A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation

A Phase 3, Multicenter, Randomized, Double-blind, Parallel-group, Safety and Efficacy Study of Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional Constipation (FC) With a 24-week Open-label Treatment Extension

Functional constipation (FC) is a common healthcare problem in children of all ages, potentially due to genetic predisposition, inadequate fiber and fluid intake, and immobility. Currently, there are no pharmacological therapies approved for the treatment of FC. This study will assess adverse events and change in disease activity with linaclotide therapy in participants with FC.

Linaclotide is an approved drug being developed for the treatment of FC in pediatric patients, ages 2 to 5, who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. All participants in Part 2 will receive linaclotide. Approximately 116 participants aged 2 to 5 years with FC will be enrolled in this study at around 45 sites worldwide.

Participants will receive daily doses of oral Linaclotide capsules or matching placebo for 12 weeks in Part 1 of the study. In Part 2, the open label long-term safety extension, participants with FC who completed study intervention in Part 1 of Study M21-572 or the Phase 2 Study LIN-MD-67 will receive linaclotide for 24 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Functional Constipation (FC); Chronic Idiopathic Constipation (CIC)
• Intervention / Treatment: Drug: Linaclotide; Drug: Placebo for Linaclotide

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Bulgaria
  • Ruse, Bulgaria, 7002
    • Recruiting
    • UMHAT Kanev /ID# 250815
  • Sofia, Bulgaria, 1407
    • Recruiting
    • Acibadem City Clinic Tokuda University Hospital EAD /ID# 251234
  • Sofiya, Bulgaria, 1606
    • Recruiting
    • Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251233
  • Varna, Bulgaria, 9000
    • Recruiting
    • Nova Clinic /ID# 250816
    • Contact: Site Coordinator; Phone Number: +359700 17 340
  • Plovdiv
    • Tsentar, Plovdiv, Bulgaria, 4001
      • Recruiting
      • University Hospital Plovdiv /ID# 250814
• Netherlands
  • Noord-Brabant
    • Breda, Noord-Brabant, Netherlands, 4818 CK
      • Recruiting
      • Amphia Ziekenhuis /ID# 251698
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Academisch Medisch Centrum /ID# 251295
• United Kingdom
  • Armthorpe Road, United Kingdom, DN2 5LT
    • Recruiting
    • Doncaster Royal Infirmary /ID# 252080
  • Grimsby, United Kingdom, DN33 2BA
    • Recruiting
    • Northern Licolnshire and Goole NHS Foundation Trust /ID# 252007
  • London, City Of
    • London, London, City Of, United Kingdom, E1 2ES
      • Recruiting
      • Barts Health NHS Trust /ID# 251179
• United States
  • Alabama
    • Foley, Alabama, United States, 36535
      • Recruiting
      • G & L Research, LLC /ID# 250658
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Recruiting
      • HealthStar Research of Hot Springs PLLC /ID# 249481
    • Little Rock, Arkansas, United States, 72212-4187
      • Recruiting
      • Applied Research Center of Arkansas /ID# 249764
  • California
    • Anaheim, California, United States, 92805
      • Recruiting
      • Advanced Research Center /ID# 249412
    • Corona, California, United States, 92879-3104
      • Recruiting
      • Kindred Medical Institute - Corona /ID# 249485
    • San Diego, California, United States, 92108
      • Recruiting
      • Medical Ctr for Clin Research /ID# 254386
  • Florida
    • Doral, Florida, United States, 33166
      • Recruiting
      • Prohealth Research Center /ID# 249420
    • Hollywood, Florida, United States, 33021-6030
      • Recruiting
      • KIDZ Medical Services - Hollywood /ID# 250823
    • Kissimmee, Florida, United States, 34741
      • Recruiting
      • Kissimmee Clinical Research /ID# 252206
    • Miami, Florida, United States, 33165
      • Recruiting
      • Valencia Medical & Research Center /ID# 250452
    • Miami, Florida, United States, 33155
      • Recruiting
      • South Miami Medical & Research Group Inc. /ID# 249418
    • Miami, Florida, United States, 33172
      • Recruiting
      • Palmetto Professional Research /ID# 250875
    • Miami Springs, Florida, United States, 33166-7225
      • Recruiting
      • South Florida Research Ph I-IV /ID# 252350
  • Georgia
    • Union City, Georgia, United States, 30291
      • Recruiting
      • Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 250663
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Recruiting
      • Michael W. Simon, MD, PSC /ID# 250664
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Recruiting
      • Virgo Carter Pediatrics /ID# 249483
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Michigan Center of Medical Research /ID# 251088
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413-2195
      • Recruiting
      • MNGI Digestive Health, P. A. /ID# 249676
  • Nebraska
    • Hastings, Nebraska, United States, 68901-2640
      • Recruiting
      • Velocity Clinical Research- Hastings Nebraska /ID# 252132
      • Contact: Site Coordinator; Phone Number: 402-407-2800
  • New Jersey
    • Newark, New Jersey, United States, 07103-2425
      • Recruiting
      • Rutgers New Jersey Medical School Campus, Doctors Office Center /ID# 250876
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514-4220
      • Recruiting
      • Univ NC Chapel Hill /ID# 252044
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • UH Cleveland Medical Center /ID# 250893
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • Completed
      • IPS Research Company /ID# 250822
  • Pennsylvania
    • Scottdale, Pennsylvania, United States, 15683
      • Recruiting
      • Frontier Clinical Research, LLC - Scottdale /ID# 250656
    • Smithfield, Pennsylvania, United States, 15478
      • Recruiting
      • Frontier Clinical Research /ID# 250657
      • Contact: Site Coordinator; Phone Number: (724) 569-8036
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Recruiting
      • Coastal Pediatric Research - West Ashley B /ID# 249413
    • Greenville, South Carolina, United States, 29607-4021
      • Recruiting
      • Tribe Clinical Research LLC /ID# 255656
    • Summerville, South Carolina, United States, 29486
      • Recruiting
      • Coastal Pediatric Research - Summerville /ID# 249423
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Recruiting
      • Tullahoma Pediatrics /ID# 250892
  • Texas
    • Houston, Texas, United States, 77090-2633
      • Recruiting
      • Houston Clinical Research Associates /ID# 250779
    • Waxahachie, Texas, United States, 75165-1430
      • Recruiting
      • ClinPoint Trials /ID# 250448
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Carilion Medical Center /ID# 249790
  • West Virginia
    • Kingwood, West Virginia, United States, 26537-9797
      • Recruiting
      • Frontier Clinical Research - Kingwood /ID# 251154

