Clinical trial NCT02559817: 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: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome With Constipation
Keywords: Irritable Bowel Syndrome with Constipation in children
Linzess
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2015-09-24
Enrollment: 101
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period
timeFrame: Baseline (14 days prior to randomization and up to randomization) to week 4
Secondary outcomes:
measure: Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms
timeFrame: Baseline (14 days prior to randomization) to week 4
measure: Change From Baseline in 4-week Stool Consistency
timeFrame: Baseline (14 days prior to randomization and up to randomization) to week 4
measure: Change From Baseline in 4-week Severity of Straining
timeFrame: Baseline (14 days prior to randomization and up to randomization) to week 4
measure: Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment
timeFrame: Baseline (14 days prior to randomization) to week 4
measure: Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)
timeFrame: Baseline (14 days prior to randomization and up to randomization) to week 4
Other outcomes:
Locations:
city: Hot Springs
country: United States
facility: HealthStar Research, LLC
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center - Site 069
state: California
city: Corona
country: United States
facility: Kindred Medical Institute for Clinical Trials, LLC
state: California
city: Costa Mesa
country: United States
facility: WCCT Global, LLC
state: California
city: Los Angeles
country: United States
facility: ACTCA, Inc
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Miami
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Atlanta
country: United States
facility: Children's Center for Digestive Health Care LLC
state: Georgia
city: Stockbridge
country: United States
facility: Sleepcare Clinical Research Institute
state: Georgia
city: Peoria
country: United States
facility: Methodist Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Wichita
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Shreveport
country: United States
facility: Willis-Knighton Physician Network
state: Louisiana
city: Silver Spring
country: United States
facility: Certified Research Consultants Virgo/Carter Pediatrics
state: Maryland
city: Jackson
country: United States
facility: GI Associates and Endoscopy Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Boys Town
country: United States
facility: Boys Town National Research Hospital
state: Nebraska
city: Lincoln
country: United States
facility: Midwest Children Health Research Institute
state: Nebraska
city: Lincoln
country: United States
facility: Midwest Children Health Research Institute
state: Nebraska
city: Morristown
country: United States
facility: Goryeb Children's Hospital
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center and Morgan Stanley Children's Hospital of New York
state: New York
city: Asheboro
country: United States
facility: Asheboro Research Associates - Site 022
state: North Carolina
city: Raleigh
country: United States
facility: Capital Pediatrics and Adolescent Center PLLC
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatric Research Association
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Preferred Primary Care Physicians, Inc.
state: Pennsylvania
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC
state: Pennsylvania
city: Smithfield
country: United States
facility: Montgomery Medical Inc.
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Coastal Pediatric Research
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Pediatrics Associates
state: South Carolina
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital/Baylor College Medicine
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Associates
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Roanoke
country: United States
facility: Virginia Tech Carilion School of Medicine Pediatric Gastroenterology
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Summit
country: United States
facility: Aurora Health Care, Aurora Medical Center in Summit
state: Wisconsin
city: London
country: Canada
facility: Children's Hospital of Western Ontario
state: Ontario
city: Vaughan
country: Canada
facility: Physician's Clinical Research Inc.
state: Ontario
Study officials:
affiliation: Forest Laboratories, LLC, an Allergan Affiliate
name: Anna Muslin
role: STUDY_CHAIR
References: