Bosutinib For Autosomal Dominant Polycystic Kidney Disease

Phase 2

Completed

Conditions: Polycystic Kidney, Autosomal Dominant

Interventions: Drug: Placebo
Drug: Bosutinib

Registration Number: NCT01233869

Lead Sponsor: Pfizer

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 172

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort C	Placebo	-
Cohort B	Bosutinib	-
Cohort A	Bosutinib	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25	Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])	TKV was measured by centrally evaluated Magnetic Resonance Imaging (MRI).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination	Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination	eGFR was centrally evaluated. Glomerular filtration rate (GFR) is an index of kidney function that describes the flow of filtered fluid through the kidney. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Month 25 is the end of the ITPV.
Time to First Occurrence or Worsening of Hypertension	Baseline up to Month 25 (end of ITPV)	The time to first occurrence or worsening of hypertension was observed (defined as the need for increased dose of or need for additional anti-hypertensive medication). The numbers presented correspond to the very first occurrence or worsening of hypertension in that treatment group.
Time to First Occurrence or Worsening of Back and/or Flank Pain	Baseline up to Month 25 (end of ITPV)	The time to first occurrence or worsening of back and/or flank pain was observed (defined as initial onset of polycystic kidney disease \[PKD\]-related chronic back and/or flank pain; initiation of pain medication treatment for PKD-related chronic back and/or flank pain; addition of a pain medicine for treatment of PKD-related chronic back and/or flank pain; increase in dose of pain medication for treatment of PKD-related chronic back and/or flank pain). The numbers presented correspond to the very first occurrence or worsening of back and/or flank pain in that treatment group.
Time to First Occurrence of Gross Hematuria	Baseline up to Month 25 (end of ITPV)	Gross hematuria is the presence of blood in the urine (defined as pink, red, or cola-colored urine due to the presence of red blood cells). The numbers presented correspond to the very first occurrence of gross hematuria in that treatment group.
Time to First Occurrence of Proteinuria	Baseline up to Month 25 (end of ITPV)	Proteinuria is the presence of an excess of serum proteins in the urine, which may be an early sign of kidney disease. The numbers presented correspond to the very first occurrence of proteinuria in that treatment group.
Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days	Baseline up to Month 25 (end of ITPV)	ESRD is when the kidneys permanently fail to work at a level needed for daily life. No participants developed ESRD during the treatment period, therefore the analysis of the onset of ESRD requiring ≥56 days of dialysis was not performed.
Number of Participants With High Blood Urea Nitrogen (BUN) Levels	Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)	A BUN test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high BUN level (\>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.
Number of Participants With High Serum Creatinine (SCr) Levels	Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)	A SCr test can reveal how well the kidneys are working by measuring the amount of urea nitrogen in the blood. A high SCr level (\>1.3 times the upper limit of normal) may suggest that the kidneys are not working properly. Month 25 is the end of the ITPV.
Maximum Observed Plasma Concentration (Cmax) of Bosutinib	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)
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib	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)
Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib	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)	Area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau=24 hours.
Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib	Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Apparent Oral Clearance (CL/F) of Bosutinib	Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Volume of Distribution (Vz/F) of Bosutinib	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)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Terminal Elimination Half-Life (t1/2) of Bosutinib	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)	t1/2 is the time measured for the plasma concentration to decrease by one half.
Observed Accumulation Ratio (Rac) of Bosutinib	Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)	Observed accumulation ratio (Rac) was calculated as AUC from time 0 to 24 hours (Day 15) divided by AUC from time 0 to 24 hours (Day 1).
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25	Baseline and end of ITPV (Month 25)	The KDQoL-36 is a 36-item questionnaire on kidney disease-specific measure of patient-reported quality of life with 5 subscales: physical and mental functioning (items 1-12); burden of kidney disease subscale (items 13-16); symptoms and problems (items 17-28); effects of kidney disease on daily life subscale (items 29-36). The raw scores are transformed linearly to a range of 0 to 100, with higher scores indicating better quality of life.

