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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy, Renal Impairment

Intervention / Treatment
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* Drug: cabozantinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Group 1<br>Subjects with normal renal function: healthy normal adult subjects with an eGFR ≥ 90 mL/min/1.73m2. | Drug: cabozantinib<br>* 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.<br>* Other names: XL184;|
| Experimental: Group 2<br>Subjects with mild renal impairment: adult subjects with a eCFR ≥ 90 mL/min/1.73m2. | Drug: cabozantinib<br>* 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.<br>* Other names: XL184;|
| Experimental: Group 3<br>Moderate renal impairment: adult subjects with an eGFR between ≥30 - ≤ 59 mL/min/1.73m2. | Drug: cabozantinib<br>* 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.<br>* Other names: XL184;|
| Experimental: Group 4<br>Severe renal impairment: adult subjects with an eGFR ≤ 29 mL/min/1.73m2, not on dialysis. | Drug: cabozantinib<br>* 3 20-mg strength capsules (60 mg dose) administered as a single oral dose on Day 1 of study participation.<br>* Other names: XL184;|

What is the study measuring?
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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. |