A Drug-drug Interaction Study Between GLPG1205 and a Cocktail of CYP450 Substrates in Healthy Male Subjects

Galapagos NV14 enrolled

Overview

This will be a Phase I, randomized, double-blind, placebo-controlled, 2 period cross-over, drug-drug interaction study to evaluate the effect of multiple oral doses of GLPG1205 or placebo (daily from Day 1 to Day 12) on a single dose pharmacokinetic profile of a cocktail of CYP450 substrates administered to healthy male subjects. The cocktail of CYP450 substrates will consist of 10 mg warfarin (CYP2C9 substrate), 20 mg omeprazole (CYP2C19 substrate) and 100 mg caffeine (CYP1A2 substrate). Fourteen healthy male subjects will receive during two treatment periods from Day 1 to Day 12 a daily dose of GLPG1205 or placebo. On Day 13, a single dose of the cocktail of CYP450 substrates will be co-administered either with GLPG1205 or with placebo. The two treatment periods will be separated by a wash-out period of at least 28 days. Also, the safety and tolerability of multiple oral doses of GLPG1205 administered with or without a cocktail of CYP450 substrates in healthy male subjects will be evaluated.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Healthy

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * healthy male, age 18-50 years * BMI between 18-30 kg/m2 Exclusion Criteria: * Poor or moderate metabolizer for CYP2C9 or CYP2C19 as determined by genotyping * Having a contraindication as indicated in the respective Summary of Product Characteristics (or Package Leaflets) for warfarin, omeprazole or caffeine * Intake of nutraceuticals within 3 weeks prior to dosing or within 6 times the elimination half life * Intake of enzyme inducing or enzyme inhibiting drugs within 3 months prior to dosing * Intake of vitamin K within 3 weeks prior to dosing * Any condition that might interfere with the procedures or tests in this study * Drug or alcohol abuse * Smoking

Outcomes

Primary Outcomes

The maximum observed concentration (Cmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo

To characterize the maximum observed concentration (Cmax) of CYP450 substrates in plasma over time after a single dose of a cocktail of CYP450 substrates and multiple doses of GLPG1205 or placebo in healthy male subjects

Time frame: Between Day 13 and 7 days after the last dose

The time of occurrence of Cmax (tmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo

To characterize the time of occurrence of Cmax (tmax) of CYP450 substrates in plasma after a single dose of a cocktail of CYP450 substrates and multiple doses of GLPG1205 or placebo in healthy male subjects

Time frame: Between Day 13 and 7 days after the last dose

The area under the plasma concentration versus time curve (AUC) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo

To characterize the area under the plasma concentration versus time curve (AUC) of CYP450 substrates in plasma after a single dose of a cocktail of CYP450 substrates and multiple doses of GLPG1205 or placebo in healthy male subjects

Time frame: Between Day 13 and 7 days after the last dose

The apparent terminal half-life (t1/2) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo

To characterize the apparent terminal half-life (t1/2) of CYP450 substrates in plasma after a single dose of a cocktail of CYP450 substrates and multiple doses of GLPG1205 or placebo in healthy male subjects

Time frame: Between Day 13 and 7 days after the last dose

The metabolite over parent AUC ratio (R) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo

To characterize the metabolite over parent AUC ratio (R) of CYP450 substrates in plasma after a single dose of a cocktail of CYP450 substrates and multiple doses of GLPG1205 or placebo in healthy male subjects

Time frame: Between Day 13 and 7 days after the last dose

Secondary Outcomes

Number of adverse events

To evaluate the safety and tolerability of GLPG1205 after multiple oral doses in healthy male subjects with or without coadministration of a cocktail of CYP450 substrates in terms of the number of adverse events reported