A Study to Assess the Safety and Interaction Between Casopitant and Ketoconazole When Taken By Healthy Adults

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Nausea and Vomiting, Chemotherapy-Induced

Treatments: Drug: Casopitant 150 mg; Drug: Casopitant 150 mg matching placebo; Drug: Casopitant 50 mg matching placebo; Drug: Ketoconazole; Drug: Casopitant 50 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00460707

NKV109990

Details and patient eligibility

About

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.

Enrollment: 85 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

85 participants in 3 patient groups, including a placebo group

Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: Casopitant 50 mg

Drug: Ketoconazole

Drug: Casopitant 150 mg

Cohort 2, Group A

Placebo Comparator group

Description:

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.

Treatment:

Drug: Casopitant 50 mg matching placebo

Drug: Ketoconazole

Drug: Casopitant 150 mg matching placebo

Cohort 2, Group B

Experimental group

Description:

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.

Treatment:

Drug: Casopitant 50 mg

Drug: Ketoconazole

Drug: Casopitant 150 mg