Trial Locations

Locations (64): Toronto General Hospital
🇨🇦
Toronto, Ontario, Canada
Southwest Kidney Institute, PLC
🇺🇸
Tempe, Arizona, United States
Capital Nephrology Clinical Research
🇺🇸
Sacramento, California, United States
Washington University School of Medicine
🇺🇸
St. Louis, Missouri, United States
New York University - HHC CTSI Clinical Research Center
🇺🇸
New York, New York, United States
Doylestown Hospital
🇺🇸
Doylestown, Pennsylvania, United States
Nephrology/Hypertension Specialists
🇺🇸
Doylestown, Pennsylvania, United States
Renal Associates, PA
🇺🇸
San Antonio, Texas, United States
San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
🇺🇸
San Antonio, Texas, United States
University of Virginia Health System - Nephrology
🇺🇸
Charlottesville, Virginia, United States
University of Virginia Health System
🇺🇸
Charlottesville, Virginia, United States
Renal Remission and Hypertension Clinic
🇺🇸
Silverdale, Washington, United States
Hopital du Sacre-Coeur de Montreal
🇨🇦
Montreal, Quebec, Canada
Krajska nemocnice Liberec
🇨🇿
Liberec 1, Czech Republic
Vseobecna fakultni nemocnice v Praze
🇨🇿
Praha 2, Czech Republic
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont I.sz.Belgyogyaszati Klinika
🇭🇺
Szeged, Hungary
Seoul National University Hospital, Department of Internal Medicine
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center/Division of Nephrology
🇰🇷
Seoul, Korea, Republic of
Eulji General Hospital
🇰🇷
Seoul, Korea, Republic of
Vilnius University Hospital Santariskiu Clinic, Public Institution, Centre of Nephrology
🇱🇹
Vilnius, Lithuania
Zaklad Diagnostyki Chorob Serca, II Katedra Kardiologii
🇵🇱
Gdansk, Poland
Pracownia Echokardiografii, Oddzial Kardiologii
🇵🇱
Olsztyn, Poland
Klinika Kardiologii
🇵🇱
Szczecin, Poland
Univerzitna nemocnica Bratislava
🇸🇰
Limbova 5, Bratislava, Slovakia
Hospital Clinic I Provincial de Barcelona
🇪🇸
Barcelona, Spain
Sahlgrenska Universitetssjukhuset, Njurmedicin
🇸🇪
Goteborg, Sweden
Universitaetsspital Zuerich
🇨🇭
Zuerich, Switzerland
Karolinska Universitetssjukhuset Huddinge
🇸🇪
Stockholm, Sweden
Istanbul University, Istanbul Tip Fakultesi
🇹🇷
Istanbul, Capa, Turkey
BHF Glasgow Cardiovascular Research Centre, University of Glasgow
🇬🇧
Glasgow, United Kingdom
Renal and Urology Directorate, Leicester General Hospital
🇬🇧
Leicester, United Kingdom
Specjalistyczny Szpital Zachodni im. Jana Pawla II w Grodzisku Mazowieckim
🇵🇱
Grodzisk Mazowiecki, Poland
Krakowskie Centrum Medyczne NZOZ
🇵🇱
Krakow, Poland
SPITALUL CLINIC JUDETEAN DE URGENTA TIMISOARA ,Clinica de Nefrologie
🇷🇴
Timisoara, Romania
Fakultni poliklinika VFN
🇨🇿
Praha 2, Czech Republic
Pharmaceutical Research Associates CZ, s.r.o.
🇨🇿
Praha 7, Czech Republic
Spitalul Clinic Municipal Dr. Gavril Curteanu Oradea
🇷🇴
Oradea, jud. Bihor, Romania
SUMMIT CLINICAL RESEARCH, s.r.o., Oddelenie internej mediciny a klinickej farmakologie
🇸🇰
Bratislava, Slovakia
Klinika Nefrologii, Transplantologii i Chorob Wewnetrznych
🇵🇱
Szczecin, Poland
SPZOZ Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego
🇵🇱
Wroclaw, Poland
Klinika gerontologicka a metabolicka
🇨🇿
Hradec Kralove, Czech Republic
Spitalul Clinic Republican
🇲🇩
Chisinau, Moldova, Republic of
Hospital Universitari de Bellvitge
🇪🇸
Hospitalet de Llobregat, Barcelona, Spain
Southwest Clinical Research Institute, LLC
🇺🇸
Tempe, Arizona, United States
Spitalul Clinic Dr. C. I. Parhon Iasi
🇷🇴
Iasi, jud. Iasi, Romania
Morriston Hospital
🇬🇧
Swansea, Wales, United Kingdom
Istituti Ospitalieri di Cremona
🇮🇹
Cremona, Italy
A.O. Universitaria Ospedali Riuniti di Foggia
🇮🇹
Foggia, Italy
Dokuz Eylul Universitesi Hastanesi Ic Hastaliklari Anabilim Dali
🇹🇷
Izmir, Inciralti/ Narlidere, Turkey
Centrum Medyczne Aesculap
🇵🇱
Radom, Poland
Klinika Nefrologii, Hipertensjologii i Chorob Wewnetrznych Katedry Chorob Wewnetrznych UWM
🇵🇱
Olsztyn, Poland
Doylestown Hospital MRI
🇺🇸
Doylestown, Pennsylvania, United States
Renal Associates of Baton Rouge
🇺🇸
Baton Rouge, Louisiana, United States
Washington University
🇺🇸
St. Louis, Missouri, United States
Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Boise Kidney & Hypertension Institute, PLLC
🇺🇸
Meridian, Idaho, United States
Nemocnice Nove Mesto na Morave
🇨🇿
Nove Mesto na Morave, Czech Republic
PRA Magyarorszag Kft. Klinikai Farmakologiai Vizsgalohely
🇭🇺
Budapest, Hungary
Szpital Powiatowy w Wolominie
🇵🇱
Wolomin, Poland
Institutul Clinic Fundeni, Centrul de Medicina Interna-Nefrologie
🇷🇴
Bucuresti, Romania
Karolinska Universitetssjukhuset Solna
🇸🇪
Stockholm, Sweden
The Polyclinic
🇺🇸
Seattle, Washington, United States
Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
Fovarosi Onkormanyzat Szent Imre Korhaz BSZMI Klinikai Farmakologiai Reszlege
🇭🇺
Budapest, Hungary