Validation Study of Multiple Probe Compounds for Drug Interaction Evaluation

Summary

The purpose of this study is to identify and validate a probe cocktail for use in future drug-drug interaction studies. Cytochrome P450 enzymes and transport proteins play important roles in the disposition of drugs. Changes in the activity of these pathways can be assessed using probe drugs selected on the basis of their metabolic or transport pathway. This will be a two part study with the same subjects participating in both parts to decrease variability in data. The purpose of Part 1 is to identify a set of probe drugs ('cocktail') which do not interact with one another; groups of healthy volunteers will receive 7 probe drugs individually and as a combination of the 7 drugs given together as a cocktail. Part 2 will assess the performance of the probe cocktail using three known inhibitors (validation). The inhibitors plus probe cocktail will evaluate the ability of the newly established cocktail to accurately quantify metabolizing enzyme or transporter inhibition, representing a fundamental advance in probe cocktail validation and utility for drug development.

Conditions

• Drug Interactions

Interventions

DRUG

Caffeine

Caffeine dosed at 100 mg as probe for CYP1A2 pathway

DRUG

Rosiglitazone

Dosed at 4 mg as probe for CYP2C8 pathway

DRUG

Flurbiprofen

Dosed at 40 mg, probe for CYP2C9 pathway

DRUG

Omeprazole

Dosed at 20 mg, probe for CYP2C19 pathway

DRUG

Dextromethorphan

Dosed at 30 mg, probe for CYP2D6 pathway

DRUG

Midazolam

Dosed at 3 mg for Part 1, Part 2 cohorts B and C and 1 mg for Part 2 Cohort A, probe drug for CYP3A4/5 pathway

DRUG

Rosuvastatin

Dosed at 10 mg, probe drug for OATP1B1 pathway

DRUG

Ketoconazole

Dosed at 400 mg once-daily Day 1 through Day 9, inhibitor of CYP3A4

DRUG

Fluconazole

Dosed at 400 mg x 1 dose on day 1, 200 mg once daily on days 2 through 9, inhibitor of CYP2C9 pathway

DRUG

Rifampin

Dosed at 600 mg x 1 dose on Day 1 and Day 8, inhibitor of OATP1B1 pathway

DRUG

Rosiglitazone

Dosed at 15 mg, probe drug for CYP2C8 pathway

Sponsors & Collaborators

• GlaxoSmithKline

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · GlaxoSmithKline

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2009-08-26

Primary Completion

2011-08-29

Completion

2011-08-29

Countries

• South Korea

Study Locations