Clinical trial NCT00404378: Study Of Healthy Subjects To Assess The Effect Of Ketoconazole And The Way The Body Will React To Casopitant [GW679769]
Official title: An Open-label, Two Period, Fixed Sequence Study of Healthy Subjects to Assess the Effect of Repeat Oral Dosing of Ketoconazole on the Pharmacokinetics of a Single Oral Dose of [GW679769]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Nausea and Vomiting, Chemotherapy-Induced
Keywords: Healthy subjects
Pharmacokinetics
Drug interaction
Ketoconazole
Casopitant
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-11-28
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a two period study of healthy adult subjects to characterize the effect of the dosing of ketoconazole on the the way the body reacts to a dose of GW679769, and to assess the safety profile of oral casopitant with and without ketoconazole. This study will consist of a screening period, two treatment periods and a post-treatment follow-up visit.


Eligibility criteria: Inclusion Criteria:

* Healthy male or females
* Females must be of non-childbearing potential
* Adequate organ functions
* Able to swallow and retain oral medications
* Able to understand and comply with study requirements
* Signed ICF

Exclusion Criteria:

* Clinically relevant abnormality identified on the screening exam or any other medical condition or circumstance making the subject unsuitable for participation in the study.
* History of drug or other allergy which contraindicates participation.
* Known immediate hypersensitivity reaction or idiosyncrasy to GW679769 or ketoconazole or drugs chemically related to the study medications.
* Use of an investigational drug within 28 days preceding the first dose of GW679769 or ketoconazole or participation in another clinical trial within the past 30 days.
* Blood donation in excess of 1 pint within 56 days prior to first dose of study medication or intends to donate within 30 days of the post-treatment follow-up visit.
* History of or suspected iron deficiency.
* Positive stool for occult blood.
* Pepsinogen level below the lower limit of laboratory reference range (LLRR).
* Troponin level above 10% of the coefficient of variation of the assay as determined by the laboratory performing the test.
* For male subjects, any history of hypogonadism and treatments associated with hypogonadism including radiation therapy to the testicles.
* For female subjects, a positive serum ß-hCG (beta-human chorionic gonadotropin) pregnancy test.
* Female subject who is lactating.
* Positive urine drug screen (UDS) including alcohol.
* Positive for HIV antibody, hepatitis C antibody or hepatitis B surface antigen
* Positive urinary cotinine. Subjects must not have used any nicotine-containing products, including nicotine patches or gum, within the past 6 months.
* Smoking history = 4 packs per day/year or smoked within the past 12 months.
* History of drug abuse or dependence within the past 6 months.
* History of alcohol abuse within the past 6 months or alcohol consumption in the past 6 months exceeding study requirements
* Presence of uncontrolled nausea \& vomiting.
* Presence of an active infection.
* Any degree of heart failure as defined by the New York Heart Association functional classification system.
* Active peptic ulcer disease (PUD) or a history of PUD of unknown etiology.
* Use of any prescription or non-prescription drug(s), herbal or dietary supplements or vitamins within 14 days prior to the first dose of study medication.
* Consumption of any food or drink containing grapefruit or grapefruit juice, apple juice, Seville oranges, kumquats, pomelos or vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi and brussels sprouts, mustard) within 14 days prior to the first dose of study medication.
* History of cholecystectomy or biliary tract disease.
* Any serious or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study.

Primary outcomes:
measure: Plasma levels will be measured for casopitant at Period 1: Day 1, 2 & 3.
timeFrame: Period 1: Day 1, 2 & 3
measure: Plasma levels will be measured for casopitant and ketoconazole at Period 2: Day 4, 5, 6, 7, & 8.
timeFrame: Period 2: Day 4, 5, 6, 7, & 8.
Secondary outcomes:
measure: clinical lab tests monitoring of International Normalized Ratio (INR) adverse events vital signs 12 lead ECGs liver function tests
timeFrame: throughout the study
Other outcomes:
Locations:
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: