A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With Linaclotide

A Phase 2 Dose Finding Study Evaluating the Safety and Efficacy of Linaclotide in Pediatric Subjects 6 Months to Less Than 2 Years of Age With Functional Constipation (FC).

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 who meet modified Rome IV criteria for childhood FC. In Part 1 of this study, participants are placed in 3 groups, which occur consecutively. Each group receives a different dosage of linaclotide. In Part 2 of the study, participants will be randomly assigned to receive either linaclotide or placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Up to 30 and at least 18 pediatric participants 6 months to less than 2 years of age with FC will be enrolled in the study at approximately 38 sites worldwide.

Participants will receive oral solution of linaclotide prepared from capsule by parent/guardian once daily for 4 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 regular 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
• Intervention / Treatment: Drug: Linaclotide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi /ID# 250808
  • Rousse, Bulgaria, 7002
    • UMHAT Kanev /ID# 248931
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda University Hospital EAD /ID# 251232
  • Sofia, Bulgaria, 1606
    • Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251229
  • Varna, Bulgaria, 9000
    • Nova Clinic /ID# 249023
• Croatia
  • City of Zagreb
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Sestre milosrdnice /ID# 252798
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Zagreb /ID# 252796
    • Zagreb, City of Zagreb, Croatia, 10000
      • Klinika za dječje bolesti Zagreb /ID# 252792
  • County of Osijek-Baranja
    • Osijek, County of Osijek-Baranja, Croatia, 31000
      • Klinicki bolnicki centar Osijek /ID# 252795
• Germany
  • Forchheim, Germany, 91301
    • Kinderarztpraxis Dr. Froehlich /ID# 252050
  • Wuppertal, Germany, 42283
    • HELIOS Klinikum Wuppertal /ID# 249022
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitaetsklinikum Muenster /ID# 251965
• Hungary
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, Hungary, 4032
      • Debreceni Egyetem-Klinikai Kozpont /ID# 250793
• Serbia
  • Novi Sad, Serbia, 21000
    • Institute for Child and Youth Health Care of Vojvodina /ID# 252482
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • University Children's Hospital 'Tirsova' /ID# 252483
    • Belgrade, Beograd, Serbia, 11000
      • Institut za zdravstvenu zastitu majke i deteta Srbije Dr Vukan Cupic /ID# 252485
• United Kingdom
  • Dudley, United Kingdom, DY1 2HQ
    • Russells Hall Hospital /ID# 252660
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3HZ
      • Great Ormond Street Children's Hospital /ID# 253333
    • London, Greater London, United Kingdom, E1 2ES
      • Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 252298
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 252299
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Velocity Clinical Research - Phoenix /ID# 263871
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • HealthStar Research of Hot Springs PLLC /ID# 251553
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center /ID# 248763
    • Corona, California, United States, 92879-3104
      • Kindred Medical Institute - Corona /ID# 251535
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20016-4300
      • Velocity Clinical Research Washington DC /ID# 263872
  • Florida
    • Doral, Florida, United States, 33166
      • Prohealth Research Center /ID# 248696
    • Miami, Florida, United States, 33155
      • South Miami Medical & Research Group Inc. /ID# 248765
    • Miami, Florida, United States, 33165
      • Valencia Medical & Research Center /ID# 251533
  • Georgia
    • Macon, Georgia, United States, 31210-6583
      • Velocity Clinical Research Macon /ID# 263959
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research - Lafayette /ID# 263873
  • Maryland
    • New Market, Maryland, United States, 21774-6154
      • Frederick County Pediatrics /ID# 251555
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Center of Medical Research /ID# 253536
  • Nebraska
    • Hastings, Nebraska, United States, 68901-2640
      • Velocity Clinical Research- Hastings Nebraska /ID# 260932
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research - West Ashley B /ID# 248693
    • Summerville, South Carolina, United States, 29486
      • Coastal Pediatric Research - Summerville /ID# 253534
  • Texas
    • Houston, Texas, United States, 77090-2633
      • Houston Clinical Research Associates /ID# 261571
    • Mansfield, Texas, United States, 76063
      • Prime Clinical Research - Mansfield - East Broad Street /ID# 262947
    • Waxahachie, Texas, United States, 75165-1430
      • ClinPoint Trials /ID# 251534

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals must be 6 months to less than 1 year and 11 months old, at the time the legally authorized representative (LAR)/parent/guardian signs the informed consent in alignment with local requirements.
• The LAR/parent/guardian who will be completing the electronic diary (eDiary) is able to read and understand the assessments in the eDiary device and must undergo training.

