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

NCT02623296 | Completed Phase 1

• 2 other identifiers: GLPG1205-CL-1032015-002785-23
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Number of adverse events

  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

  Between Screening and 7 days after the last dosing

• Changes in 12-lead ECG measures

  Between Screening and 7 days after the last dosing

• Changes in physical examination measures

  Between Screening and 7 days after the last dosing

• Changes in blood safety lab parameters

  Between Screening and 7 days after the last dosing

Study Arms (2)

GLPG1205 and single CYP450 substrate cocktail dose

EXPERIMENTAL

Daily GLPG1205 administration from Day 1 to Day 12 Single GLPG1205 co-administration on Day 13 with CYP450 substrate cocktail

Drug: GLPG1205; Drug: Cocktail of CYP450 substrates

Placebo and single CYP450 substrate cocktail dose

PLACEBO COMPARATOR

Daily Placebo administration from Day 1 to Day 12 Single Placebo co-administration on Day 13 with CYP450 substrate cocktail

Drug: Placebo; Drug: Cocktail of CYP450 substrates

Interventions

GLPG1205 DRUG

Once daily administration of 2 GLPG1205 capsules from Day 1 to Day 13

GLPG1205 and single CYP450 substrate cocktail dose

Placebo DRUG

Once daily administration of 2 matching placebo capsules from Day 1 to Day 13

Placebo and single CYP450 substrate cocktail dose

Cocktail of CYP450 substrates DRUG

Single administration on Day 13 of cocktail of CYP450 substrates: warfarin tablet, omeprazole capsule and caffeine oral solution

GLPG1205 and single CYP450 substrate cocktail dose; Placebo and single CYP450 substrate cocktail dose

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (1)

SGS LSS Clinical Pharmacology Unit Antwerp

Antwerp, Antwerp, Belgium

Location

Related Publications (1)

• 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.

  PMID: 33955686 DERIVED

MeSH Terms

Interventions

GLPG1205

Study Officials

• Frédéric Vanhoutte, MD

  Galapagos NV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 7, 2015
• Study Start: October 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 23, 2016

Record last verified: 2016-02

Locations

BE (1)