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

This study is currently recruiting participants.

Verified November 2012 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 1, 2012

Last verified: November 2012

History of Changes

Tracking Information
First Received Date ^ICMJE	March 9, 2012
Last Updated Date	November 1, 2012
Start Date ^ICMJE	September 2012
Estimated Primary Completion Date	June 2014 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: March 19, 2012)	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 ] Determine the maximum tolerated dose (MTD) of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ] Measurement of glomerular filtration rate in subjects with ADPKD when treated with KD019 [ Time Frame: an expected average of approximately 12 months ] [ Designated as safety issue: No ] Compare the annualized change in glomerular filtration rate (GFR) 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) 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)
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01559363 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: November 1, 2012)	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. Measurement of Total kidney volume in subjects with ADPKD when treated with KD019 [ Time Frame: an expected average of approximately 12 months ] [ Designated as safety issue: No ] Annualized percent change from baseline in total kidney volume (TKV) Measurement of total cyst volume in subjects with ADPKD wehn treated with KD019 [ Time Frame: an expected average of approximately 12 months ] [ Designated as safety issue: No ] Annualized percent change from baseline in total cyst volume (TCV) Measurement of serum creatinine in subjects with ADPKD wehn treated with KD019 [ Time Frame: an expected average of approximately 12 months ] [ Designated as safety issue: No ] Annualized change from baseline in the reciprocal of serum creatinine Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD at the maximum tolerated dose [ Time Frame: an expected average of approximately 12 month ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures ^ICMJE (submitted: March 19, 2012)	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.
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	A Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease
Official Title ^ICMJE	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, tolerability, and plasma pharmacokinetics of KD019 when administered to subjects with ADPKD.
Detailed Description	Phase 1: Primary purpose is to determine the safety of KD019. 28-days, daily dosing study with option to continue through six months of KD019 dosing. All participants receive active KD019 study drug. KD019 is an oral once daily tablet. Tablets are 50 mg in strength. Participants will enroll into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg. Study participants will have MRI of the abdomen (kidneys) at Screening and Month 6 visit to explore effects of KD019. Echocardiogram will be performed at Screening, Day 28, and Months 2-6 if option for continuation past Day 28 is accepted. Phase 2: Primary purpose is to compare the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019. Dosing is 28-days of daily. Subjects may, if they desire and at the discretion of the investigator, continue to receive study treatment for 12 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision. All participants receive active KD019 study drug. KD019 is an oral once daily tablet. Tablets are 50 mg in strength. Participants in Phase 2 will be given the maximum tolerated dose. 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 2-6 if option for continuation past Day 28 is accepted.
Study Type ^ICMJE	Interventional
Study Phase	Phase 1 Phase 2
Study Design ^ICMJE	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Condition ^ICMJE	Polycystic Kidney, Autosomal Dominant
Intervention ^ICMJE	Drug: KD019 Other Name: XL647
Study Arm (s)	Experimental: Cohort 1 One 50mg KD019 tablet per day for 28 days and up to 6 months Intervention: Drug: KD019 Experimental: Cohort 2 Two 50mg KD019 tablets per day for 28 days and up to 6 months Intervention: Drug: KD019 Experimental: Cohort 3 Three 50mg KD019 tablets per day for 28 days and up to 6 months Intervention: Drug: KD019 Experimental: Phase 2a Maximum tolerated dose per day for 28 days 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
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Recruiting
Estimated Enrollment ^ICMJE	110
Completion Date	Not Provided
Estimated Primary Completion Date	June 2014 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	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. 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.
Gender	Both
Ages	18 Years to 50 Years
Accepts Healthy Volunteers	No
Contacts ^ICMJE	Not Provided
Location Countries ^ICMJE	United States

Administrative Information
NCT Number ^ICMJE	NCT01559363
Other Study ID Numbers ^ICMJE	KD019-101
Has Data Monitoring Committee	No
Responsible Party	Kadmon Corporation, LLC
Study Sponsor ^ICMJE	Kadmon Corporation, LLC
Collaborators ^ICMJE	Not Provided
Investigators ^ICMJE	Not Provided
Information Provided By	Kadmon Corporation, LLC
Verification Date	November 2012
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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