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)

Forest Laboratories

Status and phase: Completed; Phase 2

Conditions: Functional Constipation in Children Ages 6-17 Years

Treatments: Drug: LIN 145 µg; Drug: LIN Dose C; Drug: LIN Dose B; Drug: Placebo; Drug: LIN Dose A

Study type: Interventional

Funder types: Industry

Identifiers

NCT02559570

LIN-MD-62

Details and patient eligibility

About

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.

Enrollment: 173 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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173 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age.

Treatment:

Drug: Placebo

LIN Dose A (9 ug or 18 ug)

Experimental group

Description:

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Treatment:

Drug: LIN Dose A

LIN Dose B (18 ug or 36 ug)

Experimental group

Description:

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Treatment:

Drug: LIN Dose B

LIN Dose C (36 ug or 72 ug)

Experimental group

Description:

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Treatment:

Drug: LIN Dose C

LIN 145 µg

Experimental group

Description:

Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Treatment:

Drug: LIN 145 µg