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

Purpose

The primary objective of this study is to determine the safety, tolerability, and plasma pharmacokinetics of KD019 when administered to subjects with ADPKD.

Condition	Intervention	Phase
Polycystic Kidney, Autosomal Dominant	Drug: KD019	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1b/2a, Safety, Pharmacokinetic and Dose-Escalation Study of KD019 in Subjects With Autosomal Dominant Polycystic Kidney Disease

Resource links provided by NLM:

Genetics Home Reference related topics: polycystic kidney disease

U.S. FDA Resources

Further study details as provided by Kadmon Corporation, LLC:

Primary Outcome Measures:

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)

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	110
Study Start Date:	September 2012
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 One 50mg KD019 tablet per day for 28 days and up to 6 months	Drug: KD019 Other Name: XL647
Experimental: Cohort 2 Two 50mg KD019 tablets per day for 28 days and up to 6 months	Drug: KD019 Other Name: XL647
Experimental: Cohort 3 Three 50mg KD019 tablets per day for 28 days and up to 6 months	Drug: KD019 Other Name: XL647
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	Drug: KD019 Other Name: XL647

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.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559363

Locations

United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lisa Bungum 507-266-4616 Bungum.Lisa2@mayo.edu
United States, New York
New York University School of Medicine	Recruiting
New York, New York, United States, 10016
Contact: Casey Santana 212-263-6411 casey.santana@nyumc.org

Sponsors and Collaborators

Kadmon Corporation, LLC

More Information

No publications provided

Responsible Party:	Kadmon Corporation, LLC
ClinicalTrials.gov Identifier:	NCT01559363 History of Changes
Other Study ID Numbers:	KD019-101
Study First Received:	March 9, 2012
Last Updated:	November 1, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic

ClinicalTrials.gov processed this record on May 16, 2013