A multicenter, randomized, double-blind, placebo-controlled study of the safety, effectiveness, and pharmacokinetics of bosutinib versus placebo in subjects with polycystic kidney disease
- Conditions
- Autosomal Dominant Polycystic Kidney Disease (ADPKD)MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2010-023017-65-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 169
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Males and females, aged =18 years to 50 years at the time of consent.
3. Documented diagnosis of ADPKD (PKD-1 or PKD-2 genotypes permitted) by renal
ultrasound based on the Unified Criteria for Ultrasonographic Diagnosis of ADPKD.
4. Total kidney volume =750 cc, as measured by centrally evaluated MRI.
5. Left ventricular ejection fraction by echocardiogram or MUGA =50% at screening.
6. All women of childbearing potential must have a negative pregnancy test result before administration of study drug. Because the effect of bosutinib on the efficacy of orally or transdermally administered contraceptives is unknown, women of childbearing potential must agree to use 2 medically acceptable nonhormonal methods of contraception (eg, condom with a spermacide) for at least 14 days prior to the first dose of study medication and continue until 28 days after dosing. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or those women whose sexual partners are either considered sterile or are using contraceptives. Any pregnancy that occurs in any female subject in the trial must be reported if it occurs at any time during the active treatment phase of the study and for 4 weeks after the last dose of study drug. Any female who becomes pregnant during the active treatment phase must discontinue further therapy.
7. Men willing to use 2 medically acceptable methods of contraceptions (eg, condom with a spermacide) throughout the active treatment phase of the study and for 4 weeks after the last dose of study drug. Any pregnancy that occurs in the female partner of a male subject in the trial must be reported if it occurs at any time during the active treatment phase of the study or for 4 weeks after the last dose of study drug.
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 275
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects presenting with any of the following will not be included in the study:
1. Weight <40 kg or >100 kg.
2. Women who are pregnant or breastfeeding or women who intend to become pregnant in the next two years.
3. Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 for primary treatment population. Subjects with moderate renal impairment (defined as 30 mL/min/1.73m2 = eGFR =50mL/min/1.73m2) are excluded (from enrollment in an exploratory population) until results from a separate renal impairment PK study (study B1871020) demonstrate no substantial impact of renal impairment on bosutinib PK. Subjects with an eGFR<30 mL/min/1.73m2 will be excluded.
4. Abnormal urinalysis showing casts.
5. Biopsy proven renal disease other than ADPKD.
6. Chronic back and/or flank pain requiring daily or near daily pain medication over the preceding month.
7. Documented renal vascular disease.
8. Documented systemic illness with renal involvement.
9. Creatinine supplements within 3 months of the baseline visit.
10. Uncontrolled hypertension (defined as systolic blood pressure =140 or diastolic blood pressure =90 mm Hg).
11. Increased ALT and/or AST >2.5 x the upper limit of normal.
12. Total bilirubin >2 x the upper limit of normal (unless associated with Gilbert’s syndrome).
13. Grade 2 or higher abnormalities of serum sodium [sodium >150 or <130 mmol/l].
14. Uncorrected hypomagnesemia or hypokalemia [serum magnesium or serum potassium < lower limit of normal].
15. Grade 2 or higher elevation of serum potassium or serum magnesium [serum potassium >5.5 or serum magnesium >3.0 mg/dl (or >1.23 mmol/l)].
16. Hemoglobin <9.0 gm/dl.
17. Congenital absence of a kidney or prior surgical resection of a kidney for any reason.
18. Clinically significant or unstable cardiac disease (eg, unstable angina, recent myocardial infarction, clinically significant arrhythmia requiring treatment, uncontrolled congestive heart failure, etc).
19. Subjects with any pre-dose corrected QT interval (QTc) =450 msec based on any one of the machine-read tracing using Fridericia’s formulae obtained at screening. Any decision to retest a subject must first be discussed with the Pfizer Medical Monitor. If a repeat QTc interval obtained pre-dose is =450 msec, the subject is excluded from enrollment.
20. History of prolonged QTc interval or additional risk factors for Torsade de Pointes (eg, heart failure, hypokalemia, family history of long QT syndrome).
21. Infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
22. Past or present malignancy (with the exception of adequately treated, localized basal cell or squamous cell carcinoma of the skin).
23. Use of any investigational drug or investigational biologic compound within weeks
prior to the screening visit or during the screening period.
24. Participation in any interventional studies within 4 weeks prior to the screening visit and/or during study participation.
25. Any previous exposure to the bosutinib study drug, including p
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method