Study Of The Repeat Dosing Of Ketoconazole On The Pharmacokinetics Of A Single Dose Of Pazopanib (GW786034) Eye Drops

Phase 1

Completed

• Conditions: Macular Degeneration
• Interventions: Drug: pazopanib eye drops; Drug: Ketoconozole tablets

• Registration Number: NCT00659555
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This is a two-period study to evaluate the effect of repeat oral dosing of ketoconazole on the pharmacokinetics of single dose pazopanib administered as an eye drop

Detailed Description

Not available

Study Timeline

• Study Start: 2008-04-04
• Study First Submitted: 2008-04-10
• Study First Submitted QC: 2008-04-10
• Study First Posted: 2008-04-16
• Primary Completion: 2008-05-10
• Study Completion: 2008-05-10
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-08
• Last Update Posted: 2017-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

• Current alcohol or illicit drug use which, in the judgment of the Investigator, would interfere with the subject's ability to comply with the dosing schedule or protocol-specified evaluations. For example, a history of regular alcohol consumption (defined below) within 6 months of screening would exclude a subject.

  • Regular alcohol consumption: an average weekly intake of >14 drinks/week for men or > 7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.

• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.

• HIV requiring treatment during the study period.

• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

• Use of prescription, non-prescription, or illicit drugs, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and the GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. (Note: this restriction includes ocular prescription and non-prescription drugs.)

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

• Any contraindication to use of ketoconazole as detailed in the package insert.

• Where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 56 day period.

• Pregnant females as determined by positive urine hCG test at screening or prior to dosing.

• Women planning to breastfeed an infant during the study period.

• Presence of ongoing ocular disease at the time of screening.

• Any eye surgery within three months prior to first dose of study medication.

• An unwillingness to refrain from wearing contact lenses during the study until completion of the follow-up visit.

• Urinary continine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.

• Consumption of red wine, Seville oranges (found in orange marmalade), grapefruit or grapefruit juice from 7 days prior to the first dose of study medication.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment B receivers	Ketoconozole tablets	Subjects received ketoconazole, daily 400 mg oral dose on Days 1 to 8; pazopanib, single dose as 2 x 40 microliter drops of 5 mg/mL solution on Day 5 in Period 2
Treatment A receivers	pazopanib eye drops	Subjects received pazopanib, single dose as 2 x 40 microliter drops of 5 mg/mL solution in Period 1
Treatment B receivers	pazopanib eye drops	Subjects received ketoconazole, daily 400 mg oral dose on Days 1 to 8; pazopanib, single dose as 2 x 40 microliter drops of 5 mg/mL solution on Day 5 in Period 2

Primary Outcome Measures

Name	Time	Method
Pazopanib exposure measured by AUC anc Cmax.	Up to 2 months

Secondary Outcome Measures

Name	Time	Method
General safety measured by clinical laboratory tests, vital signs, cardiac monitoring and AE reporting. Pazopanib exposure as measured by additional pharmacokinetic parameters.	Up to 2 months
Additional pharmacokinetic endpoints will include pazopanib AUC(0-t), tmax ans t½.	Up to 2 months

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Buffalo, New York, United States