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

A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Assess the Pharmacokinetics of Cabozantinib (XL184) Capsules in Subjects With Impaired Renal Function

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Renal Impairment
• Intervention / Treatment: Drug: cabozantinib

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
    • Orlando, Florida, United States, 32809
  • New Jersey
    • Neptune, New Jersey, United States, 07753

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 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: Group 1; Subjects with normal renal function: healthy normal adult subjects with an eGFR ≥ 90 mL/min/1.73m2.	Drug: cabozantinib; 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.; Other Names: XL184
Experimental: Group 2; Subjects with mild renal impairment: adult subjects with a eCFR ≥ 90 mL/min/1.73m2.	Drug: cabozantinib; 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.; Other Names: XL184
Experimental: Group 3; Moderate renal impairment: adult subjects with an eGFR between ≥30 - ≤ 59 mL/min/1.73m2.	Drug: cabozantinib; 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.; Other Names: XL184
Experimental: Group 4; Severe renal impairment: adult subjects with an eGFR ≤ 29 mL/min/1.73m2, not on dialysis.	Drug: cabozantinib; 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.; Other Names: XL184

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	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.	Days 1 - 8 as well as the morning of Days 11, 13, 15, 18, 21, 22.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	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.	Days 1 - 8 and Days 11, 13, 15, 18, 21, 22.

Collaborators and Investigators

• Sponsor: Exelixis

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: January 3, 2013
• First Submitted That Met QC Criteria: January 4, 2013
• First Posted (Estimate): January 7, 2013

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 19, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: XL184-017