search
Back to results

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

Primary Purpose

Functional Constipation (FC), Chronic Idiopathic Constipation (CIC)

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Linaclotide
Placebo for Linaclotide
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Functional Constipation (FC) focused on measuring Functional Constipation (FC), Linaclotide, AGN-182139, Linzess

Eligibility Criteria

2 Years - 5 Years (Child)All SexesDoes not accept healthy volunteers

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. 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 Neurodevelopmental disabilities (early-onset, chronic disorders that share the essential feature of a predominant disturbance in the acquisition of cognitive, motor, language, or social skills, which has a significant and continuing impact on the developmental progress of an individual) producing a cognitive delay that precludes comprehension and completion of the daily eDiary or other study-related questionnaires. (Note: participants are excluded if the person who will be completing the daily eDiary or other study-related questionnaires meets this criterion.) 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.

Sites / Locations

  • G & L Research, LLC /ID# 250658Recruiting
  • HealthStar Research of Hot Springs PLLC /ID# 249481Recruiting
  • Applied Research Center of Arkansas /ID# 249764Recruiting
  • Advanced Research Center /ID# 249412Recruiting
  • Medical Ctr for Clin Research /ID# 254386Recruiting
  • Prohealth Research Center /ID# 249420Recruiting
  • KIDZ Medical Services - Hollywood /ID# 250823Recruiting
  • Kissimmee Clinical Research /ID# 252206Recruiting
  • South Florida Research Ph I-IV /ID# 252350Recruiting
  • South Miami Medical & Research Group Inc. /ID# 249418Recruiting
  • Valencia Medical & Research Center /ID# 250452Recruiting
  • Palmetto Professional Research /ID# 250875Recruiting
  • Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 250663Recruiting
  • Michael W. Simon, MD, PSC /ID# 250664Recruiting
  • Virgo Carter Pediatrics /ID# 249483Recruiting
  • Michigan Center of Medical Research /ID# 251088Recruiting
  • MNGI Digestive Health, P. A. /ID# 249676Recruiting
  • Velocity Clinical Research- Hastings Nebraska /ID# 252132Recruiting
  • UH Cleveland Medical Center /ID# 250893Recruiting
  • IPS Research Company /ID# 250822
  • Frontier Clinical Research, LLC - Scottdale /ID# 250656Recruiting
  • Frontier Clinical Research /ID# 250657Recruiting
  • Coastal Pediatric Research - West Ashley B /ID# 249413Recruiting
  • Tribe Clinical Research LLC /ID# 255656Recruiting
  • Coastal Pediatric Research - Summerville /ID# 249423Recruiting
  • Tullahoma Pediatrics /ID# 250892Recruiting
  • Houston Clinical Research Associates /ID# 250779Recruiting
  • ClinPoint Trials /ID# 250448Recruiting
  • Carilion Medical Center /ID# 249790Recruiting
  • Frontier Clinical Research - Kingwood /ID# 251154Recruiting
  • Doncaster Royal Infirmary /ID# 252080Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part 1 Linaclotide

Part 1 Placebo

Part 2 Linaclotide

Arm Description

Participants will receive linaclotide for 12 weeks.

Participants will receive placebo for 12 weeks.

Participants who completed study intervention in Part 1 of this study or the Phase 2 Study LIN-MD-67 will receive 24 weeks of linaclotide exposure.

Outcomes

Primary Outcome Measures

Change from baseline in the spontaneous bowel movement (SBM) frequency rate (SBMs/week) 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.

Secondary Outcome Measures

Change from baseline in stool consistency during the double blind 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.
Change from baseline in straining during the double-blind study intervention period
The caregiver/parent/guardian/LAR will rate and record in an eDiary the amount of straining they observe when the child passes the BM.
Proportion of days with fecal incontinence during the double-blind study intervention period (for participants who have acquired toileting skills during daytime and nighttime or acquired toileting skills during daytime only)
Each day the caregiver/parent/guardian/LAR will record incidents of fecal incontinence in an eDiary.

Full Information

First Posted
December 2, 2022
Last Updated
October 9, 2023
Sponsor
AbbVie
Collaborators
Ironwood Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05652205
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 29, 2022 (Actual)
Primary Completion Date
November 14, 2024 (Anticipated)
Study Completion Date
March 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
Collaborators
Ironwood Pharmaceuticals, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 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 100 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Constipation (FC), Chronic Idiopathic Constipation (CIC)
Keywords
Functional Constipation (FC), Linaclotide, AGN-182139, Linzess

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1 Linaclotide
Arm Type
Experimental
Arm Description
Participants will receive linaclotide for 12 weeks.
Arm Title
Part 1 Placebo
Arm Type
Experimental
Arm Description
Participants will receive placebo for 12 weeks.
Arm Title
Part 2 Linaclotide
Arm Type
Experimental
Arm Description
Participants who completed study intervention in Part 1 of this study or the Phase 2 Study LIN-MD-67 will receive 24 weeks of linaclotide exposure.
Intervention Type
Drug
Intervention Name(s)
Linaclotide
Intervention Description
Capsule; oral
Intervention Type
Drug
Intervention Name(s)
Placebo for Linaclotide
Intervention Description
Capsule; oral
Primary Outcome Measure Information:
Title
Change from baseline in the spontaneous bowel movement (SBM) frequency rate (SBMs/week) during the double-blind study intervention period.
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.
Time Frame
Baseline to Week 12
Secondary Outcome Measure Information:
Title
Change from baseline in stool consistency during the double blind study intervention period
Description
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.
Time Frame
Baseline to Week 12
Title
Change from baseline in straining during the double-blind study intervention period
Description
The caregiver/parent/guardian/LAR will rate and record in an eDiary the amount of straining they observe when the child passes the BM.
Time Frame
Baseline to Week 12
Title
Proportion of days with fecal incontinence during the double-blind study intervention period (for participants who have acquired toileting skills during daytime and nighttime or acquired toileting skills during daytime only)
Description
Each day the caregiver/parent/guardian/LAR will record incidents of fecal incontinence in an eDiary.
Time Frame
Baseline to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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 Neurodevelopmental disabilities (early-onset, chronic disorders that share the essential feature of a predominant disturbance in the acquisition of cognitive, motor, language, or social skills, which has a significant and continuing impact on the developmental progress of an individual) producing a cognitive delay that precludes comprehension and completion of the daily eDiary or other study-related questionnaires. (Note: participants are excluded if the person who will be completing the daily eDiary or other study-related questionnaires meets this criterion.) 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ABBVIE CALL CENTER
Phone
844-663-3742
Email
abbvieclinicaltrials@abbvie.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ABBVIE INC.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
G & L Research, LLC /ID# 250658
City
Foley
State/Province
Alabama
ZIP/Postal Code
36535
Country
United States
Individual Site Status
Recruiting
Facility Name
HealthStar Research of Hot Springs PLLC /ID# 249481
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Individual Site Status
Recruiting
Facility Name
Applied Research Center of Arkansas /ID# 249764
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72212-4187
Country
United States
Individual Site Status
Recruiting
Facility Name
Advanced Research Center /ID# 249412
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical Ctr for Clin Research /ID# 254386
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
Individual Site Status
Recruiting
Facility Name
Prohealth Research Center /ID# 249420
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Individual Site Status
Recruiting
Facility Name
KIDZ Medical Services - Hollywood /ID# 250823
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021-6030
Country
United States
Individual Site Status
Recruiting
Facility Name
