Conditions: Cancer
Keywords: Esomeprazole Pharmacogenetics Pharmacokinetics Ketoconazole Pazopanib Drug Interaction Safety Solid Tumors
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 34
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine how dosing with ketoconazole (Nizoral) or esomeprazole (Nexium) affects the pharmacokinetics of oral pazopanib. The study will also test for safety of pazopanib when administered with ketoconazole or esomeprazole.

Detailed description:
The study is a 2-arm, open-label, repeat-dose, single sequence, crossover, study designed to evaluate the effects of ketoconazole (Arm A) and esomeprazole (Arm B) on the pharmacokinetics (PK) of oral pazopanib in subjects with solid tumor malignancies. This study will compare the PK parameters of oral pazopanib and its metabolite concentrations when given alone and when co-administered with either ketoconazole (Arm A) or esomeprazole (Arm B). Safety assessments (physical examinations, vital signs, 12-lead electrocardiograms, Eastern Cooperative Oncology Group performance status, clinical laboratory assessments, and monitoring of adverse events) will also be evaluated during the study.

Arms:
arm 1: Administration of oral pazopanib 400mg (2 200-mg tablets) once-daily each morning for at least 7 consecutive doses during Period 1. Then administration of oral ketoconazole 400 mg (2 - 200 mg tablets) followed immediately by pazopanib 400 mg (2 -200 mg tablets) once-daily each morning for a total of 5 consecutive doses during Period 2. arm 2: Subjects will receive orally administered pazopanib 800mg (4 - 200mg tablets) once-daily each morning for at least 7 consecutive doses in Period 1. In the evening on the last day of Period 1, subjects will take their initial dose of esomeprazole 40 mg (1 - 40 mg capsule) approximately 3 hours after the evening meal. Subjects will continue to receive pazopanib (each morning) and esomeprazole each evening once-daily for a total of 5 consecutive doses.

Interventions: intervention 1: pazopanib
Intervention descriptions: intervention 1: Adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet derivative growth factor receptor (PDGFR)

Protocol document: