Bosutinib In Subjects With Renal Impairment

Study Overview
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Brief Summary
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This is a two-staged study of a single dose of 200 mg of bosutinib given to subjects with renal impairment and matching healthy volunteers. In Stage 1, only subjects with severe renal impairment and subjects with normal renal function will be enrolled. Subjects with mild and moderate renal impairment will be enrolled in Stage 2 if the results from Stage 1 suggest a substantial difference in PK profiles between subjects with severe renal impairment and subjects with normal renal function.

Official Title
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An Open-Label, Single-Dose, Parallel-Group Study Of The Pharmacokinetics And Safety Of Bosutinib In Subjects With Renal Impairment And Matched Healthy Adults

Conditions
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Renal Disease, End-Stage, Renal Insufficiency, Chronic, Renal Insufficiency, Acute

Intervention / Treatment
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* Drug: Bosutinib
* Drug: Bosutinib
* Drug: Bosutinib
* Drug: Bosutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, aged 18 to 65. Adequate hepatic function. Documented creatinine clearance by Cockroft-Gault formula indicative of the respective level of renal impairment: Severe renal impairment (CrCl <30 mL/min/1.73m2), moderate renal impairment (30 ≤ CrCl ≤50 mL/min/1.73m2), mild renal impairment (50 < CrCl≤80 mL/min/1.73m2) and normal renal function (CrCl >80 mL/min/1.73m2). Exclusion Criteria: Use of any investigational drug or biologic within 4 weeks prior to the screening visit of during the screening period. Ongoing treatment with Digoxin or strong CYP3A4 inhibitors or inducers. Uncontrolled hypertension (for renally impaired subjects only).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers<br> | Drug: Bosutinib<br>* Single dose of 200 mg of bosutinib in subjects with normal renal function<br>|
| Experimental: Mild Renal Impairment<br> | Drug: Bosutinib<br>* Single dose of 200 mg of bosutinib in subjects with mild renal impairment<br>|
| Experimental: Moderate Renal Impairment<br> | Drug: Bosutinib<br>* Single dose of 200 mg of bosutinib in subjects with moderate renal impairment<br>|
| Experimental: Severe Renal Impairment<br> | Drug: Bosutinib<br>* Single dose of 200 mg of bosutinib in subjects with severe renal impairment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentrations of bosutinib and its active metabolites will be measured, PK parameters (AUCinf, Cmax, AUClast, Tmax, t1/2, Cl/F and Vz/F) of bosutinib and its active metabolites will be calculated. |  | 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoints to include adverse events, physical examination findings, changes in clinical laboratory test results including ECGs, and changes in vital signs |  | 11 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal impairment, healthy volunteers