Maralixibat in Patients With Cystic Fibrosis and Constipation

Maralixibat in Patients With Cystic Fibrosis and Constipation, A Within-Subjects Pilot Study

Chronic constipation is common in children with cystic fibrosis (CF), likely due to impaired chloride channel function that reduces intestinal secretions. Standard osmotic laxatives often provide inadequate relief in this population.

Maralixibat is an ileal bile acid transporter inhibitor (IBATi) that increases the amount of bile acids reaching the colon. Bile acids can enhance intestinal secretion, reduce transit time, and soften stool. This study will evaluate whether Maralixibat improves stool consistency in children with CF who experience constipation.

We will enroll 20 children with CF and constipation, defined as a Bristol Stool Scale score <4 for at least one week while on a stable laxative regimen. Each participant will receive Maralixibat for two weeks in addition to their usual laxatives. Families will record stool consistency and ease of defecation before and during treatment.

The primary objective is to determine whether Maralixibat improves stool consistency to a Bristol Stool Scale score >4. The secondary objective is to assess changes in ease of defecation using standardized questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis; Constipation Chronic Idiopathic
• Intervention / Treatment: Drug: Maralixibat 9.5 MG/ML [Livmarli]

Detailed Description

Constipation is a frequent gastrointestinal complication in children with cystic fibrosis (CF). Impaired CFTR-mediated chloride and water secretion leads to dehydrated intestinal contents, slowed transit, and difficulty with stool passage. Despite routine use of osmotic laxatives, many children with CF continue to experience hard stools, abdominal discomfort, and incomplete evacuation, highlighting the need for alternative therapeutic approaches.

This study will evaluate the effect of Maralixibat on stool consistency and ease of defecation in children with CF who meet criteria for constipation while on a stable laxative regimen. The study uses a within-subjects design in which each participant serves as their own control. After a baseline observation period, participants will receive Maralixibat for two weeks in addition to their existing constipation management. Families will record stool characteristics and defecation symptoms using standardized tools provided by the study team.

Changes in stool consistency and ease of defecation will be assessed by comparing pre-treatment and treatment-period data. The study is designed to generate preliminary evidence regarding the potential utility of IBAT inhibition as an adjunctive therapy for constipation in pediatric CF patients and to inform the feasibility and design of future controlled trials.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jaya Punati, MD; Phone Number: 3233615924; Email: jpunati@chla.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital Los Angeles
      • Contact: Jaya Punati, MD; Email: jpunati@chla.usc.edu
      • Principal Investigator: Jaya Punati, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Ages 1 to 18 years.
• Proven diagnosis of Cystic Fibrosis confirmed by genetic testing or sweat chloride testing.
• Proven diagnosis of chronic constipation, defined as a Bristol Stool Scale (BSS) score <3 while on a stable conventional constipation therapy regimen.
• Stable conventional constipation medication regimen (no medication changes or dose adjustments) for at least 4 weeks prior to enrollment. Conventional therapy may include stool softeners, stimulant laxatives, or dietary interventions.

Exclusion Criteria

• Uncontrolled fat-soluble vitamin deficiency (Vitamin A, D, E, or K).
• Changes to conventional constipation medication regimen within 4 weeks prior to initiation of Maralixibat.
• Adequately treated chronic constipation, defined as a Bristol Stool Scale (BSS) score >3 on the current regimen.
• Known allergy or sensitivity to Maralixibat or any study-related ingredients.
• Inability or unwillingness of the participant or legal guardian/representative to provide written informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: treatment arm; within - subjects study	Drug: Maralixibat 9.5 MG/ML [Livmarli]; Within Study subjects receiving 2 weeks of treatment with Maralixibat 9.5 MG/ML [Livmarli] and compare to baseline treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Stool Consistency Measured by the Bristol Stool Scale	Constipation is defined as a Bristol Stool Scale (BSS) score of 1-3. The primary endpoint is the proportion of participants who demonstrate improvement in stool consistency, defined as either an increase of at least 1 point on the BSS from baseline or achieving a post-treatment BSS score greater than 3. The Bristol Stool Scale (BSS) is a clinical tool used to classify stool form into seven categories, ranging from very hard to entirely liquid. It helps quantify stool consistency and is commonly used in constipation and gastrointestinal studies.	baseline to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in subjective scoring in ease of stooling with the addition of Maralixibat to a conventional constipation medication regimen via subjective questionnaire.	Maralixibat inhibits baseline absorption which in turn results in looser stools by osmosis. We will use a questionnaire to record subjective report of ease of stooling by patients from baseline prior to intervention using a Likert score of 1-5; - cannot stool; - Difficulty stooling; - neither easy nor difficult; - Easier stooling with medication; - No issues with stooling	Baseline - 3 weeks

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles
• Investigators: Principal Investigator: Jaya Punati, MD, Children's Hospital Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Chronic Constipation; Maralixibiat; Bristol Stool
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; maralixibat
• Other Study ID Numbers: CHLA-23-00352

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No