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

NCT05652205 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: M21-5722022-501946-31-00
• Study Type: interventional
• Target: 123
• Locations: 4 countries
• Sites: 48

Brief Summary

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.

Conditions

Functional Constipation (FC); Chronic Idiopathic Constipation (CIC)

Keywords

Functional Constipation (FC); Linaclotide; AGN-182139; Linzess

Outcome Measures

Primary Outcomes (2)

• 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

• Number of Participants with Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

  Up to Approximately 36 Weeks

Secondary Outcomes (3)

• Change from baseline in stool consistency observed by the primary caregiver during the double blind study intervention period

  Baseline to Week 12

• Change from baseline in straining observed by the primary caregiver during the double-blind study intervention period

  Baseline to Week 12

• Change from baseline in 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)

  Baseline to Week 12

Study Arms (3)

Part 1 Linaclotide

EXPERIMENTAL

Participants will receive linaclotide for 12 weeks.

Drug: Linaclotide

Part 1 Placebo

EXPERIMENTAL

Participants will receive placebo for 12 weeks.

Drug: Placebo for Linaclotide

Part 2 Linaclotide

EXPERIMENTAL

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

Interventions

Linaclotide DRUG

Capsule; oral

Part 1 Linaclotide; Part 2 Linaclotide

Placebo for Linaclotide DRUG

Capsule; oral

Part 1 Placebo

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• AbbVie: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (48)

G & L Research, LLC /ID# 250658

Foley, Alabama, 36535, United States

Location

Velocity Clinical Research - Phoenix /ID# 266280

Phoenix, Arizona, 85006, United States

Location

HealthStar Research of Hot Springs PLLC /ID# 249481

Hot Springs, Arkansas, 71913, United States

Location

Applied Research Center of Arkansas /ID# 249764

Little Rock, Arkansas, 72212-4187, United States

Location

Advanced Research Center /ID# 249412

Anaheim, California, 92805, United States

Location

Kindred Medical Institute - Corona /ID# 249485

Corona, California, 92879-3104, United States

Location

Medical Ctr for Clin Research /ID# 254386

San Diego, California, 92108, United States

Location

Prohealth Research Center /ID# 249420

Doral, Florida, 33166, United States

Location

KIDZ Medical Services - Hollywood /ID# 250823

Hollywood, Florida, 33021-6030, United States

Location

Nemours Children's Health System /ID# 250881

Jacksonville, Florida, 32207, United States

Location

Kissimmee Clinical Research /ID# 252206

Kissimmee, Florida, 34741, United States

Location

South Miami Medical & Research Group Inc. /ID# 249418

Miami, Florida, 33155, United States

Location

Valencia Medical & Research Center /ID# 250452

Miami, Florida, 33165, United States

Location

Palmetto Professional Research /ID# 250875

Miami, Florida, 33172, United States

Location

South Florida Research Ph I-IV /ID# 252350

Miami Springs, Florida, 33166-7225, United States

Location

Velocity Clinical Research Macon /ID# 266516

Macon, Georgia, 31210-6583, United States

Location

Rophe Adult & Pediatric Medicine /ID# 250663

Union City, Georgia, 30291, United States

Location

Michael W. Simon, MD, PSC /ID# 250664

Lexington, Kentucky, 40517, United States

Location

Velocity Clinical Research - Lafayette /ID# 266751

Lafayette, Louisiana, 70508, United States

Location

Frederick County Pediatrics /ID# 249483

New Market, Maryland, 21774-6154, United States

Location

Michigan Center of Medical Research /ID# 251088

Farmington Hills, Michigan, 48334, United States

Location

MNGI Digestive Health, P. A. /ID# 249676

Minneapolis, Minnesota, 55413-2195, United States

Location

Velocity Clinical Research- Hastings Nebraska /ID# 252132

Hastings, Nebraska, 68901-2640, United States

Location

Rutgers New Jersey Medical School Campus, Doctors Office Center /ID# 250876

Newark, New Jersey, 07103-2425, United States

Location

Univ NC Chapel Hill /ID# 252044

Chapel Hill, North Carolina, 27514-4220, United States

Location

UH Cleveland Medical Center /ID# 250893

Cleveland, Ohio, 44106, United States

Location

IPS Research Company /ID# 250822

Oklahoma City, Oklahoma, 73106, United States

Location

Frontier Clinical Research, LLC - Scottdale /ID# 250656

Scottdale, Pennsylvania, 15683, United States

Location

Frontier Clinical Research - Smithfield /ID# 250657

Smithfield, Pennsylvania, 15478, United States

Location

Coastal Pediatric Research - West Ashley B /ID# 249413

Charleston, South Carolina, 29414, United States

Location

Tribe Clinical Research LLC /ID# 255656

Greenville, South Carolina, 29607-4021, United States

Location

Coastal Pediatric Research - Summerville /ID# 249423

Summerville, South Carolina, 29486, United States

Location

Tullahoma Pediatrics /ID# 250892

Tullahoma, Tennessee, 37388, United States

Location

Houston Clinical Research Associates /ID# 250779

Houston, Texas, 77090-2633, United States

Location

Prime Clinical Research - Mansfield - East Broad Street /ID# 266236

Mansfield, Texas, 76063, United States

Location

ClinPoint Trials /ID# 250448

Waxahachie, Texas, 75165-1430, United States

Location

Carilion Medical Center /ID# 249790

Roanoke, Virginia, 24014, United States

Location

Frontier Clinical Research - Kingwood /ID# 251154

Kingwood, West Virginia, 26537-9797, United States

Location

University Hospital Plovdiv /ID# 250814

Tsentar, Plovdiv, 4001, Bulgaria

Location

UMHAT Kanev /ID# 250815

Rousse, 7002, Bulgaria

Location

Acibadem City Clinic Tokuda University Hospital EAD /ID# 251234

Sofia, 1407, Bulgaria

Location

Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251233

Sofia, 1606, Bulgaria

Location

Nova Clinic /ID# 250816

Varna, 9000, Bulgaria

Location

Amphia Ziekenhuis /ID# 251698

Breda, North Brabant, 4818 CK, Netherlands

Location

Amsterdam UMC, locatie AMC /ID# 251295

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 251179

London, Greater London, E1 2ES, United Kingdom

Location

Doncaster Royal Infirmary /ID# 252080

Armthorpe Road, DN2 5LT, United Kingdom

Location

Northern Licolnshire and Goole NHS Foundation Trust /ID# 252007

Grimsby, DN33 2BA, United Kingdom

Location

Related Links

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

MeSH Terms

Interventions

linaclotide

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 15, 2022
• Study Start: December 29, 2022
• Primary Completion: September 2, 2025
• Study Completion: September 2, 2025
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/

Locations

NL (2); US (38); GB (3); BU (5)