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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
172
Change From Baseline (CFB) in Total Kidney Volume (TKV) at Month 25
TKV was measured by centrally evaluated Magnetic Resonance Imaging (MRI).
Time frame: Baseline and Month 25 (end of Initial Treatment Period Visit [ITPV])
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Months 12, 24, 25 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 frame: Baseline, Month 12, Month 24, Month 25 (end of ITPV), and early termination
Time to First Occurrence or Worsening of Hypertension
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 frame: Baseline up to Month 25 (end of ITPV)
Time to First Occurrence or Worsening of Back and/or Flank Pain
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 frame: Baseline up to Month 25 (end of ITPV)
Time to First Occurrence of Gross Hematuria
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Southwest Kidney Institute, PLC
Phoenix, Arizona, United States
Southwest Clinical Research Institute, LLC
Tempe, Arizona, United States
Southwest Kidney Institute, PLC
Tempe, Arizona, United States
Capital Nephrology Clinical Research
Sacramento, California, United States
Boise Kidney & Hypertension Institute, PLLC
Caldwell, Idaho, United States
Boise Kidney & Hypertension Institute, PLLC
Meridian, Idaho, United States
Renal Associates of Baton Rouge
Baton Rouge, Louisiana, United States
Tufts Medical Center
Boston, Massachusetts, United States
Washington University School of Medicine
St Louis, Missouri, United States
Washington University
St Louis, Missouri, United States
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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 frame: Baseline up to Month 25 (end of ITPV)
Time to First Occurrence of Proteinuria
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 frame: Baseline up to Month 25 (end of ITPV)
Time to First Occurrence of End-Stage Renal Disease (ESRD) Requiring Dialysis >=56 Days
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.
Time frame: Baseline up to Month 25 (end of ITPV)
Number of Participants With High Blood Urea Nitrogen (BUN) Levels
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.
Time frame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Number of Participants With High Serum Creatinine (SCr) Levels
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.
Time frame: Day 15, Months 6, 12, 18, 24, and 25 (end of ITPV)
Maximum Observed Plasma Concentration (Cmax) of Bosutinib
Time frame: 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
Time frame: 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
Area under the concentration-time profile from time 0 to time tau, the dosing interval, where tau=24 hours.
Time frame: 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)
Lowest Concentration Observed During the Dosing Interval (Cmin) of Bosutinib
Time frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Apparent Oral Clearance (CL/F) of Bosutinib
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.
Time frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Apparent Volume of Distribution (Vz/F) of Bosutinib
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.
Time frame: 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)
Terminal Elimination Half-Life (t1/2) of Bosutinib
t1/2 is the time measured for the plasma concentration to decrease by one half.
Time frame: 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)
Observed Accumulation Ratio (Rac) of Bosutinib
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).
Time frame: Day 15 (pre-dose and 1, 2, 3, 4, 6, 8 and 24 hours post-dose)
Change From Baseline in Kidney Disease Quality of Life (KDQoL)-36 Scale Scores at 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.
Time frame: Baseline and end of ITPV (Month 25)