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.
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.
Brief Title
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
Categories
Completion Date
Completion Date Type
Actual
Conditions
Irritable Bowel Syndrome With Constipation
Eligibility 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Irritable Bowel Syndrome with Constipation in children
Linzess
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
17 Years
Minimum Age
7 Years
NCT Id
NCT02559817
Org Class
Industry
Org Full Name
Forest Laboratories
Org Study Id
LIN-MD-63
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. SBM rate was defined as SBMs/week during the 4-week Treatment period. Participants recorded the occurrence of BMs and use of rescue medication, morning and evening, daily in an eDiary since pretreatment period. The SBM frequency rate (SBMs/week) during the analysis period for each participant were calculated as \[(total number of SBMs in the analysis period/number of days in the analysis period)\*7\]. Baseline value was based on values collected 14 days before randomization up to randomization. Change from Baseline was calculated as the SBM frequency rate during the 4-week treatment period - SBM frequency rate at baseline. A positive change from Baseline indicates improvement.
Outcome Measure
Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period
Outcome Time Frame
Baseline (14 days prior to randomization and up to randomization) to week 4
Secondary Outcomes
Outcome Description
The abdominal pain score was measured using 5-point scale. Participants answered the questions, How much did your tummy hurt as: 0=none, 1=a tiny bit, 2=a little, 3=some, and 4=a lot. The 4-week daytime abdominal pain was calculated as the average of nonmissing scores in evening eDiary during the Treatment Period with higher value indicating greater symptom severity. Baseline value was the average of non-missing values collected 14 days before randomization. Change from Baseline was calculated as the daytime abdominal pain score during the 4-week treatment period (i.e. average of non-missing daytime scores during 4-week treatment period) - daytime abdominal pain score at baseline. A negative change from Baseline indicates improvement.
Outcome Time Frame
Baseline (14 days prior to randomization) to week 4
Outcome Measure
Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms
Outcome Description
Participants used 7-point pediatric Bristol Stool Form (p-BSFS) scale to rate stool consistency for each BM in morning and evening eDiary where 1=small hard lumps or balls like pebbles,2=fat sausage shape but lumpy and hard,3=a sausage but with cracks on it,4=sausage or snake, smooth and soft,5=chicken nuggets, soft smooth blobs,6=oatmeal, fluffy mushy pieces,7=milkshake, watery. Scores in 4-week treatment period were calculated as mean of participants non-missing, SBM associated p-BSFS scores during 4-week treatment period. Baseline value was based on values collected 14 days before randomization up to randomization.
Outcome Time Frame
Baseline (14 days prior to randomization and up to randomization) to week 4
Outcome Measure
Change From Baseline in 4-week Stool Consistency
Outcome Description
Severity of straining was scored on 5-point scale for question-When you pooped, how hard did you push? The score ranges from 0= not hard at all,1= I pushed a tiny bit hard,2= I pushed a little hard,3= I pushed hard,4= I pushed very hard with higher scores indicating more severe straining. Participants recorded degree of straining for each BM in morning and evening eDiary. Scores during 4-week treatment period were calculated as mean of participant's non-missing, SBM associated straining scores during 4-week treatment period.
Outcome Time Frame
Baseline (14 days prior to randomization and up to randomization) to week 4
Outcome Measure
Change From Baseline in 4-week Severity of Straining
Outcome Description
Participants recorded their assessment of abdominal bloating in the evening eDiary. Participants answered the question: How big and full did your tummy feel? on a scale, where: 0=none, 1=a tiny bit, 2=a little, 3=medium or 4=very, with a higher score indicating more severe bloating. Baseline value was the average of values collected 14 days before randomization. The 4-week daytime abdominal bloating symptoms were calculated as the average of non-missing scores reported in the evening eDiary during the treatment period. Change from Baseline was calculated as the 4-week daytime abdominal bloating score during the treatment period - daytime abdominal bloating score at baseline. A negative change from Baseline indicates improvement.
Outcome Time Frame
Baseline (14 days prior to randomization) to week 4
Outcome Measure
Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment
Outcome Description
SBM was defined as a BM that occurred in the absence of laxative, suppository, or enema use on the calendar day of the BM or the calendar day before the BM. A CSBM was an SBM that was associated with a sense of complete evacuation. Participants recorded their assessment of the sensation of incomplete evacuation for each BM in the morning and evening eDiary. The 4-week overall CSBM frequency rate was calculated as \[total number of CSBMs in the analysis period/number of days in the analysis period\]\*7). Baseline value was based on values collected 14 days before randomization and up to randomization. Change from Baseline was calculated as the CSBM frequency rate during the 4-week treatment period - CSBM frequency rate at baseline. A positive change from Baseline indicates improvement.
Outcome Time Frame
Baseline (14 days prior to randomization and up to randomization) to week 4
Outcome Measure
Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Maximum Age Number (converted to Years and rounded down)
17
Minimum Age Number (converted to Years and rounded down)
7
Investigators
Investigator Type
Principal Investigator
Investigator Name
John Thompson
Investigator Email
JOTHOMPS@montefiore.org
Investigator Phone