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 (LIN-MD-63)

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome With Constipation	Drug: Linaclotide Dose A; Drug: Linaclotide Dose B; Drug: Linaclotide Dose C; Drug: Linaclotide Approved Adult Dose; Drug: Matching Placebo	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	260 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children, Ages 6 to 17 Years, A Multicenter, Randomized, Double-blind, Placebo-controlled Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 7-17 Years, With Irritable Bowel Syndrome With Constipation (IBS-C) (ie, Fulfill Rome III Criteria for Child/Adolescent IBS and Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation
Actual Study Start Date :	November 1, 2015
Estimated Primary Completion Date :	October 18, 2020
Estimated Study Completion Date :	October 18, 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Linaclotide Dose A; Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast. Dose A: 18 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg Dose A: 36 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg Dose A: 36 micrograms solid oral capsule in children 12-17 years of age	Drug: Linaclotide Dose A; Other Name: Linzess
Experimental: Linaclotide Dose B; Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast. Dose B: 36 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg Dose B: 72 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg Dose B: 72 micrograms solid oral capsule in children 12-17 years of age	Drug: Linaclotide Dose B; Other Name: Linzess
Experimental: Linaclotide Dose C; Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast. Dose C: 72 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight 18 to <35 kg Dose C: 145 micrograms liquid oral solution or solid oral capsule in children 7-11 years of age with weight ≥ 35 kg Dose C: 145 micrograms solid oral capsule in children 12-17 years of age	Drug: Linaclotide Dose C; Other Name: Linzess
Experimental: Linaclotide Approved Adult Dose; Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast. Approved Adult Dose: 290 micrograms solid oral capsule in children 12-17 years of age	Drug: Linaclotide Approved Adult Dose; Other Name: Linzess
Placebo Comparator: Matching Placebo; Taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center, after at least a 2-hour fast Placebo liquid oral solution or placebo solid oral capsule in children 7-11 years of age Placebo solid oral capsule in children 12-17 years of age	Drug: Matching Placebo; Other Name: Linzess

Outcome Measures

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Primary Outcome Measures :

1. Change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate (SBMs/week) during the Treatment Period [ Time Frame: Baseline to week 4 ]
   The numerator of the SBM rate (SBMs/week) during the Treatment Period will be derived based on the total number of SBMs a patient reported during the treatment period

Secondary Outcome Measures :

1. Change from baseline in 4-week abdominal pain daytime symptoms based on evening assessment of abdominal pain symptoms [ Time Frame: Baseline to week 4 ]
   Patients are asked to rate their abdominal pain from the time the patient wakes up until bedtime as part of the evening assessment. A 5-point rating scale is derived from the patient's responses, with 0 being no abdominal pain and 4 being a lot of abdominal pain.
2. Change from baseline in 4-week stool consistency [ Time Frame: Baseline to week 4 ]
   Patients will use the modified Pediatric Bristol Stool Form Scale (p-BSFS) to rate their stool consistency on a 7-point ordinal scale from 1 (hard lumps) to 7 (watery stool).
3. Change from baseline in 4-week severity of straining [ Time Frame: Baseline to week 4 ]
   Patients will assess the degree of staining on an ordinal scale from 0 (not at all) to 4 (very hard).
4. Change from baseline in 4-week abdominal bloating daytime symptoms based on evening assessment [ Time Frame: Baseline to week 4 ]
   Patients are asked to rate their abdominal bloating from the time the patient wakes up until bedtime as part of the evening assessment, and a 5-point rating scale is derived from the patient's responses, with 0 being no abdominal bloating and 4 being a lot of abdominal bloating.
5. Change from baseline in 4-week overall complete spontaneous bowel movement (CSBM) frequency rate (CSBMs per Week) [ Time Frame: Baseline to week 4 ]
   A patient's 4-week overall CSBM frequency rate will be the CSBM rate (CSBMs/week) calculated over the 4-week Treatment Period. The numerator of the CSBM rate (CSBMs/week) during the 4-week Treatment Period will be derived based on the total number of CSBMs a patient reported during the treatment period.

Eligibility Criteria

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Ages Eligible for Study:	7 Years to 17 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Contacts

Contact: Clincial Trials Registry Team	877-277-8566	IR-CTRegistration@allergan.com

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Sponsors and Collaborators

Forest Laboratories

Ironwood Pharmaceuticals, Inc.

Investigators

Study Chair:	Anna Muslin	Forest Laboratories, LLC, an Allergan Affiliate

More Information

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Responsible Party:	Forest Laboratories
ClinicalTrials.gov Identifier:	NCT02559817 History of Changes
Other Study ID Numbers:	LIN-MD-63
First Posted:	September 24, 2015
Last Update Posted:	June 12, 2018
Last Verified:	June 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Forest Laboratories:

Irritable Bowel Syndrome with Constipation in children; Linzess

Additional relevant MeSH terms:

Syndrome; Constipation; Irritable Bowel Syndrome; Disease; Pathologic Processes; Signs and Symptoms, Digestive	Signs and Symptoms; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases