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

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

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 Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: GLPG1205; Drug: Cocktail of CYP450 substrates; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • SGS LSS Clinical Pharmacology Unit Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• Desrivot J, Van Kaem T, Allamassey L, Helmer E. Effect of GLPG1205, a GPR84 Modulator, on CYP2C9, CYP2C19, and CYP1A2 Enzymes: In Vitro and Phase 1 Studies. Clin Pharmacol Drug Dev. 2021 Sep;10(9):1007-1017. doi: 10.1002/cpdd.956. Epub 2021 May 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Estimate): February 23, 2016
• Last Update Submitted That Met QC Criteria: February 21, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: GLPG1205-CL-103; 2015-002785-23 (EudraCT Number)