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

NCT00460707 | Completed Phase 1

• 1 other identifier: NKV109990
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 3

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.

Conditions

Nausea and Vomiting, Chemotherapy-Induced

Keywords

GW679769; healthy adult subjects; casopitant; ketoconazole

Outcome Measures

Primary Outcomes (3)

• Plasma levels of casopitant and ketoconazole will be checked on Day 4 to 9 in Cohort 1.

  Day 4 to 9 in Cohort 1.

• Plasma levels of casopitant will be checked on Day 2 to 4 of Period 1 and

  Day 2 to 4 of Period 1

• casopitant and ketoconazole will be checked on Day 4 to 9 of Period 2.

  Day 4 to 9 of Period 2

Secondary Outcomes (4)

• Safety is evaluated in Cohort 1 by: - Clinical Lab Tests & Physical Exam at Screen, Day -1 & Followup (FU)

  at Screen, Day -1 & Followup (FU)

• - Vitals Signs monitored at Screen, Day -1, 4-7 and FU

  at Screen, Day -1, 4-7 and FU

• - 12 lead ECGs at Screen & FU

  at Screen & FU

• - Adverse Events Monitoring starting at Day 1

  Day 1

Study Arms (3)

Cohort 1

EXPERIMENTAL

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.

Drug: Casopitant 150 mg; Drug: Ketoconazole; Drug: Casopitant 50 mg

Cohort 2, Group A

PLACEBO COMPARATOR

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.

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

Cohort 2, Group B

EXPERIMENTAL

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.

Drug: Casopitant 150 mg; Drug: Ketoconazole; Drug: Casopitant 50 mg

Interventions

Casopitant 150 mg DRUG

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.

Cohort 1; Cohort 2, Group B

Ketoconazole DRUG

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).

Also known as: Casopitant

Cohort 1; Cohort 2, Group A; Cohort 2, Group B

Casopitant 150 mg matching placebo DRUG

Casopitant 150 mg matching placebo will be available as white, film-coated tablets.

Cohort 2, Group A

Casopitant 50 mg DRUG

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.

Cohort 1; Cohort 2, Group B

Casopitant 50 mg matching placebo DRUG

Casopitant 50 mg matching placebo will be available as pale orange, film-coated tablets.

Cohort 2, Group A

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

GSK Investigational Site

Buffalo, New York, 14202, United States

Location

GSK Investigational Site

Columbus, Ohio, 43212, United States

Location

Related 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.

  PMID: 20124517 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

casopitant; Ketoconazole

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 16, 2007
• Study Start: April 16, 2007
• Primary Completion: August 27, 2007
• Study Completion: August 27, 2007
• Last Updated: August 3, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (3)