Clinical trial NCT02623296: A Drug-drug Interaction Study Between GLPG1205 and a Cocktail of CYP450 Substrates in Healthy Male Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2015-12-07
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: The maximum observed concentration (Cmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo
timeFrame: Between Day 13 and 7 days after the last dose
measure: The time of occurrence of Cmax (tmax) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo
timeFrame: Between Day 13 and 7 days after the last dose
measure: The area under the plasma concentration versus time curve (AUC) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo
timeFrame: Between Day 13 and 7 days after the last dose
measure: The apparent terminal half-life (t1/2) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo
timeFrame: Between Day 13 and 7 days after the last dose
measure: The metabolite over parent AUC ratio (R) of CYP450 substrates in plasma after multiple oral doses of GLPG1205 or placebo
timeFrame: Between Day 13 and 7 days after the last dose
Secondary outcomes:
measure: Number of adverse events
timeFrame: Between Screening and 7 days after the last dosing
measure: Changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature
timeFrame: Between Screening and 7 days after the last dosing
measure: Changes in 12-lead ECG measures
timeFrame: Between Screening and 7 days after the last dosing
measure: Changes in physical examination measures
timeFrame: Between Screening and 7 days after the last dosing
measure: Changes in blood safety lab parameters
timeFrame: Between Screening and 7 days after the last dosing
measure: Changes in urine safety lab parameters
timeFrame: Between Screening and 7 days after the last dosing
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: SGS LSS Clinical Pharmacology Unit Antwerp
Study officials:
affiliation: Galapagos NV
name: Frédéric Vanhoutte, MD
role: STUDY_DIRECTOR
References:
citation: 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.