72 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.; Participants received LIN 145 µg, liquid solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.
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: 173.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Functional constipation in children; LINZESS

Summary:

      The purpose of this study was to evaluate dose response of the safety and efficacy of
      linaclotide for the treatment of functional constipation (FC), in children age 6-17 years.
      This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period.
      Participants age 6-11 years will receive oral liquid formulation and participants 12-17 years
      will receive solid oral capsule or liquid oral solution.

      Children ages 6-11 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 FC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant weighs at least 18 kg (kilograms) (39.7 lbs)

          -  Participant meets modified Rome III criteria for child/adolescent FC: For at least 2
             months before the Screening Visit, the participant 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 faecal mass in the rectum

          -  d) History of large diameter stools that may obstruct the toilet

          -  e) At least one episode of fecal incontinence per week

          -  Participant is willing to discontinue any laxatives used before the Pretreatment Visit
             in favor of the protocol-permitted rescue medicine

          -  Participant 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

          -  Participant or participant/guardian/legally authorized representative (LAR) or
             caregiver is compliant with electronic diary (eDiary) by completing both the morning
             and evening assessments for 10 out of the 14 days immediately preceding the
             Randomization Visit

        Exclusion Criteria:

          -  Participant meets Rome III criteria for Child/Adolescent irritable bowel syndrome
             (IBS): At least once per week for at least 2 months before the Screening Visit, the
             participant has 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:

          -  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

          -  Participant 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

          -  Participant has required manual or hospital-based disimpassion any time prior to
             randomization

          -  Participant is unable to tolerate the placebo during the Screening Period