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

• ClinicalTrials.gov Identifier: NCT01761773
• Recruitment Status: Completed
• First Posted: January 7, 2013
• Last Update Posted: September 22, 2014
• Sponsor: Exelixis
• Information provided by (Responsible Party): Exelixis

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy; Renal Impairment	Drug: cabozantinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Parallel-Cohort, Single-Dose Study to Assess the Pharmacokinetics of Cabozantinib (XL184) Capsules in Subjects With Impaired Renal Function
• Study Start Date: December 2012
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: July 2014

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: XL184

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics [ Time Frame: 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 :

1. Safety and Tolerability [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Miami, Florida, United States, 33136

Orlando, Florida, United States, 32809

United States, New Jersey

Neptune, New Jersey, United States, 07753

Sponsors and Collaborators

Exelixis

More Information

• Responsible Party: Exelixis
• ClinicalTrials.gov Identifier: NCT01761773
• Other Study ID Numbers: XL184-017
• First Posted: January 7, 2013
• Last Update Posted: September 22, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases