IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease

NCT06324396 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: STUDY000029745T32HD069038
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, prospective, investigation to quantify the effects liver congestion and fibrosis has on hepatic drug metabolism and transport in children, adolescents, and young adults with Fontan circulation.

Conditions

Fontan Circulation

Keywords

Fontan; FALD

Outcome Measures

Primary Outcomes (2)

• Sildenafil concentration as measured by area under the curve (AUC)

  Area under the time-exposure curve (AUC 0-n) for sildenafil as determinants of the dose-exposure relationship.

  2 years

• Pravastatin concentration as measured by area under the curve (AUC)

  Area under the time-exposure curve (AUC 0-n) for pravastatin as determinants of the dose-exposure relationship.

  2 years

Study Arms (1)

Assessment Arm

EXPERIMENTAL

Assessment group will receive a single dose of oral sildenafil and oral pravastatin.

Drug: Sildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg); Drug: Pravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years)

Interventions

Sildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg) DRUG

A single oral dose of sildenafil will be administered to all study subjects.

Assessment Arm

Pravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years) DRUG

A single oral dose of pravastatin will be administered to all study subjects.

Assessment Arm

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 8 years
• Status Post Fontan Completion
• Ability to provide informed permission-assent (\<18 years) or consent (≥18 years)
• Fasting overnight (\~8 hours)

You may not qualify if:

• Pregnancy
• Non-fasting
• Non-removable metal in body or where magnetic resonance imaging (MRI) is considered unsafe
• Sildenafil and/or Pravastatin therapy within last 2 months
• History of underlying or laboratory evidence of underlying intestinal, metabolic, autoimmune, renal disease that can alter Sildenafil and Pravastatin disposition (absorption, metabolism, distribution, or clearance)
• Pharmacotherapy that interacts with Sildenafil (cytochrome P450 3A4 and P450 3A5 (CYP3A4/5) inducers/inhibitors) and/or Pravastatin (organic anion transporting polypeptide (OATP1B1) inducers/inhibitors)
• Inability to swallow a tablet
• \>5X the age-specific upper limit of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total and conjugated bilirubin
• Diarrhea in the last 24 hours \*History of solid organ transplantation

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• Indiana Clinical and Translational Sciences Institute: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

RECRUITING

MeSH Terms

Interventions

Sildenafil Citrate; Tablets; Pravastatin; Glycation End Products, Advanced

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dosage Forms; Pharmaceutical Preparations; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glycoconjugates; Carbohydrates; Toxins, Biological; Biological Factors

Study Officials

• Jonathan Wagner, DO

  Children's Mercy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonthan Wagner, DO

CONTACT

816-731-7240; jbwagner@cmh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation

Model Details: This is a single center, open-label, prospective, investigation to quantify the effects of liver congestion and fibrosis has on hepatic statin transport (SA1) and response (SA2) in children, adolescents, and young adults with Fontan circulation.

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: March 22, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

US (1)