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

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Rousse, Bulgaria, 7002
    • UMHAT Kanev /ID# 250815
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda University Hospital EAD /ID# 251234
  • Sofia, Bulgaria, 1606
    • Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251233
  • Varna, Bulgaria, 9000
    • Nova Clinic /ID# 250816
  • Plovdiv
    • Tsentar, Plovdiv, Bulgaria, 4001
      • University Hospital Plovdiv /ID# 250814
• Netherlands
  • North Brabant
    • Breda, North Brabant, Netherlands, 4818 CK
      • Amphia Ziekenhuis /ID# 251698
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam UMC, locatie AMC /ID# 251295
• United Kingdom
  • Armthorpe Road, United Kingdom, DN2 5LT
    • Doncaster Royal Infirmary /ID# 252080
  • Grimsby, United Kingdom, DN33 2BA
    • Northern Licolnshire and Goole NHS Foundation Trust /ID# 252007
  • Greater London
    • London, Greater London, United Kingdom, E1 2ES
      • Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 251179
• United States
  • Alabama
    • Foley, Alabama, United States, 36535
      • G & L Research, LLC /ID# 250658
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Velocity Clinical Research - Phoenix /ID# 266280
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research of Hot Springs PLLC /ID# 249481
    • Little Rock, Arkansas, United States, 72212-4187
      • Applied Research Center of Arkansas /ID# 249764
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center /ID# 249412
    • Corona, California, United States, 92879-3104
      • Kindred Medical Institute - Corona /ID# 249485
    • San Diego, California, United States, 92108
      • Medical Ctr for Clin Research /ID# 254386
  • Florida
    • Doral, Florida, United States, 33166
      • Prohealth Research Center /ID# 249420
    • Hollywood, Florida, United States, 33021-6030
      • KIDZ Medical Services - Hollywood /ID# 250823
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System /ID# 250881
    • Kissimmee, Florida, United States, 34741
      • Kissimmee Clinical Research /ID# 252206
    • Miami, Florida, United States, 33155
      • South Miami Medical & Research Group Inc. /ID# 249418
    • Miami, Florida, United States, 33165
      • Valencia Medical & Research Center /ID# 250452
    • Miami, Florida, United States, 33172
      • Palmetto Professional Research /ID# 250875
    • Miami Springs, Florida, United States, 33166-7225
      • South Florida Research Ph I-IV /ID# 252350
  • Georgia
    • Macon, Georgia, United States, 31210-6583
      • Velocity Clinical Research Macon /ID# 266516
    • Union City, Georgia, United States, 30291
      • Rophe Adult & Pediatric Medicine /ID# 250663
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Michael W. Simon, MD, PSC /ID# 250664
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research - Lafayette /ID# 266751
  • Maryland
    • New Market, Maryland, United States, 21774-6154
      • Frederick County Pediatrics /ID# 249483
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Center of Medical Research /ID# 251088
  • Minnesota
    • Minneapolis, Minnesota, United States, 55413-2195
      • MNGI Digestive Health, P. A. /ID# 249676
  • Nebraska
    • Hastings, Nebraska, United States, 68901-2640
      • Velocity Clinical Research- Hastings Nebraska /ID# 252132
  • New Jersey
    • Newark, New Jersey, United States, 07103-2425
      • Rutgers New Jersey Medical School Campus, Doctors Office Center /ID# 250876
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514-4220
      • Univ NC Chapel Hill /ID# 252044
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center /ID# 250893
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company /ID# 250822
  • Pennsylvania
    • Scottdale, Pennsylvania, United States, 15683
      • Frontier Clinical Research, LLC - Scottdale /ID# 250656
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research - Smithfield /ID# 250657
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research - West Ashley B /ID# 249413
    • Greenville, South Carolina, United States, 29607-4021
      • Tribe Clinical Research LLC /ID# 255656
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatric Research - Summerville /ID# 249423
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Tullahoma Pediatrics /ID# 250892
  • Texas
    • Houston, Texas, United States, 77090-2633
      • Houston Clinical Research Associates /ID# 250779
    • Mansfield, Texas, United States, 76063
      • Prime Clinical Research - Mansfield - East Broad Street /ID# 266236
    • Waxahachie, Texas, United States, 75165-1430
      • ClinPoint Trials /ID# 250448
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center /ID# 249790
  • West Virginia
    • Kingwood, West Virginia, United States, 26537-9797
      • 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
Placebo Comparator: Part 1: Placebo for Linaclotide; Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.	Drug: Placebo for Linaclotide; Capsule; oral
Experimental: Part 1: Linaclotide; Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.	Drug: Linaclotide; Capsule; oral
Experimental: Part 2: Linaclotide; Participants who received 72 µg linaclotide or placebo in Part 1 of this study or who entered Part 2 of this study from Study LIN-MD-67 (NCT04110145) were assigned to receive open-label linaclotide 72 µg orally once daily (QD) for 24 weeks at the start of Part 2.	Drug: Linaclotide; Capsule; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 12-week 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 values for efficacy endpoints related to daily eDiary responses were derived from the eDiary in the preintervention period, specifically the time period from 14 days before randomization and up to the time of randomization.	Baseline to Week 12
Number of Participants With Treatment-Emergent Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient/clinical investigation subject administered a pharmaceutical product which doesn't necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.	From the time of study drug administration until 30 days or 5 half-lives after the last dose, up to 126 days in Period 1 and 226 days in Period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 12-week Stool Consistency Observed by the Primary Caregiver During the Double-blind Study Intervention Period	The caregiver/parent/guardian/legally authorized representative (LAR) rated and recorded 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. A response of "I don't know" was considered as a missing score. Lower scores indicate firmer stool consistency. A subject's stool consistency score for the study intervention period is the average of the non-missing BSFS scores for the primary caregiver-observed SBMs during that specific period.	Baseline to Week 12
Change From Baseline in 12-week Straining Observed by the Primary Caregiver During the Double-blind Study Intervention Period	The caregiver/parent/guardian/LAR rated and recorded in an eDiary the amount of straining they observed when the child passed the BM using two 3-point rating scales:. 1) For the bowel movement #X you were with the child for, did he/she grunt like he/she was straining? 0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; I don't know. 2) For the bowel movement #X you were with the child for, did he/she make a face like he/she was straining? 0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; I don't know. "I don't know" was considered a missing response. Higher scores indicate more straining. The subject's straining score was the average of the nonmissing average straining scores for all the primary caregiver-observed SBMs during the specific period.	Baseline to Week 12
Change From Baseline in 12-week Proportion of Days With Fecal Incontinence During the Double-blind Study Intervention Period (for Those With Toileting Skills)	Caregivers of children who have acquired toileting skills for BMs were asked about their child's fecal incontinence episodes. Toileting skills were assessed as part of the first daily diary, modified daily diary, or clinic diary and responses were carried through to the completion of the study.	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 (Actual): September 2, 2025
• Study Completion (Actual): September 2, 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): May 14, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Linzess; Linaclotide; Functional Constipation (FC); AGN-182139
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Substandard Drugs; Pharmaceutical Preparations; 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 clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: To learn more about 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

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