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

NCT02559817 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: LIN-MD-63
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 48

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.

Conditions

Irritable Bowel Syndrome With Constipation

Keywords

Irritable Bowel Syndrome with Constipation in children; Linzess

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• Change From Baseline in 4-week Stool Consistency

  Baseline (14 days prior to randomization and up to randomization) to week 4

• Change From Baseline in 4-week Severity of Straining

  Baseline (14 days prior to randomization and up to randomization) to week 4

• Change From Baseline in 4-week Abdominal Bloating Daytime Symptoms Based on Evening Assessment

  Baseline (14 days prior to randomization) to week 4

• 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

Study Arms (5)

Linaclotide Dose A

EXPERIMENTAL

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

Drug: Linaclotide Dose A

Linaclotide Dose B

EXPERIMENTAL

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

Drug: Linaclotide Dose B

Linaclotide Dose C

EXPERIMENTAL

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

Drug: Linaclotide Dose C

Linaclotide Approved Adult Dose

EXPERIMENTAL

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

Drug: Linaclotide Approved Adult Dose

Matching Placebo

PLACEBO COMPARATOR

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

Drug: Matching Placebo

Interventions

Linaclotide Dose A DRUG

Also known as: Linzess

Linaclotide Dose A

Linaclotide Dose B DRUG

Also known as: Linzess

Linaclotide Dose B

Linaclotide Dose C DRUG

Also known as: Linzess

Linaclotide Dose C

Linaclotide Approved Adult Dose DRUG

Also known as: Linzess

Linaclotide Approved Adult Dose

Matching Placebo DRUG

Also known as: Linzess

Matching Placebo

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Forest Laboratories: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (48)

HealthStar Research, LLC

Hot Springs, Arkansas, 71913, United States

Location

Applied Research Center of Arkansas

Little Rock, Arkansas, 72212, United States

Location

Advanced Research Center - Site 069

Anaheim, California, 92805, United States

Location

Kindred Medical Institute for Clinical Trials, LLC

Corona, California, 92879, United States

Location

WCCT Global, LLC

Costa Mesa, California, 92626, United States

Location

ACTCA, Inc

Los Angeles, California, 90017, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Center for Clinical Trials, LLC

Paramount, California, 90723, United States

Location

University of California at San Francisco

San Francisco, California, 94143, United States

Location

Advanced Medical Research Center

Miami, Florida, 33135, United States

Location

Children's Center for Digestive Health Care LLC

Atlanta, Georgia, 30342, United States

Location

Sleepcare Clinical Research Institute

Stockbridge, Georgia, 30281, United States

Location

Methodist Medical Center

Peoria, Illinois, 61602, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Heartland Research Associates, LLC

Wichita, Kansas, 67205, United States

Location

Willis-Knighton Physician Network

Shreveport, Louisiana, 71118, United States

Location

Certified Research Consultants Virgo/Carter Pediatrics

Silver Spring, Maryland, 20910, United States

Location

GI Associates and Endoscopy Center

Jackson, Mississippi, 39202, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Boys Town National Research Hospital

Boys Town, Nebraska, 68010, United States

Location

Midwest Children Health Research Institute

Lincoln, Nebraska, 68505, United States

Location

Midwest Children Health Research Institute

Lincoln, Nebraska, 68516, United States

Location

Goryeb Children's Hospital

Morristown, New Jersey, 07962, United States

Location

Columbia University Medical Center and Morgan Stanley Children's Hospital of New York

New York, New York, 10032, United States

Location

Asheboro Research Associates - Site 022

Asheboro, North Carolina, 27203, United States

Location

Capital Pediatrics and Adolescent Center PLLC

Raleigh, North Carolina, 27609, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Ohio Pediatric Research Association

Dayton, Ohio, 45414, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Preferred Primary Care Physicians, Inc.

Pittsburgh, Pennsylvania, 15236, United States

Location

Frontier Clinical Research, LLC

Scottdale, Pennsylvania, 15683, United States

Location

Montgomery Medical Inc.

Smithfield, Pennsylvania, 15478, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Coastal Pediatric Research

Charleston, South Carolina, 29414, United States

Location

Coastal Pediatrics Associates

Mt. Pleasant, South Carolina, 29464, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Hospital/Baylor College Medicine

Houston, Texas, 77030, United States

Location

Houston Clinical Research Associates

Houston, Texas, 77090, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

ClinPoint Trials

Waxahachie, Texas, 75165, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Virginia Tech Carilion School of Medicine Pediatric Gastroenterology

Roanoke, Virginia, 24013, United States

Location

MultiCare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Aurora Health Care, Aurora Medical Center in Summit

Summit, Wisconsin, 53066, United States

Location

Children's Hospital of Western Ontario

London, Ontario, N6A 5W9, Canada

Location

Physician's Clinical Research Inc.

Vaughan, Ontario, L4L 4Y7, Canada

Location

Related Publications (1)

• Di Lorenzo C, Nurko S, Hyams JS, Rodriguez-Araujo G, Shakhnovich V, Saps M, Simon M. Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation. J Pediatr Gastroenterol Nutr. 2024 Mar;78(3):539-547. doi: 10.1002/jpn3.12103. Epub 2023 Dec 28.

  PMID: 38504394 DERIVED

MeSH Terms

Interventions

linaclotide

Limitations and Caveats

Due to slow participant enrollment, further screening was terminated. This decision was not due to any safety concern.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Anna Muslin

  Forest Laboratories, LLC, an Allergan Affiliate

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: September 24, 2015
• Study Start: November 1, 2015
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: December 28, 2020
• Results First Posted: December 28, 2020

Record last verified: 2020-12

Locations

US (46); CA (2)