Clinical trial NCT01233869: Bosutinib For Autosomal Dominant Polycystic Kidney Disease
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Of The Safety, Clinical Activity And Pharmacokinetics Of Bosutinib (PF-05208763) Versus Placebo In Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Polycystic Kidney, Autosomal Dominant
Keywords: Bosutinib
Autosomal Dominant Polycystic Kidney Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-11-03
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This purpose of this study is to determine if bosutinib reduces the rate of kidney enlargement in subjects with autosomal dominant polycystic kidney disease (ADPKD) entering the study with a total kidney volume greater than or equal to 750 cc and eGFR greater than or equal to 60 mL/min/1.73m2.


Eligibility criteria: Inclusion Criteria:

* Males and females, 18 to 50 years old at the time of consent.
* Documented diagnosis of ADPKD (PKD-1 or PKD-2 genotypes allowed).
* Total kidney volume ≥ 750 cc, as measured by centrally evaluated MRI.

Exclusion Criteria:

* eGFR \< 60 mL/min/1.73m2.
* Uncontrolled hypertension (defined as systolic blood pressure ≥140 or diastolic blood pressure ≥90 mm Hg).
* Any previous exposure to the bosutinib test article or receipt of other polycystic kidney disease (PKD) therapies.

Primary outcomes:
measure: Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25
timeFrame: Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])
Secondary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination
timeFrame: Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination
measure: Time to First Occurrence or Worsening of Hypertension
timeFrame: Baseline up to Month 25 (end of ITPV)
measure: Time to First Occurrence or Worsening of Back and/or Flank Pain
timeFrame: Baseline up to Month 25 (end of ITPV)
measure: Time to First Occurrence of Gross Hematuria
timeFrame: Baseline up to Month 25 (end of ITPV)
measure: Time to First Occurrence of Proteinuria
timeFrame: Baseline up to Month 25 (end of ITPV)
measure: Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days
timeFrame: Baseline up to Month 25 (end of ITPV)
measure: Number of Participants With High Blood Urea Nitrogen (BUN) Levels
timeFrame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
measure: Number of Participants With High Serum Creatinine (SCr) Levels
timeFrame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
measure: Maximum Observed Plasma Concentration (Cmax) of Bosutinib
timeFrame: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib
timeFrame: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib
timeFrame: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib
timeFrame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Apparent Oral Clearance (CL/F) of Bosutinib
timeFrame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Apparent Volume of Distribution (Vz/F) of Bosutinib
timeFrame: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Terminal Elimination Half-Life (t1/2) of Bosutinib
timeFrame: Day 1 (pre-dose and 1, 3, 5 and 24 hours post-dose), Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Observed Accumulation Ratio (Rac) of Bosutinib
timeFrame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
measure: Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25
timeFrame: Baseline and end of ITPV (Month 25)
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last study drug administration
measure: Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
timeFrame: Baseline up to 30 days after last study drug administration
measure: Number of Participants With Potentially Clinically Significant Vital Signs Findings
timeFrame: Baseline up to 30 days after last study drug administration
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Baseline up to 30 days after last study drug administration
Locations:
city: Phoenix
country: United States
facility: Southwest Kidney Institute, PLC
state: Arizona
city: Tempe
country: United States
facility: Southwest Clinical Research Institute, LLC
state: Arizona
city: Tempe
country: United States
facility: Southwest Kidney Institute, PLC
state: Arizona
city: Sacramento
country: United States
facility: Capital Nephrology Clinical Research
state: California
city: Caldwell
country: United States
facility: Boise Kidney & Hypertension Institute, PLLC
state: Idaho
city: Meridian
country: United States
facility: Boise Kidney & Hypertension Institute, PLLC
state: Idaho
city: Baton Rouge
country: United States
facility: Renal Associates of Baton Rouge
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: New York University - HHC CTSI Clinical Research Center