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Caregiver/parent/guardian/legally authorized representative (LAR) is willing and able to comply with procedures required in this protocol, prior to the initiation of any screening or study-specific procedures. In addition, the caregiver/parent/guardian/LAR who will be completing the electronic diary (eDiary) must be able to read and understand the assessments in the eDiary device and undergo training.

• Participant meets modified Rome IV criteria for FC: For at least 1 month before Screening (Visit 1), 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) per week. In addition, at least once per week, participant must meet 1 or more of the following:

  • History of retentive posturing or excessive volitional stool retention.
  • History of painful or hard bowel movements (BMs).
  • Presence of a large fecal mass in the rectum.
  • History of large diameter stools.
  • At least 1 episode of fecal incontinence per week after the acquisition of toileting skills, if applicable.

Exclusion Criteria:

• Participant history of:

  • Celiac disease, or positive serological test for celiac disease or the condition is suspected but has not been ruled out by endoscopic biopsy
  • Cystic fibrosis
  • Hypothyroidism that is untreated or treated with thyroid hormone at a dose that has not been stable for at least 3 months prior to Screening (Visit 1)
  • Down's syndrome or any other chromosomal disorder
  • Active anal fissure (i.e., participant reports having streaks of blood on the stool or on toilet paper and/or pain/crying with BM within 2 weeks prior to Screening). (Note: anal fissures that have resolved at least 2 weeks prior to screening would not be exclusionary.) However, if in the investigator's opinion, an anal fissure(s) may be the primary cause of participant's modified Rome IV FC criteria, the participant would not be eligible to participate in the study.
  • Anatomic malformations (e.g., imperforate anus, anal stenosis, anterior displaced anus)
  • Intestinal nerve or muscle disorders (e.g., Hirschprung disease, visceral myopathies, visceral neuropathies)
  • Neuropathic conditions (e.g., spinal cord abnormalities, neurofibromatosis, tethered cord, spinal cord trauma)
  • Lead toxicity, hypercalcemia
  • Inflammatory bowel disease
  • Childhood functional abdominal pain syndrome
  • Poorly treated or poorly controlled psychiatric disorders that might influence his or her ability to participate in the study
  • Lactose intolerance that is associated with symptoms which could confound the assessments in this study
  • History of cancer. (Note: participants with a history of cancer are allowed provided that the malignancy has been in a complete remission before Randomization (Visit 2). A complete remission is defined as the disappearance of all signs of cancer in response to treatment.)
• Has conditions that could interfere with drug absorption including but not limited to short bowel syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Linaclotide; Participants will receive linaclotide for 12 weeks.	Drug: Linaclotide; Capsule; oral
Experimental: Part 1 Placebo; Participants will receive placebo for 12 weeks.	Drug: Placebo for Linaclotide; Capsule; oral
Experimental: Part 2 Linaclotide; Participants who completed study intervention in Part 1 of this study or the Phase 2 Study LIN-MD-67 will receive 24 weeks of linaclotide exposure.	Drug: Linaclotide; Capsule; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the spontaneous bowel movement (SBM) frequency rate (SBMs/week) observed by the primary caregiver during the double-blind study intervention period.	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. The caregiver/parent/guardian/legally authorized representative (LAR) will complete the electronic diary (eDiary), providing data for the SBM frequency rate up to the last dose date equivalent to the 12-week SBM frequency rate.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of days with fecal incontinence during the double-blind study intervention period (for participants who have acquired toileting skills during daytime and nighttime or acquired toileting skills during daytime only)	Each day the caregiver/parent/guardian/LAR will record incidents of fecal incontinence in an eDiary.	Baseline to Week 12
Change from baseline in stool consistency observed by the primary caregiver during the double blind study intervention period	The caregiver/parent/guardian/legally authorized representative (LAR) will rate and record in an eDiary the consistency of the stool for each BM using the Bristol Stool Form 7-point scale in which 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; and 7=Watery, no solid pieces, entirely liquid.	Baseline to Week 12
Change from baseline in straining observed by the primary caregiver during the double-blind study intervention period	The caregiver/parent/guardian/LAR will rate and record in an eDiary the amount of straining they observe when the child passes the BM.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Estimated): August 15, 2025
• Study Completion (Estimated): November 14, 2025

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Linzess; Linaclotide; Functional Constipation (FC); AGN-182139
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: M21-572; 2022-501946-31-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes