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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01233869




Registration number
NCT01233869
Ethics application status
Date submitted
28/10/2010
Date registered
3/11/2010
Date last updated
11/03/2016

Titles & IDs
Public title
Bosutinib For Autosomal Dominant Polycystic Kidney Disease
Scientific 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)
Secondary ID [1] 0 0
3160A7-2211
Secondary ID [2] 0 0
B1871019
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycystic Kidney, Autosomal Dominant 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bosutinib
Treatment: Drugs - Bosutinib
Treatment: Drugs - Placebo

Experimental: Cohort A -

Experimental: Cohort B -

Placebo comparator: Cohort C -


Treatment: Drugs: Bosutinib
Once daily oral dose of 200 mg of bosutinib

Treatment: Drugs: Bosutinib
Once daily oral dose of 400 mg of bosutinib transitioned to 200 mg/day

Treatment: Drugs: Placebo
Once daily oral dose of placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25
Timepoint [1] 0 0
Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])
Secondary outcome [1] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 and Early Termination
Timepoint [1] 0 0
Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination
Secondary outcome [2] 0 0
Time to First Occurrence or Worsening of Hypertension
Timepoint [2] 0 0
Baseline up to Month 25 (end of ITPV)
Secondary outcome [3] 0 0
Time to First Occurrence or Worsening of Back and/or Flank Pain
Timepoint [3] 0 0
Baseline up to Month 25 (end of ITPV)
Secondary outcome [4] 0 0
Time to First Occurrence of Gross Hematuria
Timepoint [4] 0 0
Baseline up to Month 25 (end of ITPV)
Secondary outcome [5] 0 0
Time to First Occurrence of Proteinuria
Timepoint [5] 0 0
Baseline up to Month 25 (end of ITPV)
Secondary outcome [6] 0 0
Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days
Timepoint [6] 0 0
Baseline up to Month 25 (end of ITPV)
Secondary outcome [7] 0 0
Number of Participants With High Blood Urea Nitrogen (BUN) Levels
Timepoint [7] 0 0
Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Secondary outcome [8] 0 0
Number of Participants With High Serum Creatinine (SCr) Levels
Timepoint [8] 0 0
Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Secondary outcome [9] 0 0
Maximum Observed Plasma Concentration (Cmax) of Bosutinib
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bosutinib
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Area Under the Concentration-Time Profile From Time 0 to the Dosing Interval (AUCtau) of Bosutinib
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib
Timepoint [12] 0 0
Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Secondary outcome [13] 0 0
Apparent Oral Clearance (CL/F) of Bosutinib
Timepoint [13] 0 0
Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Secondary outcome [14] 0 0
Apparent Volume of Distribution (Vz/F) of Bosutinib
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Terminal Elimination Half-Life (t1/2) of Bosutinib
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Observed Accumulation Ratio (Rac) of Bosutinib
Timepoint [16] 0 0
Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Secondary outcome [17] 0 0
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at Month 25
Timepoint [17] 0 0
Baseline and end of ITPV (Month 25)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2014
Sample size
Target
Accrual to date
Final
172
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Idaho
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Czech Republic
State/province [14] 0 0
Hradec Kralove
Country [15] 0 0
Czech Republic
State/province [15] 0 0
Liberec 1
Country [16] 0 0
Czech Republic
State/province [16] 0 0
Nove Mesto na Morave
Country [17] 0 0
Czech Republic
State/province [17] 0 0
Praha 2
Country [18] 0 0
Czech Republic
State/province [18] 0 0
Praha 7
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Hungary
State/province [20] 0 0
Szeged
Country [21] 0 0
Italy
State/province [21] 0 0
Cremona
Country [22] 0 0
Italy
State/province [22] 0 0
Foggia
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Lithuania
State/province [24] 0 0
Vilnius
Country [25] 0 0
Moldova, Republic of
State/province [25] 0 0
Chisinau
Country [26] 0 0
Poland
State/province [26] 0 0
Gdansk
Country [27] 0 0
Poland
State/province [27] 0 0
Grodzisk Mazowiecki
Country [28] 0 0
Poland
State/province [28] 0 0
Krakow
Country [29] 0 0
Poland
State/province [29] 0 0
Olsztyn
Country [30] 0 0
Poland
State/province [30] 0 0
Radom
Country [31] 0 0
Poland
State/province [31] 0 0
Szczecin
Country [32] 0 0
Poland
State/province [32] 0 0
Wolomin
Country [33] 0 0
Poland
State/province [33] 0 0
Wroclaw
Country [34] 0 0
Romania
State/province [34] 0 0
jud. Bihor
Country [35] 0 0
Romania
State/province [35] 0 0
jud. Iasi
Country [36] 0 0
Romania
State/province [36] 0 0
Bucuresti
Country [37] 0 0
Romania
State/province [37] 0 0
Timisoara
Country [38] 0 0
Slovakia
State/province [38] 0 0
Bratislava
Country [39] 0 0
Spain
State/province [39] 0 0
Barcelona
Country [40] 0 0
Sweden
State/province [40] 0 0
Goteborg
Country [41] 0 0
Sweden
State/province [41] 0 0
Stockholm
Country [42] 0 0
Switzerland
State/province [42] 0 0
Zuerich
Country [43] 0 0
Turkey
State/province [43] 0 0
Capa
Country [44] 0 0
Turkey
State/province [44] 0 0
Inciralti/ Narlidere
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Wales
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Glasgow
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Leicester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01233869
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01233869