A Single-Dose Study to Assess the Pharmacokinetics of Cabozantinib (XL184) Capsules in Subjects With Impaired Renal Function

Phase 1

Completed

• Conditions: Healthy; Renal Impairment
• Interventions: Drug: cabozantinib

• Registration Number: NCT01761773
• Lead Sponsor: Exelixis

Brief Summary

The main objective of the trial is to compare the pharmacokinetics of a 60 mg dose of cabozantinib in adult subjects with impaired renal function compared with healthy adult subjects. Another objective is to assess the safety and tolerability of cabozantinib in these adult subjects.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-01-03
• Study First Submitted QC: 2013-01-04
• Study First Posted: 2013-01-07
• Primary Completion: 2013-04
• Study Completion: 2014-07
• Status Verified: 2014-09
• Last Update Submitted: 2014-09-19
• Last Update Posted: 2014-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Body weight must be ≥ 50 kg and < 130 kg with a BMI ≤ 38.0 (kg/m2).
• Must use acceptable form of birth control during the course of the study and for 3 months following the single dose of study drug.
• Female subjects of childbearing potential must have a negative pregnancy test at screening and check-in.
• Negative test for HIV; hepatitis A, B, and C.
• Must have adequate vital sign reads at screening and check-in.
• Must be able to comply with dietary and fluid restrictions required for the study.

Exclusion Criteria

• History of medical or surgical conditions that would interfere with GI absorption, distribution, metabolism, or excretion of the study drug.
• Recent clinical evidence of pancreatic injury.
• Recent use of drugs known to significantly inhibit or induce P450 CYP3A4 enzymes.
• Previous diagnosis of malignancy.
• Unwilling to forgo use of any over-the-counter or non-prescription preparations.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 3	cabozantinib	Moderate renal impairment: adult subjects with an eGFR between ≥30 - ≤ 59 mL/min/1.73m2.
Group 2	cabozantinib	Subjects with mild renal impairment: adult subjects with a eCFR ≥ 90 mL/min/1.73m2.
Group 4	cabozantinib	Severe renal impairment: adult subjects with an eGFR ≤ 29 mL/min/1.73m2, not on dialysis.
Group 1	cabozantinib	Subjects with normal renal function: healthy normal adult subjects with an eGFR ≥ 90 mL/min/1.73m2.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics	Days 1 - 8 as well as the morning of Days 11, 13, 15, 18, 21, 22.	AUC, Cmax, tmax, kel, t1/2, CL/F, V/F and fu as measure of a single oral 60 mg dose of cabozantinib in adults with impaired renal function compared with healthy subjects matched for age, gender, and body mass index (BMI).; Subjects will receive a single oral 60 mg dose of cabozantinib on Day 1 and then undergo periodic assessments Days 1 - 8 following this single dose, as well as on the mornings of Days 11, 13, 15, 18, 21, 22.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability	Days 1 - 8 and Days 11, 13, 15, 18, 21, 22.	Number of participants with adverse events, serious adverse events, and laboratory abnormalities as a measure of the safety and tolerability of a single oral 60 mg dose in adult subjects with impaired renal function and in healthy adult subjects.