Linaclotide Safety and Efficacy in 2 to 5-Year-Old Participants With Functional Constipation

Study at a glance

From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Sequential, Ascending, Multidose Study to Evaluate the Safety and Efficacy of Linaclotide in Pediatric Participants (Age 2 to 5 Years) With Functional Constipation

ClinicalTrials.gov ID

NCT04110145

Acronym / sponsor ID

LIN-MD-67

Conditions

Functional Constipation

Keywords

Functional constipation in children, LINZESS

Phase

Phase 2

Study type

Interventional

Recruitment status

Completed

Enrolment

35 participants (actual)

Lead sponsor

AllerganIndustry (pharma, biotech, devices)

Collaborators

Ironwood Pharmaceuticals, Inc.

Study start

14 Oct 2019 (actual)

Primary completion

20 Apr 2021 (actual)

Study completion

20 Apr 2021 (actual)

First posted

1 Oct 2019 (actual)

Results

Posted 26 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Sequential

Masking

Triple blind (participant, care provider, investigator)

Number of arms

5

Model description

There are 3 cohorts with ascending doses and an additional final cohort to repeat the highest dose determined to be safe

Who may qualify

Ages

2 to 5 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Child

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Change From Baseline in 4-week Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the Study Intervention Period of Each Cohort

   Time frame: Baseline (14 days prior to randomization) to Day 29

   A SBM was defined as a bowel movement (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. Each day the caregiver recorded the number of SBMs in the last 24 hours in an electronic diary (eDiary). The SBM frequency rate (SBMs/week) during the analysis period for each participant was 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.

2. Change From Baseline in 4-week Stool Consistency Reported by the Caregiver During the Study Intervention Period of Each Cohort

   Time frame: Baseline (14 days prior to randomization) to Day 29

   The caregiver rated and recorded in an eDiary the consistency of the stool for each bowel movement using the Bristol Stool Form 7-point scale where: 1=Separate hard lumps, like nuts (hard to pass); 2=Sausage-shaped, but lumpy; 3=Like a sausage but with cracks on its surface; 4=Like a sausage or snake, smooth and soft; 5=Soft blobs with clear cut edges (easy to pass); 6=Fluffy pieces with ragged edges, a mushy stool; 7=Watery, no solid pieces. Entirely liquid. Baseline value was based on values collected 14 days before randomization up to randomization. A participant's stool consistency score for the treatment period was the average of the nonmissing consistency scores from the BMs recorded by the caregiver during the 4-week treatment period.

3. Change From Baseline in 4-week Straining Reported by the Caregiver During the Study Intervention Period of Each Cohort

   Time frame: Baseline (14 days prior to randomization) to Day 29

   The caregiver rated and recorded in an eDiary the amount of straining they observed when the child passed the BM (1=Not at all; 2=Yes a little; 3=Yes a lot; I don't know). Baseline value was based on values collected 14 days before randomization up to randomization. A participant's straining score for the treatment period was the average of the nonmissing straining scores from the BMs recorded by the caregiver during the 4-week treatment period. A negative change from Baseline indicates improvement.

4. Percentage of Days With Fecal Incontinence During the Study Intervention Period (for Participants Who Have Acquired Toileting Skills During the Daytime and Nighttime or Acquired Toileting Skills During Daytime Only) Within Each Cohort

   Time frame: 29 Days

   Each day the caregiver recorded in an eDiary if the child had a bowel movement accident (Yes; No; I don't know). The percentage of days with fecal incontinence for the treatment period was the average of the nonmissing incidences of fecal incontinence recorded by the caregiver during the 4-week treatment period.

5. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

   Time frame: First dose of study drug intervention to within 1 week of last dose (Up to 45 days)

   An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that begins or worsens after receiving study drug. Safety Population included all participants in the Randomized Population who received at least 1 dose of double-blind study intervention.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 38962910Di Lorenzo C, Robert J, Rodriguez-Araujo G, Shakhnovich V, Xie W, Nurko S, Saps M. Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study. J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):510-518. doi: 10.1002/jpn3.12306. Epub 2024 Jul 4.
• Individual participant dataSharing planned: Yes. Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.

Related trials for Functional Constipation

• RecruitingPhase 2

  A Study of Brenipatide (LY3537031) in Participants With Irritable Bowel Syndrome-Constipation (IBS-C)

  Irritable Bowel Syndrome, Constipation

• Active, not recruitingPhase 2

  This is a Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group Study of the Efficacy and Safety of 2 Weight-based Treatment Groups of Plecanatide Versus Placebo in Children and Adolescent Participants 6 to Less Than 18 Years of Age With FC

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• Not yet recruitingPhase 3

  Rifaximin Treatment in Bloating Predominant Functional Bowel Disorders

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• Recruiting

  Effects of Connective Tissue Massage Plus Biofeedback for Dyssynergic Defecation

  Dyssynergic Defecation

• RecruitingObservational study

  Relationship Between Interoception and Postural Control in Constipation-Predominant Irritable Bowel Syndrome

  Constipation, Irritable Bowel Disease

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

18 sites in 1 country: see every site and its status.