Clinical Trial: A Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease

Brief Summary: The primary objective of this study is to determine the safety, plasma pharmacokinetics, and maximum tolerated dose (MTD) of KD019 when administered to subjects with ADPKD.

Detailed Summary:

Phase 1:

  • Primary purpose is to determine the safety of KD019.
  • Dosing is for 28 days daily. After the 28-day treatment period, subjects will, 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 subject, or investigator decision. Subjects may continue beyond 24 months at the discretion of the investigator after consultation with the medical monitor.
  • All participants receive active KD019 study drug.
  • KD019 is an oral once daily tablet. Tablets are 50 mg, 100 mg and 150 mg in strength. Participants will enroll into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b will have their dose increased or decreased to the MTD.
  • Study participants will have MRI of the abdomen (kidneys) at Screening and 6 months thereafter to explore effects of KD019.
  • Echocardiogram will be performed at Screening, Day 28, months 3 and 6 and every 6 months thereafter.

Phase 2:

  • Primary purpose is to compare the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019.
  • Two alternate dosing schedules will be explored to determine if they are more tolerable than daily dosing when used chronically in subjects with ADPKD.
  • Subjects will receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or wi
    Sponsor: Kadmon Corporation, LLC

    Current Primary Outcome:

    • Safety, Plasma Pharmacokinetics and Maximum Tolerated Dose of KD019 [ Time Frame: 24 months ]
      Phase 1b: Determine the safety, plasma pharmacokinetics and maximum tolerated dose (MTD) of KD019 when administered in subjects with ADPKD
    • Glomerular Filtration Rate [ Time Frame: 24 months ]
      Phase 2a: Evaluate the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019


    Original Primary Outcome:

    • Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
    • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
      Measuring the area under the curve (AUC)
    • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
      Measuring the half-life(T1/2),
    • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
      Measuring Peak plasma concentration (Cmax)
    • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
      Measuring time to maximum concentration (Tmax)
    • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ]
      Measuring drug clearance (CL)


    Current Secondary Outcome:

    • Total Kidney Volume [ Time Frame: 24 months ]
      Evaluate the annualized percent change from baseline in total kidney volume (TKV) in subjects with ADPKD treated with KD019
    • Serum Creatinine [ Time Frame: 24 months ]
      Evaluate the annualized change from baseline in the reciprocal of serum creatinine in subjects with ADPKD treated with KD019
    • Safety, Tolerability, and Pharmacokinetics of an Alternative Dosing Schedule [ Time Frame: 24 months ]
      Evaluate the safety profile, tolerability, and pharmacokinetics in subjects with ADPKD treated with KD019 on an alternative dosing schedule. Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD.


    Original Secondary Outcome: Exploratory measures of efficacy will be performed. [ Time Frame: an expected average of approximately 8 months ]

    Efficacy will be explored with regard to the effect of KD019 on eGFR.


    Information By: Kadmon Corporation, LLC

    Dates:
    Date Received: March 9, 2012
    Date Started: September 2012
    Date Completion:
    Last Updated: February 3, 2017
    Last Verified: June 2016