Kissimmee Clinical Research /ID# 252206
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Individual Site Status
Recruiting
Facility Name
South Florida Research Ph I-IV /ID# 252350
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166-7225
Country
United States
Individual Site Status
Recruiting
Facility Name
South Miami Medical & Research Group Inc. /ID# 249418
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Individual Site Status
Recruiting
Facility Name
Valencia Medical & Research Center /ID# 250452
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Individual Site Status
Recruiting
Facility Name
Palmetto Professional Research /ID# 250875
City
Miami
State/Province
Florida
ZIP/Postal Code
33172
Country
United States
Individual Site Status
Recruiting
Facility Name
Rophe Adult and Pediatric Medicine/SKYCRNG /ID# 250663
City
Union City
State/Province
Georgia
ZIP/Postal Code
30291
Country
United States
Individual Site Status
Recruiting
Facility Name
Michael W. Simon, MD, PSC /ID# 250664
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40517
Country
United States
Individual Site Status
Recruiting
Facility Name
Virgo Carter Pediatrics /ID# 249483
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20910
Country
United States
Individual Site Status
Recruiting
Facility Name
Michigan Center of Medical Research /ID# 251088
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Individual Site Status
Recruiting
Facility Name
MNGI Digestive Health, P. A. /ID# 249676
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55413-2195
Country
United States
Individual Site Status
Recruiting
Facility Name
Velocity Clinical Research- Hastings Nebraska /ID# 252132
City
Hastings
State/Province
Nebraska
ZIP/Postal Code
68901-2640
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Coordinator
Phone
402-407-2800
Facility Name
UH Cleveland Medical Center /ID# 250893
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
IPS Research Company /ID# 250822
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73106
Country
United States
Individual Site Status
Completed
Facility Name
Frontier Clinical Research, LLC - Scottdale /ID# 250656
City
Scottdale
State/Province
Pennsylvania
ZIP/Postal Code
15683
Country
United States
Individual Site Status
Recruiting
Facility Name
Frontier Clinical Research /ID# 250657
City
Smithfield
State/Province
Pennsylvania
ZIP/Postal Code
15478
Country
United States
Individual Site Status
Recruiting
Facility Name
Coastal Pediatric Research - West Ashley B /ID# 249413
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414
Country
United States
Individual Site Status
Recruiting
Facility Name
Tribe Clinical Research LLC /ID# 255656
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29607-4021
Country
United States
Individual Site Status
Recruiting
Facility Name
Coastal Pediatric Research - Summerville /ID# 249423
City
Summerville
State/Province
South Carolina
ZIP/Postal Code
29486
Country
United States
Individual Site Status
Recruiting
Facility Name
Tullahoma Pediatrics /ID# 250892
City
Tullahoma
State/Province
Tennessee
ZIP/Postal Code
37388
Country
United States
Individual Site Status
Recruiting
Facility Name
Houston Clinical Research Associates /ID# 250779
City
Houston
State/Province
Texas
ZIP/Postal Code
77090-2633
Country
United States
Individual Site Status
Recruiting
Facility Name
ClinPoint Trials /ID# 250448
City
Waxahachie
State/Province
Texas
ZIP/Postal Code
75165-1430
Country
United States
Individual Site Status
Recruiting
Facility Name
Carilion Medical Center /ID# 249790
City
Roanoke
State/Province
Virginia
ZIP/Postal Code
24014
Country
United States
Individual Site Status
Recruiting
Facility Name
Frontier Clinical Research - Kingwood /ID# 251154
City
Kingwood
State/Province
West Virginia
ZIP/Postal Code
26537-9797
Country
United States
Individual Site Status
Recruiting
Facility Name
Doncaster Royal Infirmary /ID# 252080
City
Armthorpe Road
ZIP/Postal Code
DN2 5LT
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
IPD Sharing Time Frame
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
IPD Sharing Access Criteria
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
IPD Sharing URL
https://vivli.org/ourmember/abbvie/
Links:
URL
https://www.abbvieclinicaltrials.com/study/?id=M21-572
Description
This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses.

Learn more about this trial

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

We'll reach out to this number within 24 hrs