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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Drug-drug Interaction Study Between Oral Doses of GLPG1205 and a Cocktail of CYP2C9, CYP2C19 and CYP1A2 Substrates in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: GLPG1205
* Drug: Placebo
* Drug: Cocktail of CYP450 substrates


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG1205 and single CYP450 substrate cocktail dose<br>Daily GLPG1205 administration from Day 1 to Day 12 Single GLPG1205 co-administration on Day 13 with CYP450 substrate cocktail | Drug: GLPG1205<br>* Once daily administration of 2 GLPG1205 capsules from Day 1 to Day 13<br>Drug: Cocktail of CYP450 substrates<br>* Single administration on Day 13 of cocktail of CYP450 substrates: warfarin tablet, omeprazole capsule and caffeine oral solution<br>|
| Placebo Comparator: Placebo and single CYP450 substrate cocktail dose<br>Daily Placebo administration from Day 1 to Day 12 Single Placebo co-administration on Day 13 with CYP450 substrate cocktail | Drug: Placebo<br>* Once daily administration of 2 matching placebo capsules from Day 1 to Day 13<br>Drug: Cocktail of CYP450 substrates<br>* Single administration on Day 13 of cocktail of CYP450 substrates: warfarin tablet, omeprazole capsule and caffeine oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | 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 | 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 | Between Day 13 and 7 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Between Screening and 7 days after the last dosing | 
| Changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature | 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 changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature reported | Between Screening and 7 days after the last dosing | 
| Changes in 12-lead ECG measures | 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 changes in 12-ECG measures reported | Between Screening and 7 days after the last dosing | 
| Changes in physical examination measures | 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 changes in physical examination measures reported | Between Screening and 7 days after the last dosing | 
| Changes in blood safety lab parameters | 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 changes in blood safety parameters reported | Between Screening and 7 days after the last dosing | 
| Changes in urine safety lab parameters | 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 changes in urine safety parameters reported | Between Screening and 7 days after the last dosing |