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

Nausea and Vomiting, Chemotherapy-Induced Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00460707
• Other study ID #: NKV109990
• Status: Completed
• Phase: Phase 1
• First received: April 12, 2007
• Last updated: August 2, 2017
• Start date: April 16, 2007
• Est. completion date: August 27, 2007

Study information

• Verified date: August 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: August 27, 2007
• Est. primary completion date: August 27, 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nausea and Vomiting, Chemotherapy-Induced
• Vomiting

Intervention

Drug:
• Casopitant 150 mg
Casopitant 150 mg will be available as white, film-coated tablets. Casopitant tablets will be taken with 240 milliliters (mL) of water at room temperature on an empty stomach.
• Ketoconazole
Ketoconazole will be available as 200 mg tablets which will be taken with 240 mL of water on an empty stomach (after a 2 hour fast on Day 4 of Treatment Period 2 and after a 1 hour fast on all other dosing days).
• Casopitant 150 mg matching placebo
Casopitant 150 mg matching placebo will be available as white, film-coated tablets.
• Casopitant 50 mg
Casopitant 50 mg will be available as pale orange, film-coated tablets. Casopitant tablets will be taken with 240 mL of water at room temperature on an empty stomach.
• Casopitant 50 mg matching placebo
Casopitant 50 mg matching placebo will be available as pale orange, film-coated tablets.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma levels of casopitant and ketoconazole will be checked on Day 4 to 9 in Cohort 1.		Day 4 to 9 in Cohort 1.
Primary	Plasma levels of casopitant will be checked on Day 2 to 4 of Period 1 and		Day 2 to 4 of Period 1
Primary	casopitant and ketoconazole will be checked on Day 4 to 9 of Period 2.		Day 4 to 9 of Period 2
Secondary	Safety is evaluated in Cohort 1 by: - Clinical Lab Tests & Physical Exam at Screen, Day -1 & Followup (FU)		at Screen, Day -1 & Followup (FU)
Secondary	- Vitals Signs monitored at Screen, Day -1, 4-7 and FU		at Screen, Day -1, 4-7 and FU
Secondary	- 12 lead ECGs at Screen & FU		at Screen & FU
Secondary	- Adverse Events Monitoring starting at Day 1		Day 1

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 109990 can be found on the GSK Clinical Study Register.