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

NCT05760313 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: M21-8622022-501947-34-00
• Study Type: interventional
• Target: 19
• Locations: 7 countries
• Sites: 38

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 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.

Conditions

Functional Constipation

Keywords

Linaclotide; pediatric functional constipation; Linzess

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (5)

Part 1, Linaclotide Dose A

EXPERIMENTAL

Linaclotide Dose A capsules, mixed with water and administered orally, once daily for 4 weeks

Drug: Linaclotide

Part 1, Linaclotide Dose B

EXPERIMENTAL

Linaclotide Dose B capsules, mixed with water and administered orally, once daily for 4 weeks

Drug: Linaclotide

Part 1, Linaclotide Dose C

EXPERIMENTAL

Linaclotide Dose C capsules, mixed with water and administered orally, once daily for 4 weeks

Drug: Linaclotide

Part 2, Linaclotide

EXPERIMENTAL

Participants will receive Linaclotide capsules mixed with water and administered orally in Part 2 for 4 weeks.

Drug: Linaclotide

Part 2, Placebo

EXPERIMENTAL

Participants will receive placebo capsules mixed with water and administered orally in Part 2 for 4 weeks.

Drug: Placebo

Interventions

Linaclotide DRUG

Capsule; oral

Also known as: Linzess

Part 1, Linaclotide Dose A; Part 1, Linaclotide Dose B; Part 1, Linaclotide Dose C; Part 2, Linaclotide

Placebo DRUG

Capsule; oral

Part 2, Placebo

Eligibility Criteria

• Age: 6 Months - 23 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

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

Study Sites (38)

Velocity Clinical Research - Phoenix /ID# 263871

Phoenix, Arizona, 85006, United States

Location

HealthStar Research of Hot Springs PLLC /ID# 251553

Hot Springs, Arkansas, 71913, United States

Location

Advanced Research Center /ID# 248763

Anaheim, California, 92805, United States

Location

Kindred Medical Institute - Corona /ID# 251535

Corona, California, 92879-3104, United States

Location

Velocity Clinical Research Washington DC /ID# 263872

Washington D.C., District of Columbia, 20016-4300, United States

Location

Prohealth Research Center /ID# 248696

Doral, Florida, 33166, United States

Location

South Miami Medical & Research Group Inc. /ID# 248765

Miami, Florida, 33155, United States

Location

Valencia Medical & Research Center /ID# 251533

Miami, Florida, 33165, United States

Location

Velocity Clinical Research Macon /ID# 263959

Macon, Georgia, 31210-6583, United States

Location

Velocity Clinical Research - Lafayette /ID# 263873

Lafayette, Louisiana, 70508, United States

Location

Frederick County Pediatrics /ID# 251555

New Market, Maryland, 21774-6154, United States

Location

Michigan Center of Medical Research /ID# 253536

Farmington Hills, Michigan, 48334, United States

Location

Velocity Clinical Research- Hastings Nebraska /ID# 260932

Hastings, Nebraska, 68901-2640, United States

Location

Coastal Pediatric Research - West Ashley B /ID# 248693

Charleston, South Carolina, 29414, United States

Location

Coastal Pediatric Research - Summerville /ID# 253534

Summerville, South Carolina, 29486, United States

Location

Houston Clinical Research Associates /ID# 261571

Houston, Texas, 77090-2633, United States

Location

Prime Clinical Research - Mansfield - East Broad Street /ID# 262947

Mansfield, Texas, 76063, United States

Location

ClinPoint Trials /ID# 251534

Waxahachie, Texas, 75165-1430, United States

Location

UMHAT Sveti Georgi /ID# 250808

Plovdiv, 4002, Bulgaria

Location

UMHAT Kanev /ID# 248931

Rousse, 7002, Bulgaria

Location

Acibadem City Clinic Tokuda University Hospital EAD /ID# 251232

Sofia, 1407, Bulgaria

Location

Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251229

Sofia, 1606, Bulgaria

Location

Nova Clinic /ID# 249023

Varna, 9000, Bulgaria

Location

Klinicki bolnicki centar Sestre milosrdnice /ID# 252798

Zagreb, City of Zagreb, 10000, Croatia

Location

Klinicki bolnicki centar Zagreb /ID# 252796

Zagreb, City of Zagreb, 10000, Croatia

Location

Klinika za dječje bolesti Zagreb /ID# 252792

Zagreb, City of Zagreb, 10000, Croatia

Location

Klinicki bolnicki centar Osijek /ID# 252795

Osijek, County of Osijek-Baranja, 31000, Croatia

Location

Universitaetsklinikum Muenster /ID# 251965

Münster, North Rhine-Westphalia, 48149, Germany

Location

Kinderarztpraxis Dr. Froehlich /ID# 252050

Forchheim, 91301, Germany

Location

HELIOS Klinikum Wuppertal /ID# 249022

Wuppertal, 42283, Germany

Location

Debreceni Egyetem-Klinikai Kozpont /ID# 250793

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Institut za zdravstvenu zastitu majke i deteta Srbije Dr Vukan Cupic /ID# 252485

Belgrade, Beograd, 11000, Serbia

Location

University Children's Hospital 'Tirsova' /ID# 252483

Belgrade, Beograd, 11000, Serbia

Location

Institute for Child and Youth Health Care of Vojvodina /ID# 252482

Novi Sad, 21000, Serbia

Location

Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 252298

London, Greater London, E1 2ES, United Kingdom

Location

Great Ormond Street Children's Hospital /ID# 253333

London, Greater London, WC1N 3HZ, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 252299

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Russells Hall Hospital /ID# 252660

Dudley, DY1 2HQ, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Interventions

linaclotide

Results Point of Contact

• Title: ABBVIE CALL CENTER
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

844-663-3742

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: February 27, 2023
• First Posted: March 8, 2023
• Study Start: April 27, 2023
• Primary Completion: June 9, 2025
• Study Completion: June 9, 2025
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2026-01

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

SE (3); CR (4); BU (5); US (18); DE (3); HU (1); GB (4)