Clinical Trial: A Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase 1, Safety, Pharmacokinetic, Single Ascending Dose Study of Tesevatinib in Pediatric Subjects With Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Brief Summary: This study evaluates safety and tolerability of a single ascending dose of a tesevatinib liquid formulation administered to pediatric subjects with ARPKD.

Detailed Summary:

This study is a phase 1 clinical trial focused on evaluating safety and tolerability of the Tesevatinib study drug, which is an oral solution at a 15mg/mL concentration.

To determine safety of the tesevatinib liquid formulation in pediatric subjects (age 5-12) with ARPKD, all participants receive active study drug on Day 1 of the study enrollment. To evaluate plasma pharmacokinetics (PK) of the single dose of tesevatinib in the ARPKD pediatric subjects, the blood for PK sampling is drawn on Day 1, 2, and 3 of the study. Tesevatinib dosing will be followed by a PK and a 2-week safety evaluation. After the completion of the safety review subjects may continue onto the next dosing group at the discretion of the investigator and the medical monitor.

There are three dosing arms in this study. Six participants will enroll into first dosing cohort (0.25mg/kg). Participants may be enrolled in two subsequent cohorts with increased dose (0.5mg/kg and 1.0mg/kg), if safety reporting is favorable.

Medical history will be taken at Screening Visit. Echocardiogram will be performed at Screening and Day 14. Subjects will undergo audiology testing, as well as ocular monitoring at Screening and Day 14. Blood will be drawn for a panel of laboratory tests.


Sponsor: Kadmon Corporation, LLC

Current Primary Outcome: Evaluation of the safety and tolerability of a single dose tesevatinib liquid formulation in pediatric participants with ARPKD [ Time Frame: 2 weeks ]

Safety and tolerability endpoints will be measured with the aggregated results of frequency and severity of adverse events and safety assessments (e.g. clinical laboratory tests, physical examinations, vital signs, ECGs, audiology testing, ocular monitoring)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Evaluation of the time to peak of plasma concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD. [ Time Frame: 3 days ]
    Pharmacokinetic parameter Tmax for tesevatinib will be measured as time elapsed till peak concentration.
  • Evaluation of the plasma maximum concentration of a single dose of tesevatinib liquid formulation in pediatric participants with ARPKD. [ Time Frame: 3 days ]
    Pharmacokinetic parameter Cmax for tesevatinib will be used to measure the highest concentration of the drug in plasma.
  • Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-Last hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD. [ Time Frame: 3 days ]
    Pharmacokinetic parameter AUC0-Last for tesevatinib will be measured and summarized by dose.
  • Evaluation of the Area Under the Curve (AUC) of plasma concentration against time 0-24 hours from the single dose administration of tesevatinib liquid formulation in pediatric participants with ARPKD. [ Time Frame: 3 days ]
    Pharmacokinetic parameter AUC0-24 for tesevatinib will be measured and summarized by dose.


Original Secondary Outcome: Same as current

Information By: Kadmon Corporation, LLC

Dates:
Date Received: March 6, 2017
Date Started: May 1, 2017
Date Completion: December 31, 2017
Last Updated: March 31, 2017
Last Verified: March 2017