First-in-Human Single and Multiple Dose of GLPG1690

Randomized, Double-blind, Placebo-controlled, Dose-escalation Study for the Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of GLPG1690 in Healthy Male Subjects

The purpose of this First-in-Human study is to evaluate the safety and tolerability after single ascending oral doses of GLPG1690 given to healthy male subjects, compared to placebo. Also, the safety and tolerability of multiple ascending oral doses of GLPG1690 given to healthy male subjects daily for 14 days compared to placebo, will be evaluated.

Furthermore, during the course of the study after single and multiple oral dose administrations, the amount of GLPG1690 present in the blood and urine (pharmacokinetics) as well as the reduction of biomarker levels by GLPG1690 in plasma samples (pharmacodynamics) will be characterized compared to placebo.

The pharmacokinetics of a solid dosage formulation of GLPG1690 will be compared with those of a liquid dosage formulation of GLPG1690.

Also, the potential of cytochrome P450 (CYP)3A4 induction after repeated dosing with GLPG1690 will be explored.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo, multiple ascending doses, oral suspension; Drug: GLPG1690 single ascending doses; Drug: Placebo single ascending doses; Drug: GLPG1690, multiple ascending doses, oral suspension

• Study Type: Interventional
• Enrollment (Actual): 40
• 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:

• 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: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo multiple doses; Multiple oral doses of placebo suspension	Drug: Placebo, multiple ascending doses, oral suspension; Multiple doses, daily for 14 days, oral suspension matching placebo
Experimental: GLPG1690 single dose; Single oral dose of GLPG1690 suspension or solid formulation - ascending doses	Drug: GLPG1690 single ascending doses; Single dose, oral suspension or solid formulation, starting dose of 20mg escalating up to 1500mg
Placebo Comparator: Placebo single dose; Single oral dose of placebo suspension or solid formulation	Drug: Placebo single ascending doses; Single dose, oral suspension or solid formulation matching placebo
Experimental: GLPG1690 multiple doses; Multiple oral doses of GLPG1690 suspension - ascending doses	Drug: GLPG1690, multiple ascending doses, oral suspension; Multiple doses, daily for 14 days, oral suspension, anticipated doses: 300mg to 1000mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events	To evaluate the safety and tolerability of GLPG1690 in comparison with placebo after a single and multiple oral dose in healthy subjects in terms of adverse events	Between screening and 7-10 days after the last dose
Number of subjects with abnormal laboratory parameters	To evaluate the safety and tolerability of GLPG1690 in comparison with placebo after single and multiple oral dose in healthy subjects in terms of abnormal laboratory parameters	Between screening and 7-10 days after the last dose
Number of subjects with abnormal vital signs	To evaluate the safety and tolerability of GLPG1690 in comparison with placebo after a single and multiple oral dose in healthy subjects in terms of abnormal vital signs	Between screening and 7-10 days after the last dose
Number of subjects with abnormal electrocardiogram	To evaluate the safety and tolerability of GLPG1690 in comparison with placebo after a single and multiple oral dose in healthy subjects in terms of abnormal electrocardiogram	Between screening and 7-10 days after the last dose
Number of subjects with abnormal physical examination	To evaluate the safety and tolerability of GLPG1690 in comparison with placebo after a single and multiple oral dose in healthy subjects in terms of abnormal physical examination	Between screening and 7-10 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of GLPG1690 in plasma	To characterize the amount of GLPG1690 in plasma over time - pharmacokinetics (PK) - after a single and multiple oral dose in healthy subjects, either as liquid or solid formulation	Between Day 1 predose and 48 hours after the (last) dose
The amount of GLPG1690 in urine	To characterize the amount of GLPG1690 in urine over time - pharmacokinetics (PK) - after a single and multiple oral dose in healthy subjects, either as liquid or solid formulation	Between Day 1 predose and 24 hours after the (last) dose
Ratio of 6-b-hydroxycortisol/cortisol in urine	To assess the potential of CYP3A4 induction after repeated dosing with GLPG1690 by means of the ratio of 6-b-hydroxycortisol/cortisol in urine	Twelve hours before dosing on Day 1 and Day 14
Levels of biomarker in plasma	To characterize the pharmacodynamics (PD) of GLPG1690 by means of reduction of levels of biomarker by GLPG1690 compared to placebo in plasma after single and multiple oral dose in healthy subjects	Day 1 predose up to 48 hours post (last) dose

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• van der Aar E, Desrivot J, Dupont S, Heckmann B, Fieuw A, Stutvoet S, Fagard L, Van de Wal K, Helmer E. Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials. J Clin Pharmacol. 2019 Oct;59(10):1366-1378. doi: 10.1002/jcph.1424. Epub 2019 Apr 23.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 28, 2014
• First Submitted That Met QC Criteria: June 28, 2014
• First Posted (Estimate): July 1, 2014

Study Record Updates

• Last Update Posted (Estimate): September 22, 2015
• Last Update Submitted That Met QC Criteria: September 20, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: GLPG1690-CL-101; 2014-000981-23 (EudraCT Number)