Clinical trial NCT00460707: A Study to Assess the Safety and Interaction Between Casopitant and Ketoconazole When Taken By Healthy Adults
Official title: A Phase I, Randomized, Double-Blind Study to Assess the Effects of Repeat Oral Dosing of Ketoconazole on the Pharmacokinetics of Repeat Oral Dosing of Casopitant in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nausea and Vomiting, Chemotherapy-Induced
Keywords: GW679769
healthy adult subjects
casopitant
ketoconazole
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-04-16
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Casopitant may affect liver enzymes that metabolize ketoconazole. This study is designed to test the safety and the extent of the Casopitant affect on ketoconazole levels in healthy human subjects.


Eligibility criteria: Inclusion criteria:

* A female subject who is non-childbearing potential or using acceptable contraceptive methods.
* Adequate organ system functions.
* Able to swallow and retain oral medication.
* Subject is able to understand and comply with protocol requirements and instruction and is likely to complete the study.

Exclusion Criteria:

* Current clinically relevant abnormality, medical condition, or circumstance that makes the subject unsuitable for the study per the study doctor.
* History of drug or other allergy which, in the opinion of the study doctor, contraindicates participation.
* Use of an investigational drug within 28 days or 5 half-lives.
* Use of prescription or non-prescription drugs, supplements or vitamins (excluding multivitamins) within 14 days, or 5 half-lives prior to first dose of study medication.
* Blood donation in excess of 500mL within 56 days prior to dosing or intends to donate within 30 days of the post-treatment follow-up visit.
* Iron deficiency.
* Positive stool for occult blood.
* Female subject who is pregnant or lactating.
* Male subject who has a history of hypogonadism.
* Positive urine drug screen.
* Positive for HIV antibody, hepatitis C antibody or hepatitis B surface antigen.
* Use of tobacco-containing products within the past 12 months prior to screening.
* History of drug or alcohol abuse or dependence within 6 months of screening.
* History or presence of uncontrolled emesis.
* Presence of active infection.
* History of cholecystectomy or biliary tract disease.
* Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology.
* Any degree of heart failure.
* Consumption of any food or drink containing grapefruit or grapefruit juice, apple juice, Seville oranges, kumquats, pommelos or vegetables from the mustard green family within 7 days prior to the first dose unless prior approval is received.

Primary outcomes:
measure: Plasma levels of casopitant and ketoconazole will be checked on Day 4 to 9 in Cohort 1.
timeFrame: Day 4 to 9 in Cohort 1.
measure: Plasma levels of casopitant will be checked on Day 2 to 4 of Period 1 and
timeFrame: Day 2 to 4 of Period 1
measure: casopitant and ketoconazole will be checked on Day 4 to 9 of Period 2.
timeFrame: Day 4 to 9 of Period 2
Secondary outcomes:
measure: Safety is evaluated in Cohort 1 by: - Clinical Lab Tests & Physical Exam at Screen, Day -1 & Followup (FU)
timeFrame: at Screen, Day -1 & Followup (FU)
measure: - Vitals Signs monitored at Screen, Day -1, 4-7 and FU
timeFrame: at Screen, Day -1, 4-7 and FU
measure: - 12 lead ECGs at Screen & FU
timeFrame: at Screen & FU
measure: - Adverse Events Monitoring starting at Day 1
timeFrame: Day 1
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: GSK Investigational Site
state: Kansas
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Johnson BM, Adams LM, Zhang K, Gainer SD, Kirby LC, Blum RA, Apseloff G, Morrison RA, Schutz RA, Lebowitz PF. Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist. J Clin Pharmacol. 2010 Aug;50(8):951-9. doi: 10.1177/0091270009353761. Epub 2010 Feb 2.