• Participant meets Rome IV criteria for functional constipation (FC): for at least 1 month before Screening (Visit 1), the participant must meet 2 or more of the following:

  • 2 or fewer defecations per week (with each defecation occurring in the absence of any laxative, suppository, or enema use during the preceding 24 hours)
  • History of excessive stool retention
  • History of painful or hard bowel movements (BMs)
  • History of large-diameter stools
  • Presence of a large fecal mass in the rectum
• LAR/Parent/Guardian is willing to discontinue any laxatives used before the Preintervention Visit in favor of the protocol-permitted rescue medicine.

Exclusion Criteria:

• Participant has conditions that could interfere with drug absorption, including, but not limited to, short bowel syndrome.
• History of clinically significant medical conditions or any other reason that the investigator determines would interfere with the individual's participation in this study or would make the participant an unsuitable candidate to receive study drug.

• Participant has 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 (investigator has confirmed an active anal fissure and participant reports known anal fissure symptoms [i.e., streaks of blood on the stool or on diaper or toilet paper and pain/crying with bowel movement 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 Rome IV FC criteria, the subject 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
  • 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 enrollment/randomization (Visit 3). A complete remission is defined as the disappearance of all signs of cancer in response to treatment)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Linaclotide Dose A; Linaclotide Dose A capsules, mixed with water and administered orally, once daily for 4 weeks	Drug: Linaclotide; Capsule; oral; Other Names: Linzess
Experimental: Part 1, Linaclotide Dose B; Linaclotide Dose B capsules, mixed with water and administered orally, once daily for 4 weeks	Drug: Linaclotide; Capsule; oral; Other Names: Linzess
Experimental: Part 1, Linaclotide Dose C; Linaclotide Dose C capsules, mixed with water and administered orally, once daily for 4 weeks	Drug: Linaclotide; Capsule; oral; Other Names: Linzess
Experimental: Part 2, Linaclotide; Participants will receive Linaclotide capsules mixed with water and administered orally in Part 2 for 4 weeks.	Drug: Linaclotide; Capsule; oral; Other Names: Linzess
Experimental: Part 2, Placebo; Participants will receive placebo capsules mixed with water and administered orally in Part 2 for 4 weeks.	Drug: Placebo; Capsule; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Overall Spontaneous Bowel Movement (SBM) Frequency Rate (SBMs/Week) During the 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 4-week SBM frequency rate.	Baseline to Week 4
Change From Baseline in Stool Consistency (Bristol Stool Form Scale) During the 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 4
Change From Baseline in Straining During the Study Intervention Period	Straining for each LAR/parent/guardian/caregiver-observed BM the child passes was collected daily in the eDiary device, using a 4-point scale (0 = No, not at all; 1 = Yes, a little; 2 = Yes, a lot; 3 = I don't know) based on two questions (did he/she grunt or make a face like he/she was straining). Lower value represents a better outcome and "I don't know" is considered as a missing response. The subject's average straining score for each caregiver-observed BM was derived based on the average of non-missing responses of the two straining questions. The participant's straining score in the 4-week Study Intervention Period was the average of the non-missing average straining scores from all caregiver-observed SBMs during the 4-week Study Intervention Period. If a subject had no caregiver-observed SBMs at baseline, then the baseline straining score reported by the caregiver was missing and, therefore, that subject was not included in the change from baseline straining analysis.	Baseline to Week 4
Number of Participants With Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study.	Up to Week 5

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2023
• Primary Completion (Actual): June 9, 2025
• Study Completion (Actual): June 9, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Linzess; Linaclotide; pediatric functional constipation
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Guanylyl Cyclase C Agonists; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Activators; linaclotide
• Other Study ID Numbers: M21-862; 2022-501947-34-00 (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; 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