A Study To Test The Effect Of GW786034 (Pazopanib) On P450 Enzymes

Study Overview
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Brief Summary
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This is a Phase I study to determine the effect of GW786034 (pazopanib) on P450 enzymes. This study will help determine which types of drugs may interact with GW786034.

Official Title
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A Multi-center, Open-Label, Multiple-probe Drug Interaction Study to Determine the Effects of GW786034 on the Metabolism of Cytochrome P450 Probe Drugs in Patients With Solid Tumors

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: GW786034 (pazopanib)
* Drug: Probe drugs


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically or cytologically confirmed diagnosis of advanced solid tumors. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate bone marrow, renal, lung, and liver function. A female subject must not be pregnant and will agree not to become pregnant during the trial Exclusion criteria: Any major surgery, chemotherapy, hormone therapy, investigational drugs, or radiotherapy within the last 28 days. Poorly controlled hypertension. Corrected QT (QTc) prolongation defined as a QTc interval greater than or equal to 480 msec and a prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities. Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months. Current use of therapeutic anticoagulation (low molecular weight heparin, oral anticoagulant agents). Amiodarone must not have been taken for at least 6 months prior to the administration of the first dose of study drug. History of brain metastases. Has narrow-angle glaucoma which is a contraindication to midazolam use. History of nicotine-containing product (including cigarettes, cigars, nicotine patches) use within the past 6 months. A history of bleeding problems.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib receivers<br>During Days 1 and 2 subjects will be dosed with only probe drugs, and with no drugs on Days 3-5. During Days 6 to the end of the study, subjects will receive 800 mg daily pazopanib, and on Days 23-24 subjects will receive probe drugs in addition to pazopanib | Drug: GW786034 (pazopanib)<br>* Pazopanib will be given as monohydrochloride, 100 and 500 mg tablets.<br>Drug: Probe drugs<br>* probe drugs will be oral midazolam (3 mg), warfarin (10 mg), omeprazole (40 mg), caffeine (200 mg), and dextromethorphan (30 mg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the potential of GW786034 to inhibit or induce various CYP450 enzymes. |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of co-administration of 800 mg daily GW786034 and CYP450 probe drugs. To describe GW786034 steady-state pharmacokinetics on this once daily dosing regimen. |  | throughout the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW786034 (pazopanib) cytochrome P450 interaction