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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Kadmon Corporation, LLC
Sponsor:
Information provided by (Responsible Party):
Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:
NCT01559363
First received: March 9, 2012
Last updated: November 17, 2014
Last verified: November 2014

March 9, 2012
November 17, 2014
September 2012
January 2017   (final data collection date for primary outcome measure)
  • Safety, Plasma Pharmacokinetics and Maximum Tolerated Dose of KD019 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    Phase 2a: Evaluate the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019
  • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]
    Measuring Peak plasma concentration (Cmax)
  • 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 ] [ Designated as safety issue: Yes ]
  • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Measuring drug clearance (CL)
  • Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Measuring the half-life(T1/2),
Complete list of historical versions of study NCT01559363 on ClinicalTrials.gov Archive Site
  • Total Kidney Volume [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.
Exploratory measures of efficacy will be performed. [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]
Efficacy will be explored with regard to the effect of KD019 on eGFR.
Not Provided
Not Provided
 
A Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease

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.

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.
  • KD019 will be either dosed on Monday, Wednesday and Friday of each week or Monday and Thursday of each week. Subjects will 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 sponsor.
  • All participants receive active KD019 study drug.
  • KD019 is an oral tablet dosed on Monday, Wednesday and Friday or Monday and Thursday of every week. Tablets are 50 mg, 100 mg, and 150 mg in strength.
  • Study participants will have MRI of the abdomen (kidneys) at Screening and Month 6 visit and every 6 months after to explore effects of KD019.
  • Echocardiogram will be performed at Screening, Day 28, and Months 3 and 6 and 6 months thereafter.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Polycystic Kidney, Autosomal Dominant
Drug: KD019
Other Name: XL647
  • Experimental: Cohort 1
    One 50mg KD019 tablet per day for 28 days and up to 24 months
    Intervention: Drug: KD019
  • Experimental: Cohort 2
    Two 50mg KD019 tablets per day for 28 days and up to 24 months
    Intervention: Drug: KD019
  • Experimental: Cohort 3
    Three 50mg KD019 tablets per day for 28 days and up to 24 months
    Intervention: Drug: KD019
  • Experimental: Phase 2a Monday, Wednesday, Friday
    An alternate dosing schedule of dosing on Monday, Wednesday and Friday of each week 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
    Intervention: Drug: KD019
  • Experimental: Phase 2a Monday and Thursday
    An alternate dosing schedule of dosing on Monday and Thursday of each week 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
    Intervention: Drug: KD019
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
55
Not Provided
January 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The subject has a confirmed diagnosis of ADPKD.
  • The subject has a GFR ≥ 50 mL/min/1.73 m2.
  • Cysts must be at least 1 cm in size.
  • Adequate bone marrow, kidney, and liver function.
  • Must agree to use two forms of birth control for those of child bearing potential
  • Normal amylase and lipase levels

Exclusion Criteria:

  • The subject has had a previous partial or total nephrectomy.
  • The subject has tuberous sclerosis, Hippel-Lindau disease, or acquired cystic disease.
  • The subject has congenital absence of one kidney and/or need for dialysis.
  • Presence of renal or hepatic calculi (stones) causing symptoms.
  • The subject has received any investigational therapy within 30 days prior to study entry.
  • Active treatment (within 4 weeks of study entry) for urinary tract infection.
  • Subject is known to be immunocompromised
  • Subject is pregnant or nursing
  • History of pericardial effusion or presence of pericardial effusion on screening echocardiogram
  • Uncontrolled hypertension
  • History of pancreatitis or has known risk factors for pancreatitis
Both
18 Years to 55 Years
No
United States
 
NCT01559363
KD019-101
No
Kadmon Corporation, LLC
Kadmon Corporation, LLC
Not Provided
Not Provided
Kadmon Corporation, LLC
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP