A Safety, Pharmacokinetic & Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease
Condition: Polycystic Kidney, Autosomal Dominant
MeSH terms: Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The primary objective of this study Phase 1b was to determine the safety, plasma
      pharmacokinetics, and maximum tolerated dose (MTD) of tesevatinib when administered to
      participants with autosomal dominant polycystic kidney disease (ADPKD).

      The primary objective of this study Phase 2a was to evaluate the annualized change in
      glomerular filtration rate (GFR) in participants with ADPKD when treated with tesevatinib.
    

Detailed description: 
      Phase 1b:

        -  Primary objective was to determine the safety of tesevatinib.

        -  Dosing was for 28 days daily. After the 28-day treatment period, participants would, at
           the discretion of the investigator, continue to receive study treatment for 24 months
           from their first dose or until the development of unacceptable toxicity, noncompliance,
           or withdrawal of consent by the participant, or investigator decision. Participants
           might continue beyond 24 months at the discretion of the investigator after consultation
           with the medical monitor.

        -  All participants received active tesevatinib study drug.

        -  Tesevatinib is an oral once daily tablet. Tablets were 50 milligrams (mg), 100 mg and
           150 mg in strength. Participants were enrolled into three sequential dosing cohort
           levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b had their dose increased or
           decreased to the maximum tolerated dose (MTD).

        -  Study participants had magnetic resonance imaging (MRI) of the abdomen (kidneys) at
           Screening and 6 months thereafter to explore effects of KD019.

        -  Echocardiogram was performed at Screening, Day 28, months 3 and 6 and every 6 months
           thereafter.

      Phase 2a:

        -  Primary objective was to compare the annualized change in GFR in participants with ADPKD
           when treated with tesevatinib.

        -  Two alternate dosing schedules were explored to determine if they were more tolerable
           than daily dosing when used chronically in participants with ADPKD.

        -  Participants received study treatment for 24 months from their first dose or until the
           development of unacceptable toxicity, noncompliance, or withdrawal of consent by the
           participant, or investigator decision. Participants continued beyond 24 months at the
           discretion of the investigator after consultation with the sponsor.

        -  All participants received active tesevatinib study drug.

        -  Tablets were 50 mg, 100 mg, and 150 mg in strength.

        -  Study participants had MRI of the abdomen (kidneys) at Screening and Month 6 visit and
           every 6 months after to explore effects of tesevatinib.

        -  Echocardiogram was performed at Screening, Day 28, and Months 3 and 6 and 6 months
           thereafter.
    

Intervention name(s): Tesevatinib
Intervention type(s): Drug
Intervention description(s): Pharmaceutical form: Tablets Route of administration: Oral
Other intervention name(s): XL647 and KD019
Intervention MeSH terms: XL647
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment