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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: GLPG1205; Drug: Cocktail of CYP450 substrates

• Registration Number: NCT02623296
• Lead Sponsor: Galapagos NV

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-10
• Study First Submitted: 2015-12-03
• Study First Submitted QC: 2015-12-04
• Study First Posted: 2015-12-07
• Status Verified: 2016-02
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Last Update Submitted: 2016-02-21
• Last Update Posted: 2016-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 14

Inclusion Criteria

• healthy male, age 18-50 years
• BMI between 18-30 kg/m2

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GLPG1205 and single CYP450 substrate cocktail dose	Cocktail of CYP450 substrates	Daily GLPG1205 administration from Day 1 to Day 12 Single GLPG1205 co-administration on Day 13 with CYP450 substrate cocktail
Placebo and single CYP450 substrate cocktail dose	Placebo	Daily Placebo administration from Day 1 to Day 12 Single Placebo co-administration on Day 13 with CYP450 substrate cocktail
Placebo and single CYP450 substrate cocktail dose	Cocktail of CYP450 substrates	Daily Placebo administration from Day 1 to Day 12 Single Placebo co-administration on Day 13 with CYP450 substrate cocktail
GLPG1205 and single CYP450 substrate cocktail dose	GLPG1205	Daily GLPG1205 administration from Day 1 to Day 12 Single GLPG1205 co-administration on Day 13 with CYP450 substrate cocktail

Primary Outcome Measures

Name	Time	Method
The time of occurrence of Cmax (tmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo	Between Day 13 and 7 days after the last dose	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
The area under the plasma concentration versus time curve (AUC) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo	Between Day 13 and 7 days after the last dose	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
The maximum observed concentration (Cmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo	Between Day 13 and 7 days after the last dose	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
The apparent terminal half-life (t1/2) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo	Between Day 13 and 7 days after the last dose	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
The metabolite over parent AUC ratio (R) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo	Between Day 13 and 7 days after the last dose	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

Secondary Outcome Measures

Name	Time	Method
Number of adverse events	Between Screening and 7 days after the last dosing	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
Changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature	Between Screening and 7 days after the last dosing	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
Changes in 12-lead ECG measures	Between Screening and 7 days after the last dosing	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
Changes in physical examination measures	Between Screening and 7 days after the last dosing	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
Changes in blood safety lab parameters	Between Screening and 7 days after the last dosing	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
Changes in urine safety lab parameters	Between Screening and 7 days after the last dosing	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

Trial Locations

Locations (1)

SGS LSS Clinical Pharmacology Unit Antwerp; 🇧🇪 Antwerp, Belgium