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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00659555
First received: April 10, 2008
Last updated: March 15, 2012
Last verified: February 2011
  Purpose

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


Condition Intervention Phase
Macular Degeneration
Age-related Macular Degeneration
Drug: pazopanib eye drops and ketoconazole tablets
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Two-period, Fixed-sequence Study in Healthy Volunteers to Evaluate the Effects of Repeat Oral Dosing of Ketoconazole on the Pharmacokinetics of a Single Dose of Pazopanib (GW786034) Administered as Eye Drops

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Pazopanib exposure measured by AUC anc Cmax.

Secondary Outcome Measures:
  • General safety measured by clinical laboratory tests, vital signs, cardiac monitoring and AE reporting. Pazopanib exposure as measured by additional pharmacokinetic parameters.
  • Additional pharmacokinetic endpoints will include pazopanib AUC(0-t), tmax ans t½.

Enrollment: 22
Study Start Date: April 2008
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: pazopanib eye drops and ketoconazole tablets
    Other Name: pazopanib eye drops and ketoconazole tablets
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Healthy as determined by a trained health care professional, base on a medical evaluation including medical history, physical examination, laboratory tests and 12-lead ECG. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects with ALT or AST values above the normal limit should be excluded from enrollment.
  • Male or female greater than 18 years of age.
  • A female subject is eligible to participate if she is of:

    • Non-childbearing potential defined as pre-menopausal females with a document tubal ligation/occlusion or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample showing simultaneous follicle stimulating hormone (FSH)> 40MIU/ml and estradiol < 40 pg/ml (<140 pmol/L) may be used to confirm that a woman is postmenopausal].
  • BMI within the range 18-30 kg/m2 (inclusive).
  • Capable of giving written informed consent and complying with the requirements and restrictions listed in the consent form.
  • QTcB or QTcF < 450 msec; or QTc <480 msec in subjects with Bundle Branch Block.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659555

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00659555     History of Changes
Other Study ID Numbers: MD7110861
Study First Received: April 10, 2008
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
vascular endothelial growth factor,
drug interaction,
angiogenesis,
pharmacokinetics,
age-related macular degeneration,
pazopanib,
ketoconazole

Additional relevant MeSH terms:
Macular Degeneration
Eye Diseases
Retinal Degeneration
Retinal Diseases
Ketoconazole
Ophthalmic Solutions
Tetrahydrozoline
14-alpha Demethylase Inhibitors
Anti-Infective Agents
Antifungal Agents
Autonomic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nasal Decongestants
Peripheral Nervous System Agents
Pharmaceutical Solutions
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sympathomimetics
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 23, 2014