Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT05652205Other idM21-572Other id2022-501946-31-00

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Overview

Status: Completed
Phase: Phase 3
Enrollment: 123 participants (actual)
Sponsor: AbbVie · Industry
Design: Randomized · Quadruple masking
Countries: 4 countries
United States, Bulgaria, Netherlands, United Kingdom
Start: 29 Dec 2022
Primary completion: 2 Sept 2025
Completion: 2 Sept 2025
First posted: 15 Dec 2022
Last update posted: 14 May 2026
Conditions: Functional Constipation (FC) · Chronic Idiopathic Constipation (CIC)

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20222023202420252026

Ph 3
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
29 Dec 2022 to 2 Sept 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Placebo for LinaclotideDrug
LinaclotideDrug

Arms3

Placebo comparator
Part 1: Placebo for Linaclotide
Participants received placebo for linaclotide orally once daily (QD) for 12 weeks.
Experimental
Part 1: Linaclotide
Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks.
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.

Primary outcomes2

Outcomes the sponsor listed as primary.

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
Time frame · Baseline to Week 12
Registry description
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.
Number of Participants With Treatment-Emergent Adverse Events
Time frame · 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
Registry description
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.

Secondary outcomes(3)

Change From Baseline in 12-week Stool Consistency Observed by the Primary Caregiver During the Double-blind Study Intervention Period
Time frame · Baseline to Week 12
Registry description
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.
Change From Baseline in 12-week Straining Observed by the Primary Caregiver During the Double-blind Study Intervention Period
Time frame · Baseline to Week 12
Registry description
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.
Change From Baseline in 12-week Proportion of Days With Fecal Incontinence During the Double-blind Study Intervention Period (for Those With Toileting Skills)
Time frame · Baseline to Week 12
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline to Week 12

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

Group	Value (SBMs/week)	Spread
Part 1: Placebo for Linaclotide	1.418	0.2197
Part 1: Linaclotide	1.738	0.2188

Primary outcomeCount of participants· 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

Number of Participants With Treatment-Emergent Adverse Events

Group	Value (Participants)
Part 1: Placebo for Linaclotide	15
Part 1: Linaclotide	16
Part 2: Linaclotide	39

Secondary and other outcome results(3)

Secondary outcomeLeast squares mean· Baseline to Week 12

Change From Baseline in 12-week Stool Consistency Observed by the Primary Caregiver During the Double-blind Study Intervention Period

Group	Value (units on a scale)	Spread
Part 1: Placebo for Linaclotide	0.622	0.1162
Part 1: Linaclotide	0.998	0.1139

Secondary outcomeLeast squares mean· Baseline to Week 12

Change From Baseline in 12-week Straining Observed by the Primary Caregiver During the Double-blind Study Intervention Period

Group	Value (units on a scale)	Spread
Part 1: Placebo for Linaclotide	-0.526	0.0590
Part 1: Linaclotide	-0.542	0.0574

Secondary outcomeLeast squares mean· 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)

Group	Value (proportion of days)	Spread
Part 1: Placebo for Linaclotide	0.024	0.0139
Part 1: Linaclotide	0.018	0.0146

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Part 1: Placebo for LinaclotideParticipants received placebo for linaclotide orally once daily (QD) for 12 weeks.	0 / 61	0 / 61	5 / 61
Part 1: LinaclotideParticipants received 72 µg linaclotide orally once daily (QD) for 12 weeks.	0 / 62	0 / 62	6 / 62
Part 2: LinaclotideParticipants 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 (EudraCT 2019-002126-75) were assigned to receive open-label linaclotide 72 µg orally once daily (QD) for 24 weeks at the start of Part 2.	0 / 104	1 / 104	23 / 104

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 2 Years up to 5 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

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