Bosutinib In Subjects With Renal Impairment

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Renal Insufficiency, Acute; Renal Disease, End-Stage
• Intervention / Treatment: Drug: Bosutinib; Drug: Bosutinib; Drug: Bosutinib; Drug: Bosutinib

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
    • Gainesville, Florida, United States, 32608
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33169
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32806
      • Pfizer Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: November 2, 2010
• First Posted (Estimate): November 3, 2010

Study Record Updates

• Last Update Posted (Estimate): July 3, 2012
• Last Update Submitted That Met QC Criteria: June 29, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: healthy volunteers; Renal impairment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: B1871020