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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

Primary Purpose

Functional Constipation

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Linaclotide
Placebo
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Functional Constipation focused on measuring Linaclotide, pediatric functional constipation, Linzess

Eligibility Criteria

6 Months - 23 Months (Child)All SexesDoes not accept healthy volunteers

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 modified 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 volitional 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 modified 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 Neurodevelopmental disabilities of the LAR/Parent/Guardian/Caregiver who will be completing the eDiary (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. 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)

Sites / Locations

  • HealthStar Research of Hot Springs PLLC /ID# 251553Recruiting
  • Advanced Research Center /ID# 248763Recruiting
  • Prohealth Research Center /ID# 248696Recruiting
  • South Miami Medical & Research Group Inc. /ID# 248765Recruiting
  • Virgo Carter Pediatrics /ID# 251555Recruiting
  • Coastal Pediatric Research - West Ashley B /ID# 248693Recruiting
  • Coastal Pediatric Research - Summerville /ID# 253534Recruiting
  • ClinPoint Trials /ID# 251534Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1, Linaclotide Dose A

Part 1, Linaclotide Dose B

Part 1, Linaclotide Dose C

Part 2, Linaclotide

Part 2, Placebo

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.
Change from baseline in straining during the 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.
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.

Secondary Outcome Measures

Full Information

First Posted
February 27, 2023
Last Updated
October 19, 2023
Sponsor
AbbVie
Collaborators
Ironwood Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05760313
Brief Title
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
Official Title
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).
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2023 (Actual)
Primary Completion Date
April 9, 2024 (Anticipated)
Study Completion Date
December 20, 2024 (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 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. Approximately 30 pediatric participants 6 months to less than 2 years of age with FC will be enrolled in the study at about 25 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Constipation
Keywords
Linaclotide, pediatric functional constipation, Linzess

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Part 1, Linaclotide Dose A
Arm Type
Experimental
Arm Description
Linaclotide Dose A capsules, mixed with water and administered orally, once daily for 4 weeks
Arm Title
Part 1, Linaclotide Dose B
Arm Type
Experimental
Arm Description
Linaclotide Dose B capsules, mixed with water and administered orally, once daily for 4 weeks
Arm Title
Part 1, Linaclotide Dose C
Arm Type
Experimental
Arm Description
Linaclotide Dose C capsules, mixed with water and administered orally, once daily for 4 weeks
Arm Title
Part 2, Linaclotide
Arm Type
Experimental
Arm Description
Participants will receive Linaclotide capsules mixed with water and administered orally in Part 2 for 4 weeks.
Arm Title
Part 2, Placebo
Arm Type
Experimental
Arm Description
Participants will receive placebo capsules mixed with water and administered orally in Part 2 for 4 weeks.
Intervention Type
Drug
Intervention Name(s)
Linaclotide
Other Intervention Name(s)
Linzess
Intervention Description
Capsule; oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Capsule; oral
Primary Outcome Measure Information:
Title
Change from baseline in overall Spontaneous Bowel Movement (SBM) frequency rate (SBMs/week) during the 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 4-week SBM frequency rate.
Time Frame
Baseline to Week 4
Title
Change from baseline in stool consistency (Bristol Stool Form Scale) during the 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 4
Title
Change from baseline in straining during the 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 4
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Up to Week 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
23 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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 modified 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 volitional 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 modified 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 Neurodevelopmental disabilities of the LAR/Parent/Guardian/Caregiver who will be completing the eDiary (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. 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)
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
HealthStar Research of Hot Springs PLLC /ID# 251553
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Individual Site Status
Recruiting
Facility Name
Advanced Research Center /ID# 248763
City
Anaheim
State/Province
California
ZIP/Postal Code
92805
Country
United States
Individual Site Status
Recruiting
Facility Name
Prohealth Research Center /ID# 248696
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Individual Site Status
Recruiting
Facility Name
South Miami Medical & Research Group Inc. /ID# 248765
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Individual Site Status
Recruiting
Facility Name
Virgo Carter Pediatrics /ID# 251555
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20910
Country
United States
Individual Site Status
Recruiting
Facility Name
Coastal Pediatric Research - West Ashley B /ID# 248693
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Coordinator
Phone
844-663-3742
Facility Name
Coastal Pediatric Research - Summerville /ID# 253534
City
Summerville
State/Province
South Carolina
ZIP/Postal Code
29486
Country
United States
Individual Site Status
Recruiting
Facility Name
ClinPoint Trials /ID# 251534
City
Waxahachie
State/Province
Texas
ZIP/Postal Code
75165-1430
Country
United States
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
http://www.abbvieclinicaltrials.com/study/?id=M21-862
Description
Related Info

Learn more about this trial

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

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