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
- Conditions
- Irritable Bowel Syndrome With Constipation
- Interventions
- Registration Number
- NCT02559817
- Lead Sponsor
- Forest Laboratories
- 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 available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 101
- 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Linaclotide Approved Adult Dose 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 Linaclotide Dose A 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 Linaclotide Dose C 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 Matching Placebo 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 Linaclotide Dose B 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
- Primary Outcome Measures
Name Time Method Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period Baseline (14 days prior to randomization and up to randomization) to week 4 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms Baseline (14 days prior to randomization) to week 4 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.
Change From Baseline in 4-week Stool Consistency Baseline (14 days prior to randomization and up to randomization) to week 4 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.
Change From Baseline in 4-week Severity of Straining Baseline (14 days prior to randomization and up to randomization) to week 4 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.
Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment Baseline (14 days prior to randomization) to week 4 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.
Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week) Baseline (14 days prior to randomization and up to randomization) to week 4 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.
Trial Locations
- Locations (47)
Advanced Research Center - Site 069
🇺🇸Anaheim, California, United States
Midwest Children Health Research Institute
🇺🇸Lincoln, Nebraska, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Center for Digestive Health Care LLC
🇺🇸Atlanta, Georgia, United States
Preferred Primary Care Physicians, Inc.
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Children's Hospital/Baylor College Medicine
🇺🇸Houston, Texas, United States
Houston Clinical Research Associates
🇺🇸Houston, Texas, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
HealthStar Research, LLC
🇺🇸Hot Springs, Arkansas, United States
GI Associates and Endoscopy Center
🇺🇸Jackson, Mississippi, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Columbia University Medical Center and Morgan Stanley Children's Hospital of New York
🇺🇸New York, New York, United States
Advanced Medical Research Center
🇺🇸Miami, Florida, United States
Certified Research Consultants Virgo/Carter Pediatrics
🇺🇸Silver Spring, Maryland, United States
Boys Town National Research Hospital
🇺🇸Boys Town, Nebraska, United States
Capital Pediatrics and Adolescent Center PLLC
🇺🇸Raleigh, North Carolina, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
IPS Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Montgomery Medical Inc.
🇺🇸Smithfield, Pennsylvania, United States
Coastal Pediatrics Associates
🇺🇸Mount Pleasant, South Carolina, United States
ClinPoint Trials
🇺🇸Waxahachie, Texas, United States
Children's Hospital of Western Ontario
🇨🇦London, Ontario, Canada
Physician's Clinical Research Inc.
🇨🇦Vaughan, Ontario, Canada
Applied Research Center of Arkansas
🇺🇸Little Rock, Arkansas, United States
ACTCA, Inc
🇺🇸Los Angeles, California, United States
WCCT Global, LLC
🇺🇸Costa Mesa, California, United States
Kindred Medical Institute for Clinical Trials, LLC
🇺🇸Corona, California, United States
Center for Clinical Trials, LLC
🇺🇸Paramount, California, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
Sleepcare Clinical Research Institute
🇺🇸Stockbridge, Georgia, United States
Riley Hospital for Children at Indiana University Health
🇺🇸Indianapolis, Indiana, United States
Methodist Medical Center
🇺🇸Peoria, Illinois, United States
Heartland Research Associates, LLC
🇺🇸Wichita, Kansas, United States
Willis-Knighton Physician Network
🇺🇸Shreveport, Louisiana, United States
Goryeb Children's Hospital
🇺🇸Morristown, New Jersey, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Asheboro Research Associates - Site 022
🇺🇸Asheboro, North Carolina, United States
Ohio Pediatric Research Association
🇺🇸Dayton, Ohio, United States
Frontier Clinical Research, LLC
🇺🇸Scottdale, Pennsylvania, United States
Coastal Pediatric Research
🇺🇸Charleston, South Carolina, United States
Sun Research Institute
🇺🇸San Antonio, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Virginia Tech Carilion School of Medicine Pediatric Gastroenterology
🇺🇸Roanoke, Virginia, United States
Aurora Health Care, Aurora Medical Center in Summit
🇺🇸Summit, Wisconsin, United States
MultiCare Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States