Clinical trial NCT00401583: A Study To Test The Effect Of GW786034 (Pazopanib) On P450 Enzymes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Renal Cell
Keywords: GW786034 (pazopanib) cytochrome P450 interaction
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-11-20
Enrollment: 24
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: To investigate the potential of GW786034 to inhibit or induce various CYP450 enzymes.
timeFrame: throughout the study
Secondary outcomes:
measure: 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.
timeFrame: throughout the study
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: GSK Investigational Site
state: New Hampshire
city: Singapore
country: Singapore
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29.