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)
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| ClinicalTrials.gov Identifier: NCT02559817 |
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Recruitment Status :
Terminated
First Posted : September 24, 2015
Last Update Posted : September 16, 2019
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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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 101 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 |
| Actual Primary Completion Date : | August 30, 2019 |
| Actual Study Completion Date : | August 30, 2019 |
| Arm | Intervention/treatment |
|---|---|
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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 |
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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 |
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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 |
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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 |
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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 |
- 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
- 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.
- 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).
- 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).
- 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.
- 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.
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| Ages Eligible for Study: | 7 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02559817
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| Study Chair: | Anna Muslin | Forest Laboratories, LLC, an Allergan Affiliate |
| Responsible Party: | Forest Laboratories |
| ClinicalTrials.gov Identifier: | NCT02559817 |
| Other Study ID Numbers: |
LIN-MD-63 |
| First Posted: | September 24, 2015 Key Record Dates |
| Last Update Posted: | September 16, 2019 |
| Last Verified: | September 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Irritable Bowel Syndrome with Constipation in children Linzess |
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Irritable Bowel Syndrome Syndrome Constipation Disease Pathologic Processes Signs and Symptoms, Digestive Signs and Symptoms Colonic Diseases, Functional Colonic Diseases |
Intestinal Diseases Gastrointestinal Diseases Digestive System Diseases Linaclotide Guanylyl Cyclase C Agonists Enzyme Activators Molecular Mechanisms of Pharmacological Action Gastrointestinal Agents |