state: New York
city: Doylestown
country: United States
facility: Doylestown Hospital MRI
state: Pennsylvania
city: Doylestown
country: United States
facility: Doylestown Hospital
state: Pennsylvania
city: Doylestown
country: United States
facility: Nephrology/Hypertension Specialists
state: Pennsylvania
city: San Antonio
country: United States
facility: Renal Associates, PA
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System - Nephrology
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: The Polyclinic
state: Washington
city: Silverdale
country: United States
facility: Renal Remission and Hypertension Clinic
state: Washington
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Hradec Kralove
country: Czech Republic
facility: Klinika gerontologicka a metabolicka
city: Liberec 1
country: Czech Republic
facility: Krajska nemocnice Liberec
city: Nove Mesto na Morave
country: Czech Republic
facility: Nemocnice Nove Mesto na Morave
city: Praha 2
country: Czech Republic
facility: Fakultni poliklinika VFN
city: Praha 2
country: Czech Republic
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 7
country: Czech Republic
facility: Pharmaceutical Research Associates CZ, s.r.o.
city: Budapest
country: Hungary
facility: PRA Magyarorszag Kft. Klinikai Farmakologiai Vizsgalohely
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Szent Imre Korhaz BSZMI Klinikai Farmakologiai Reszlege
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont I.sz.Belgyogyaszati Klinika
city: Cremona
country: Italy
facility: Istituti Ospitalieri di Cremona
city: Foggia
country: Italy
facility: A.O. Universitaria Ospedali Riuniti di Foggia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Department of Internal Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center/Division of Nephrology
city: Seoul
country: Korea, Republic of
facility: Eulji General Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinic, Public Institution, Centre of Nephrology
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican
city: Gdansk
country: Poland
facility: Zaklad Diagnostyki Chorob Serca, II Katedra Kardiologii
city: Gdansk
country: Poland
facility: Klinika Nefrologii, Transplantologii i Chorob Wewnetrznych
city: Grodzisk Mazowiecki
country: Poland
facility: Specjalistyczny Szpital Zachodni im. Jana Pawla II w Grodzisku Mazowieckim
city: Krakow
country: Poland
facility: Krakowskie Centrum Medyczne NZOZ
city: Olsztyn
country: Poland
facility: Klinika Nefrologii, Hipertensjologii i Chorob Wewnetrznych Katedry Chorob Wewnetrznych UWM
city: Olsztyn
country: Poland
facility: Pracownia Echokardiografii, Oddzial Kardiologii
city: Radom
country: Poland
facility: Centrum Medyczne Aesculap
city: Szczecin
country: Poland
facility: Klinika Kardiologii
city: Szczecin
country: Poland
facility: Klinika Nefrologii, Transplantologii i Chorob Wewnetrznych
city: Wolomin
country: Poland
facility: Szpital Powiatowy w Wolominie
city: Wroclaw
country: Poland
facility: SPZOZ Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego
city: Oradea
country: Romania
facility: Spitalul Clinic Municipal Dr. Gavril Curteanu Oradea
state: jud. Bihor
city: Iasi
country: Romania
facility: Spitalul Clinic Dr. C. I. Parhon Iasi
state: jud. Iasi
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni, Centrul de Medicina Interna-Nefrologie
city: Timisoara
country: Romania
facility: SPITALUL CLINIC JUDETEAN DE URGENTA TIMISOARA ,Clinica de Nefrologie
city: Limbova 5
country: Slovakia
facility: Univerzitna nemocnica Bratislava
state: Bratislava
city: Bratislava
country: Slovakia
facility: SUMMIT CLINICAL RESEARCH, s.r.o., Oddelenie internej mediciny a klinickej farmakologie
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Njurmedicin
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
city: Istanbul
country: Turkey
facility: Istanbul University, Istanbul Tip Fakultesi
state: Capa
city: Izmir
country: Turkey
facility: Dokuz Eylul Universitesi Hastanesi Ic Hastaliklari Anabilim Dali
state: Inciralti/ Narlidere
city: Swansea
country: United Kingdom
facility: Morriston Hospital
state: Wales
city: Glasgow
country: United Kingdom
facility: BHF Glasgow Cardiovascular Research Centre, University of Glasgow
city: Leicester
country: United Kingdom
facility: Renal and Urology Directorate, Leicester General Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Tesar V, Ciechanowski K, Pei Y, Barash I, Shannon M, Li R, Williams JH, Levisetti M, Arkin S, Serra A. Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol. 2017 Nov;28(11):3404-3413. doi: 10.1681/ASN.2016111232. Epub 2017 Aug 24.