Functional Constipation (FC)Phase 3NCT05652205
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 study testing Linaclotide in people with Functional Constipation (FC) and Chronic Idiopathic Constipation (CIC), run by AbbVie at 48 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 5 years
- Conditions the study is for
- Functional Constipation (FC), Chronic Idiopathic Constipation (CIC)
- What is being tested?
- Linaclotide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 48 sitesin 4 countries
- Study dates
- 29 Dec 2022to 2 Sep 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
48 sites in 4 countries.
48 sites in 4 countries
United States38 sites
Advanced Research Center /ID# 249412
Anaheim, California, 92805
Univ NC Chapel Hill /ID# 252044
Chapel Hill, North Carolina, 27514-4220
Coastal Pediatric Research - West Ashley B /ID# 249413
Charleston, South Carolina, 29414
UH Cleveland Medical Center /ID# 250893
Cleveland, Ohio, 44106
Kindred Medical Institute - Corona /ID# 249485
Corona, California, 92879-3104
Prohealth Research Center /ID# 249420
Doral, Florida, 33166
Michigan Center of Medical Research /ID# 251088
Farmington Hills, Michigan, 48334
G & L Research, LLC /ID# 250658
Foley, Alabama, 36535
Tribe Clinical Research LLC /ID# 255656
Greenville, South Carolina, 29607-4021
Velocity Clinical Research- Hastings Nebraska /ID# 252132
Hastings, Nebraska, 68901-2640
KIDZ Medical Services - Hollywood /ID# 250823
Hollywood, Florida, 33021-6030
HealthStar Research of Hot Springs PLLC /ID# 249481
Hot Springs, Arkansas, 71913
Houston Clinical Research Associates /ID# 250779
Houston, Texas, 77090-2633
Nemours Children's Health System /ID# 250881
Jacksonville, Florida, 32207
Frontier Clinical Research - Kingwood /ID# 251154
Kingwood, West Virginia, 26537-9797
Kissimmee Clinical Research /ID# 252206
Kissimmee, Florida, 34741
Velocity Clinical Research - Lafayette /ID# 266751
Lafayette, Louisiana, 70508
Michael W. Simon, MD, PSC /ID# 250664
Lexington, Kentucky, 40517
Applied Research Center of Arkansas /ID# 249764
Little Rock, Arkansas, 72212-4187
Velocity Clinical Research Macon /ID# 266516
Macon, Georgia, 31210-6583
Prime Clinical Research - Mansfield - East Broad Street /ID# 266236
Mansfield, Texas, 76063
South Miami Medical & Research Group Inc. /ID# 249418
Miami, Florida, 33155
Valencia Medical & Research Center /ID# 250452
Miami, Florida, 33165
Palmetto Professional Research /ID# 250875
Miami, Florida, 33172
South Florida Research Ph I-IV /ID# 252350
Miami Springs, Florida, 33166-7225
MNGI Digestive Health, P. A. /ID# 249676
Minneapolis, Minnesota, 55413-2195
Frederick County Pediatrics /ID# 249483
New Market, Maryland, 21774-6154
Rutgers New Jersey Medical School Campus, Doctors Office Center /ID# 250876
Newark, New Jersey, 07103-2425
IPS Research Company /ID# 250822
Oklahoma City, Oklahoma, 73106
Velocity Clinical Research - Phoenix /ID# 266280
Phoenix, Arizona, 85006
Carilion Medical Center /ID# 249790
Roanoke, Virginia, 24014
Medical Ctr for Clin Research /ID# 254386
San Diego, California, 92108
Frontier Clinical Research, LLC - Scottdale /ID# 250656
Scottdale, Pennsylvania, 15683
Frontier Clinical Research - Smithfield /ID# 250657
Smithfield, Pennsylvania, 15478
Coastal Pediatric Research - Summerville /ID# 249423
Summerville, South Carolina, 29486
Tullahoma Pediatrics /ID# 250892
Tullahoma, Tennessee, 37388
Rophe Adult & Pediatric Medicine /ID# 250663
Union City, Georgia, 30291
ClinPoint Trials /ID# 250448
Waxahachie, Texas, 75165-1430
Bulgaria5 sites
UMHAT Kanev /ID# 250815
Rousse, 7002
Acibadem City Clinic Tokuda University Hospital EAD /ID# 251234
Sofia, 1407
Specialized Hospital For Active Treatment Of Children Diseases Prof. Ivan Mitev /ID# 251233
Sofia, 1606
University Hospital Plovdiv /ID# 250814
Tsentar, Plovdiv, 4001
Nova Clinic /ID# 250816
Varna, 9000
United Kingdom3 sites
Doncaster Royal Infirmary /ID# 252080
Armthorpe Road, DN2 5LT
Northern Licolnshire and Goole NHS Foundation Trust /ID# 252007
Grimsby, DN33 2BA
Disc_Barts Health NHS Trust - The Royal London Hospital /ID# 251179
London, Greater London, E1 2ES
Netherlands2 sites
Amsterdam UMC, locatie AMC /ID# 251295
Amsterdam, North Holland, 1105 AZ
Amphia Ziekenhuis /ID# 251698
Breda, North Brabant, 4818 CK
About this study
Official title: 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.
Read more
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.
- Being tested
- Placebo for Linaclotide, Linaclotide
- Keywords
- Functional Constipation (FC), Linaclotide, AGN-182139, Linzess
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo for LinaclotideDrug
Capsule; oral
LinaclotideDrug
Capsule; oral
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Placebo for Linaclotide | Placebo comparator | Participants received placebo for linaclotide orally once daily (QD) for 12 weeks. Receives: Drug: Placebo for Linaclotide |
| Part 1: Linaclotide | Experimental | Participants received 72 µg linaclotide orally once daily (QD) for 12 weeks. Receives: Drug: Linaclotide |
| Part 2: Linaclotide | Experimental | 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. Receives: Drug: Linaclotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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 outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2022
- Study start29 Dec 2022
- Primary completion2 Sep 2025
- Study completion2 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Functional Constipation (FC)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ironwood Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05652205
- Sponsor's protocol ID
- M21-572
- Other IDs
- 2022-501946-31-00
- Status last verified
- Apr 2026
- First submitted
- 2 Dec 2022
- Last updated
- 14 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.