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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 85
- Locations
- 1
- Primary Endpoint
- Plasma levels of casopitant and ketoconazole will be checked on Day 4 to 9 in Cohort 1.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
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.
Arms & Interventions
Cohort 1
All subjects in Cohort 1 will receive ketoconazole 400 milligrams (mg) once daily on Day 1 to 9 and oral casopitant 150 mg on Day 4 and 50 mg on Day 5 and Day 6 of treatment period 1. After a washout period of 21 days, subjects will be administered oral casopitant 150 mg on Day 1 and 50 mg on Day 2 and Day 3 of treatment period 2.
Intervention: Casopitant 150 mg (Drug)
Cohort 1
All subjects in Cohort 1 will receive ketoconazole 400 milligrams (mg) once daily on Day 1 to 9 and oral casopitant 150 mg on Day 4 and 50 mg on Day 5 and Day 6 of treatment period 1. After a washout period of 21 days, subjects will be administered oral casopitant 150 mg on Day 1 and 50 mg on Day 2 and Day 3 of treatment period 2.
Intervention: Ketoconazole (Drug)
Cohort 1
All subjects in Cohort 1 will receive ketoconazole 400 milligrams (mg) once daily on Day 1 to 9 and oral casopitant 150 mg on Day 4 and 50 mg on Day 5 and Day 6 of treatment period 1. After a washout period of 21 days, subjects will be administered oral casopitant 150 mg on Day 1 and 50 mg on Day 2 and Day 3 of treatment period 2.
Intervention: Casopitant 50 mg (Drug)
Cohort 2, Group A
Subjects will receive placebo once daily on Day 1 to Day 3 in treatment period 1. Subjects will receive ketoconazole 400 mg once daily on Day 1 to Day 9 and oral placebo once daily on Days 4, 5 and 6 in treatment period 2. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Ketoconazole (Drug)
Cohort 2, Group A
Subjects will receive placebo once daily on Day 1 to Day 3 in treatment period 1. Subjects will receive ketoconazole 400 mg once daily on Day 1 to Day 9 and oral placebo once daily on Days 4, 5 and 6 in treatment period 2. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Casopitant 150 mg matching placebo (Drug)
Cohort 2, Group A
Subjects will receive placebo once daily on Day 1 to Day 3 in treatment period 1. Subjects will receive ketoconazole 400 mg once daily on Day 1 to Day 9 and oral placebo once daily on Days 4, 5 and 6 in treatment period 2. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Casopitant 50 mg matching placebo (Drug)
Cohort 2, Group B
In treatment period 1, subjects will receive oral casopitant 150 mg on Day 1 and 50 mg on Days 2 and 3. In treatment period 2, they will be administered ketoconazole 400 mg once daily on Day 1 to Day 9 and oral casopitant 150 mg on Day 4 and 50 mg on Days 5 and 6. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Casopitant 150 mg (Drug)
Cohort 2, Group B
In treatment period 1, subjects will receive oral casopitant 150 mg on Day 1 and 50 mg on Days 2 and 3. In treatment period 2, they will be administered ketoconazole 400 mg once daily on Day 1 to Day 9 and oral casopitant 150 mg on Day 4 and 50 mg on Days 5 and 6. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Ketoconazole (Drug)
Cohort 2, Group B
In treatment period 1, subjects will receive oral casopitant 150 mg on Day 1 and 50 mg on Days 2 and 3. In treatment period 2, they will be administered ketoconazole 400 mg once daily on Day 1 to Day 9 and oral casopitant 150 mg on Day 4 and 50 mg on Days 5 and 6. There will be a 14-day washout period between treatment periods 1 and 2.
Intervention: Casopitant 50 mg (Drug)
Outcomes
Primary Outcomes
Plasma levels of casopitant and ketoconazole will be checked on Day 4 to 9 in Cohort 1.
Time Frame: Day 4 to 9 in Cohort 1.
Plasma levels of casopitant will be checked on Day 2 to 4 of Period 1 and
Time Frame: Day 2 to 4 of Period 1
casopitant and ketoconazole will be checked on Day 4 to 9 of Period 2.
Time Frame: Day 4 to 9 of Period 2
Secondary Outcomes
- Safety is evaluated in Cohort 1 by: - Clinical Lab Tests & Physical Exam at Screen, Day -1 & Followup (FU)(at Screen, Day -1 & Followup (FU))
- - Adverse Events Monitoring starting at Day 1(Day 1)
- - 12 lead ECGs at Screen & FU(at Screen & FU)
- - Vitals Signs monitored at Screen, Day -1, 4-7 and FU(at Screen, Day -1, 4-7 and FU)