Study to Assess the Pharmacokinetics of Cabozantinib (XL184) in Hepatic Impaired Adult Subjects

Study Overview
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Brief Summary
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The main objective of this study is to compare the pharmacokinetics (PK) of a single oral 75 mg dose of cabozantinib in hepatic impaired adult subjects to 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 I, Open-Label, Parallel-Group, Single-Dose Study to Assess the Pharmacokinetics of XL184 (Cabozantinib) Capsules in Hepatic Impaired Adult Subjects

Conditions
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Healthy, Hepatic 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 of ≥18 (kg/m2) and ≤36.0 (kg/m2). Must use acceptable forms 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 hepatic function: healthy normal adult subjects | Drug: cabozantinib<br>* 3 25-mg strength capsules (75-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 hepatic impairment: adult subjects with a Child-Pugh grade A (score 5-6). | Drug: cabozantinib<br>* 3 25-mg strength capsules (75-mg dose) administered as a single oral dose on Day 1 of study participation<br>* Other names: XL184;|
| Experimental: Group 3<br>Moderate hepatic impairment: adult subjects with a Child-Pugh grade B (score 7-9). | Drug: cabozantinib<br>* 3 25-mg strength capsules (75-mg dose) administered as a single oral dose on Day 1 of study participation<br>* Other names: XL184;|
| Experimental: Group 4<br>Severe hepatic impairment: adult subjects with a Child-Pugh grade C (score 10-15). | Drug: cabozantinib<br>* 3 25-mg strength capsules (75-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 |
| --- | --- | --- |
| AUC, Cmax, tmax, t1/2, CL/F, and V/F parameters as a measure of the PK of a single oral 75 mg dose of cabozantinib in hepatic impaired adult subjects compared to healthy adult subjects matched for age, gender, body mass index (BMI), and ethnicity | Subjects will receive a single oral 75 mg dose of cabozantinib on Day 1 and then undergo periodic assessments Days 1 through 5 following this single dose, as well as on the mornings of Days 6, 8, 11, 15, 19, 21, and 22. | Days 1 - 5, 6, 8, 11, 15, 19, 21, and 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events, serious adverse events, and laboratory abnormalities as a measure of the safety and tolerability of a single oral 75 mg dose in hepatic impaired adult subjects and healthy adult subjects |  | Days 1 - 5, 6, 8, 11, 15, 19, 21, and 22 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normal healthy adult subjects, Adult subjects with hepatic impairment