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Irritable Bowel Syndrome With ConstipationPhase 2LIN-MD-63NCT02559817

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

A Phase 2 study testing Linaclotide Dose A, Linaclotide Dose B and Linaclotide Dose C in people with Irritable Bowel Syndrome With Constipation, run by Forest Laboratories at 48 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 7 to 17 years
What is being tested?
Linaclotide Dose A, Linaclotide Dose B and Linaclotide Dose C
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
101 participants
Where
48 sitesin 2 countries
Study dates
1 Nov 2015to 30 Aug 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 7 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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:
Show all 13Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

48 sites in 2 countries.

48 sites in 2 countries

United States46 sites
  • Advanced Research Center - Site 069

    Anaheim, California, 92805

  • Asheboro Research Associates - Site 022

    Asheboro, North Carolina, 27203

  • Children's Center for Digestive Health Care LLC

    Atlanta, Georgia, 30342

  • Boys Town National Research Hospital

    Boys Town, Nebraska, 68010

  • Coastal Pediatric Research

    Charleston, South Carolina, 29414

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Kindred Medical Institute for Clinical Trials, LLC

    Corona, California, 92879

  • WCCT Global, LLC

    Costa Mesa, California, 92626

  • Ohio Pediatric Research Association

    Dayton, Ohio, 45414

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • HealthStar Research, LLC

    Hot Springs, Arkansas, 71913

  • Texas Children's Hospital/Baylor College Medicine

    Houston, Texas, 77030

  • Houston Clinical Research Associates

    Houston, Texas, 77090

  • Riley Hospital for Children at Indiana University Health

    Indianapolis, Indiana, 46202

  • GI Associates and Endoscopy Center

    Jackson, Mississippi, 39202

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Midwest Children Health Research Institute

    Lincoln, Nebraska, 68505

  • Midwest Children Health Research Institute

    Lincoln, Nebraska, 68516

  • Applied Research Center of Arkansas

    Little Rock, Arkansas, 72212

  • ACTCA, Inc

    Los Angeles, California, 90017

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Advanced Medical Research Center

    Miami, Florida, 33135

  • Goryeb Children's Hospital

    Morristown, New Jersey, 07962

  • Coastal Pediatrics Associates

    Mt. Pleasant, South Carolina, 29464

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

    New York, New York, 10032

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • IPS Research Company

    Oklahoma City, Oklahoma, 73103

  • Center for Clinical Trials, LLC

    Paramount, California, 90723

  • Methodist Medical Center

    Peoria, Illinois, 61602

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Preferred Primary Care Physicians, Inc.

    Pittsburgh, Pennsylvania, 15236

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Capital Pediatrics and Adolescent Center PLLC

    Raleigh, North Carolina, 27609

  • Virginia Tech Carilion School of Medicine Pediatric Gastroenterology

    Roanoke, Virginia, 24013

  • Sun Research Institute

    San Antonio, Texas, 78215

  • University of California at San Francisco

    San Francisco, California, 94143

  • Frontier Clinical Research, LLC

    Scottdale, Pennsylvania, 15683

  • Willis-Knighton Physician Network

    Shreveport, Louisiana, 71118

  • Certified Research Consultants Virgo/Carter Pediatrics

    Silver Spring, Maryland, 20910

  • Montgomery Medical Inc.

    Smithfield, Pennsylvania, 15478

  • Sleepcare Clinical Research Institute

    Stockbridge, Georgia, 30281

  • Aurora Health Care, Aurora Medical Center in Summit

    Summit, Wisconsin, 53066

  • MultiCare Institute for Research and Innovation

    Tacoma, Washington, 98405

  • ClinPoint Trials

    Waxahachie, Texas, 75165

  • Heartland Research Associates, LLC

    Wichita, Kansas, 67205

Other trials in United States

Canada2 sites
  • Children's Hospital of Western Ontario

    London, Ontario, N6A 5W9

  • Physician's Clinical Research Inc.

    Vaughan, Ontario, L4L 4Y7

Other trials in Canada

About this study

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

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.

Being tested
Linaclotide Dose A, Linaclotide Dose B, Linaclotide Dose C, Linaclotide Approved Adult Dose, Matching Placebo
Keywords
Irritable Bowel Syndrome with Constipation in children, Linzess

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Linaclotide Dose ADrug

    Also called Linzess

  • Linaclotide Dose BDrug

    Also called Linzess

  • Linaclotide Dose CDrug

    Also called Linzess

  • Linaclotide Approved Adult DoseDrug

    Also called Linzess

  • Matching PlaceboDrug

    Also called Linzess

Study groups in NCT02559817
Study groupRoleWhat they receive
Linaclotide Dose AExperimentalTaken 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
Receives: Drug: Linaclotide Dose A
Linaclotide Dose BExperimentalTaken 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
Receives: Drug: Linaclotide Dose B
Linaclotide Dose CExperimentalTaken 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
Receives: Drug: Linaclotide Dose C
Linaclotide Approved Adult DoseExperimentalTaken 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
Receives: Drug: Linaclotide Approved Adult Dose
Matching PlaceboPlacebo comparatorTaken 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
Receives: Drug: Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)
  1. 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.

    Measured: Baseline (14 days prior to randomization) to week 4

  2. 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.

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

  3. 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.

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

  4. 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.

    Measured: Baseline (14 days prior to randomization) to week 4

  5. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2015 (estimated)
  2. Study start1 Nov 2015
  3. Primary completion30 Aug 2019
  4. Study completion30 Aug 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02559817
Sponsor's protocol ID
LIN-MD-63
Acronym
LIN-MD-63
Status last verified
Dec 2020
First submitted
23 Sep 2015
Last updated
28 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38504394

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Linaclotide Dose A, Linaclotide Dose B and Linaclotide Dose C in people with Irritable Bowel Syndrome With Constipation, run by Forest Laboratories at 48 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Treatment Period (time frame: Baseline (14 days prior to randomization and up to randomization) to week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02559817, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2020.

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