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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
Recruitment Status : Terminated
First Posted : September 24, 2015
Last Update Posted : September 16, 2019
Sponsor:
Collaborator:
Ironwood Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Forest Laboratories

Tracking Information
First Submitted Date  ICMJE September 23, 2015
First Posted Date  ICMJE September 24, 2015
Last Update Posted Date September 16, 2019
Actual Study Start Date  ICMJE November 1, 2015
Actual Primary Completion Date August 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
  • Change from baseline in 4-week abdominal pain daytime symptoms based on evening assessment of abdominal pain symptoms [ Time Frame: Baseline to week 4 ]
  • 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 asses 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 ]
  • Change from baseline in 4-week overall complete spontaneous bowel movement (CSBM) frequency rate (CSBMs per Week) [ Time Frame: Baseline to week 4 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Irritable Bowel Syndrome With Constipation
Intervention  ICMJE
  • Drug: Linaclotide Dose A
    Other Name: Linzess
  • Drug: Linaclotide Dose B
    Other Name: Linzess
  • Drug: Linaclotide Dose C
    Other Name: Linzess
  • Drug: Linaclotide Approved Adult Dose
    Other Name: Linzess
  • Drug: Matching Placebo
    Other Name: Linzess
Study Arms  ICMJE
  • 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

    Intervention: Drug: Linaclotide Dose A
  • 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

    Intervention: Drug: Linaclotide Dose B
  • 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

    Intervention: Drug: Linaclotide Dose C
  • 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

    Intervention: Drug: Linaclotide Approved Adult Dose
  • 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

    Intervention: Drug: Matching Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 12, 2019)
101
Original Estimated Enrollment  ICMJE
 (submitted: September 23, 2015)
260
Actual Study Completion Date  ICMJE August 30, 2019
Actual Primary Completion Date August 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02559817
Other Study ID Numbers  ICMJE LIN-MD-63
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Forest Laboratories
Study Sponsor  ICMJE Forest Laboratories
Collaborators  ICMJE Ironwood Pharmaceuticals, Inc.
Investigators  ICMJE
Study Chair: Anna Muslin Forest Laboratories, LLC, an Allergan Affiliate
PRS Account Forest Laboratories
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP