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)

NCT ID: NCT02559570

Last Updated: 2019-06-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-03

Study Completion Date

2018-05-29

Brief Summary

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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.

Detailed Description

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Conditions

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Functional Constipation in Children Ages 6-17 Years

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Participants aged 6 to 11 or 12 to 17 years received matching placebo linaclotide (LIN), 30 minutes before evening meal, once daily for 4 weeks. Administered as liquid oral solution for participants 6 to 11 years of age and solid oral capsule or liquid oral solution for participants 12 to 17 years of age.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants received matching placebo LIN liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

LIN Dose A (9 ug or 18 ug)

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 9 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 18 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Group Type EXPERIMENTAL

LIN Dose A

Intervention Type DRUG

Participants received LIN 9 or 18 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

LIN Dose B (18 ug or 36 ug)

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 18 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 36 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Group Type EXPERIMENTAL

LIN Dose B

Intervention Type DRUG

Participants received LIN 18 or 36 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

LIN Dose C (36 ug or 72 ug)

Participants aged 6 to 11 years with weight 18 to \<35 kg received LIN 36 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 6 to 11 years with weight ≥35 kg received LIN 72 ug, oral solution, 30 minutes before evening meal, once daily for 4 weeks. Participants aged 12 to 17 years received LIN 72 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Group Type EXPERIMENTAL

LIN Dose C

Intervention Type DRUG

Participants received LIN 36 or 72 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

LIN 145 µg

Participants aged 12 to 17 years received LIN 145 ug, oral solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Group Type EXPERIMENTAL

LIN 145 µg

Intervention Type DRUG

Participants received LIN 145 µg, liquid solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Interventions

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Placebo

Participants received matching placebo LIN liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

Intervention Type DRUG

LIN Dose A

Participants received LIN 9 or 18 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

Intervention Type DRUG

LIN Dose B

Participants received LIN 18 or 36 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

Intervention Type DRUG

LIN Dose C

Participants received LIN 36 or 72 ug liquid solution or solid capsules, orally, 30 minutes before evening meal, once daily for 4 weeks.

Intervention Type DRUG

LIN 145 µg

Participants received LIN 145 µg, liquid solution or solid capsules, 30 minutes before evening meal, once daily for 4 weeks.

Intervention Type DRUG

Other Intervention Names

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LINZESS LINZESS LINZESS LINZESS

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ironwood Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Forest Laboratories

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Taryn Weissman

Role: STUDY_DIRECTOR

Allergan, LLC

Locations

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HealthStar Research, LLC

Hot Springs, Arkansas, United States

Site Status

Applied Research Center of Arkansas

Little Rock, Arkansas, United States

Site Status

Advanced Research Center

Anaheim, California, United States

Site Status

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, United States

Site Status

WCCT Global, LLC

Costa Mesa, California, United States

Site Status

Ark Clinical Research

Long Beach, California, United States

Site Status

ACTCA, Inc

Los Angeles, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Orange County Research Institute

Ontario, California, United States

Site Status

Center for Clinical Trials, LLC

Paramount, California, United States

Site Status

UCSD Rady Children's Hospital

San Diego, California, United States

Site Status

University of California at San Francisco

San Francisco, California, United States

Site Status

Ventura Clinical Trials

Ventura, California, United States

Site Status

Colorado Springs Health Partners, HCP-Clinical Research, LLC

Colorado Springs, Colorado, United States

Site Status

Nova Southeastern University

Fort Lauderdale, Florida, United States

Site Status

Homestead Research Institute

Homestead, Florida, United States

Site Status

RM Medical Research

Homestead, Florida, United States

Site Status

Advanced Medical Research Center

Miami, Florida, United States

Site Status

SCORE Physician Alliance, LLC

St. Petersburg, Florida, United States

Site Status

Children's Center for Digestive Health Care LLC

Atlanta, Georgia, United States

Site Status

Sleepcare Clinical Research Institute

Stockbridge, Georgia, United States

Site Status

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, United States

Site Status

Heartland Research Associates, LLC

Wichita, Kansas, United States

Site Status

Kentucky Pediatric/ Adult Research

Bardstown, Kentucky, United States

Site Status

Kosair Children's Hospital - Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Site Status

Michael W. Simon, MD, PSC

Nicholasville, Kentucky, United States

Site Status

Willis-Knighton Physician Network

Shreveport, Louisiana, United States

Site Status

University of Maryland Children's Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University Of Minnesota

Minneapolis, Minnesota, United States

Site Status

GI Associates and Endoscopy Center

Jackson, Mississippi, United States

Site Status

Craig A. Speigel, MD

Bridgeton, Missouri, United States

Site Status

Midwest Children Health Research Institute

Lincoln, Nebraska, United States

Site Status

Midwest Children Health Research Institute

Lincoln, Nebraska, United States

Site Status

Goryeb Children's Hospital

Morristown, New Jersey, United States

Site Status

Columbia University Medical Center and Morgan Stanley

New York, New York, United States

Site Status

Asheboro Research Associates

Asheboro, North Carolina, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Capital Pediatrics and Adolescent Center PLLC

Raleigh, North Carolina, United States

Site Status

Ohio Pediatric Research Association

Dayton, Ohio, United States

Site Status

IPS Research Company

Oklahoma City, Oklahoma, United States

Site Status

Pediatric Care Specialists

Johnstown, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Preferred Primary Care Physicians, Inc.

Pittsburgh, Pennsylvania, United States

Site Status

Frontier Clinical Research, LLC

Scottdale, Pennsylvania, United States

Site Status

Montgomery Medical Inc.

Smithfield, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Coastal Pediatric Research

Charleston, South Carolina, United States

Site Status

Coastal Pediatrics Associates

Mt. Pleasant, South Carolina, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Texas Children's Hospital/Baylor College Medicine

Houston, Texas, United States

Site Status

Houston Clinical Research Associates

Houston, Texas, United States

Site Status

Sun Research Institute

San Antonio, Texas, United States

Site Status

Southwest Children's Research Associates, P.A.

San Antonio, Texas, United States

Site Status

ClinPoint Trials

Waxahachie, Texas, United States

Site Status

Foothill Family Clinic South / J. Lewis Research, Inc.

Salt Lake City, Utah, United States

Site Status

Pediatric Specialists of Virginia

Fairfax, Virginia, United States

Site Status

Virginia Tech Carilion School of Medicine Pediatric

Roanoke, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Stollery Children's Hospital

Edmonton, Alberta, Canada

Site Status

Children's Hospital of Western Ontario

London, Ontario, Canada

Site Status

Countries

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United States Canada

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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LIN-MD-62

Identifier Type: -

Identifier Source: org_study_id

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