Clinical trial NCT02559570: A Safety and Efficacy Study of a Range of Linaclotide Doses Administered Orally to Children Ages 6-17 Years Who Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation (FC)
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, Who Fulfill Modified Rome III Criteria for Child/Adolescent Functional Constipation (FC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Functional Constipation in Children Ages 6-17 Years
Keywords: Functional constipation in children
LINZESS
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2015-09-24
Enrollment: 173
Sex: ALL
Minimum age (years): 6
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 was to evaluate dose response of the safety and efficacy of linaclotide for the treatment of functional constipation (FC), in children age 6-17 years. This study includes up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Participants age 6-11 years will receive oral liquid formulation and participants 12-17 years will receive solid oral capsule or liquid oral solution.

Children ages 6-11 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 FC.


Eligibility criteria: Inclusion Criteria:

* Participant weighs at least 18 kg (kilograms) (39.7 lbs)
* Participant meets modified Rome III criteria for child/adolescent FC: For at least 2 months before the Screening Visit, the participant 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 faecal mass in the rectum
* d) History of large diameter stools that may obstruct the toilet
* e) At least one episode of fecal incontinence per week
* Participant is willing to discontinue any laxatives used before the Pretreatment Visit in favor of the protocol-permitted rescue medicine
* Participant 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
* Participant or participant/guardian/legally authorized representative (LAR) or caregiver is compliant with electronic diary (eDiary) by completing both the morning and evening assessments for 10 out of the 14 days immediately preceding the Randomization Visit

Exclusion Criteria:

* Participant meets Rome III criteria for Child/Adolescent irritable bowel syndrome (IBS): At least once per week for at least 2 months before the Screening Visit, the participant has 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:
* 1. Improvement with defecation
* 2. Onset associated with a change in frequency of stool
* 3. Onset associated with a change in form (appearance) of stool
* Participant 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
* Participant has required manual or hospital-based disimpassion any time prior to randomization
* Participant is unable to tolerate the placebo during the Screening Period

Primary outcomes:
measure: Change From Baseline (CFB) in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate During the Treatment Period
timeFrame: Baseline (14-day prior to randomization and up to randomization) to Week 4
Secondary outcomes:
measure: Change From Baseline (CFB) in 4-week Daytime Abdominal Pain
timeFrame: Baseline (14-day prior to randomization) to Week 4
measure: Change From Baseline (CFB) in 4-week Stool Consistency
timeFrame: Baseline (14-day prior to randomization and up to randomization) to Week 4
measure: Change From Baseline (CFB) in 4-week of Severity of Straining
timeFrame: Baseline (14-day prior to randomization and up to randomization) to Week 4
measure: Change From Baseline (CFB) in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment
timeFrame: Baseline (14-day prior to randomization) to Week 4
measure: Change From Baseline (CFB) in 4-week Overall Complete Spontaneous Bowel Movement Frequency Rate (CSBM/Week) During the Treatment Period
timeFrame: Baseline (14-day prior to randomization and up to randomization) to Week 4
measure: Change From Baseline in 4-week Fecal Incontinence Daytime Symptoms Based on Evening Assessment
timeFrame: Baseline (14-day prior 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
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: Long Beach
country: United States
facility: Ark Clinical Research
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: Ontario
country: United States
facility: Orange County Research Institute
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC
state: California
city: San Diego
country: United States
facility: UCSD Rady Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: Colorado Springs Health Partners, HCP-Clinical Research, LLC
state: Colorado
city: Fort Lauderdale
country: United States
facility: Nova Southeastern University
state: Florida
city: Homestead
country: United States
facility: Homestead Research Institute
state: Florida
city: Homestead
country: United States
facility: RM Medical Research
state: Florida
city: Miami
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Saint Petersburg
country: United States
facility: SCORE Physician Alliance, LLC
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: 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: Bardstown
country: United States
facility: Kentucky Pediatric/ Adult Research
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital - Pediatric Clinical Research Unit
state: Kentucky
city: Nicholasville
country: United States
facility: Michael W. Simon, MD, PSC
state: Kentucky
city: Shreveport
country: United States
facility: Willis-Knighton Physician Network
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Children's Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University Of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: GI Associates and Endoscopy Center
state: Mississippi
city: Bridgeton
country: United States
facility: Craig A. Speigel, MD
state: Missouri
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
state: New York
city: Asheboro
country: United States
facility: Asheboro Research Associates
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Capital Pediatrics and Adolescent Center PLLC
state: North Carolina
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: Johnstown
country: United States
facility: Pediatric Care Specialists
state: Pennsylvania
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: San Antonio
country: United States
facility: Southwest Children's Research Associates, P.A.
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials
state: Texas
city: Salt Lake City
country: United States
facility: Foothill Family Clinic South / J. Lewis Research, Inc.
state: Utah
city: Fairfax
country: United States
facility: Pediatric Specialists of Virginia
state: Virginia
city: Roanoke
country: United States
facility: Virginia Tech Carilion School of Medicine Pediatric
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: London
country: Canada
facility: Children's Hospital of Western Ontario
state: Ontario
Study officials:
affiliation: Allergan, LLC
name: Taryn Weissman
role: STUDY_DIRECTOR
References: