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

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

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 Overview

• Status: Completed
• Conditions: Nausea and Vomiting, Chemotherapy-Induced
• Intervention / Treatment: Drug: Casopitant 150 mg; Drug: Ketoconazole; Drug: Casopitant 50 mg; Drug: Casopitant 150 mg matching placebo; Drug: Casopitant 50 mg matching placebo

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • GSK Investigational Site
  • New York
    • Buffalo, New York, United States, 14202
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43212
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Drug: 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).; Other Names: Casopitant; Drug: 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.
Placebo Comparator: 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.	Drug: 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).; Other Names: Casopitant; Drug: Casopitant 150 mg matching placebo; Casopitant 150 mg matching placebo will be available as white, film-coated tablets.; Drug: Casopitant 50 mg matching placebo; Casopitant 50 mg matching placebo will be available as pale orange, film-coated tablets.
Experimental: 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.	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.; Drug: 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).; Other Names: Casopitant; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2007
• Primary Completion (Actual): August 27, 2007
• Study Completion (Actual): August 27, 2007

Study Registration Dates

• First Submitted: April 12, 2007
• First Submitted That Met QC Criteria: April 12, 2007
• First Posted (Estimate): April 16, 2007

Study Record Updates

• Last Update Posted (Actual): August 3, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: healthy adult subjects; ketoconazole; GW679769; casopitant
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antiemetics; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Neurokinin-1 Receptor Antagonists; Ketoconazole; Casopitant
• Other Study ID Numbers: NKV109990

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: NKV109990
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register