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

Irritable Bowel Syndrome With Constipation Clinical Trial

— LIN-MD-63  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02559817
• Other study ID #: LIN-MD-63
• Status: Terminated
• Phase: Phase 2
• Start date: November 1, 2015
• Est. completion date: August 30, 2019

Study information

• Verified date: December 2020
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 101
• Est. completion date: August 30, 2019
• Est. primary completion date: August 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Constipation
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Constipation
• Syndrome

Intervention

Drug:
• Linaclotide Dose A

• Linaclotide Dose B

• Linaclotide Dose C

• Linaclotide Approved Adult Dose

• Matching Placebo

Locations

Country	Name	City	State
Canada	Children's Hospital of Western Ontario	London	Ontario
Canada	Physician's Clinical Research Inc.	Vaughan	Ontario
United States	Advanced Research Center - Site 069	Anaheim	California
United States	Asheboro Research Associates - Site 022	Asheboro	North Carolina
United States	Children's Center for Digestive Health Care LLC	Atlanta	Georgia
United States	Boys Town National Research Hospital	Boys Town	Nebraska
United States	Coastal Pediatric Research	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	WCCT Global, LLC	Costa Mesa	California
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	HealthStar Research, LLC	Hot Springs	Arkansas
United States	Houston Clinical Research Associates	Houston	Texas
United States	Texas Children's Hospital/Baylor College Medicine	Houston	Texas
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	GI Associates and Endoscopy Center	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Midwest Children Health Research Institute	Lincoln	Nebraska
United States	Midwest Children Health Research Institute	Lincoln	Nebraska
United States	Applied Research Center of Arkansas	Little Rock	Arkansas
United States	ACTCA, Inc	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Advanced Medical Research Center	Miami	Florida
United States	Goryeb Children's Hospital	Morristown	New Jersey
United States	Coastal Pediatrics Associates	Mount Pleasant	South Carolina
United States	Columbia University Medical Center and Morgan Stanley Children's Hospital of New York	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Center for Clinical Trials, LLC	Paramount	California
United States	Methodist Medical Center	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Preferred Primary Care Physicians, Inc.	Pittsburgh	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Capital Pediatrics and Adolescent Center PLLC	Raleigh	North Carolina
United States	Virginia Tech Carilion School of Medicine Pediatric Gastroenterology	Roanoke	Virginia
United States	Sun Research Institute	San Antonio	Texas
United States	University of California at San Francisco	San Francisco	California
United States	Frontier Clinical Research, LLC	Scottdale	Pennsylvania
United States	Willis-Knighton Physician Network	Shreveport	Louisiana
United States	Certified Research Consultants Virgo/Carter Pediatrics	Silver Spring	Maryland
United States	Montgomery Medical Inc.	Smithfield	Pennsylvania
United States	Sleepcare Clinical Research Institute	Stockbridge	Georgia
United States	Aurora Health Care, Aurora Medical Center in Summit	Summit	Wisconsin
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	ClinPoint Trials	Waxahachie	Texas
United States	Heartland Research Associates, LLC	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period	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.	Baseline (14 days prior to randomization and up to randomization) to week 4
Secondary	Change From Baseline in 4-week Abdominal Pain Daytime Symptoms Based on Evening Assessment of Abdominal Pain Symptoms	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.	Baseline (14 days prior to randomization) to week 4
Secondary	Change From Baseline in 4-week Stool Consistency	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.	Baseline (14 days prior to randomization and up to randomization) to week 4
Secondary	Change From Baseline in 4-week Severity of Straining	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.	Baseline (14 days prior to randomization and up to randomization) to week 4
Secondary	Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment	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.	Baseline (14 days prior to randomization) to week 4
Secondary	Change From Baseline in 4-week Overall Complete Spontaneous Bowel Movement (CSBM) Frequency Rate (CSBMs Per Week)	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.	Baseline (14 days prior to randomization and up to randomization) to week 4