First-in-Human Single and Multiple Dose of GLPG1690

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: GLPG1690 single ascending doses
* Drug: Placebo single ascending doses
* Drug: GLPG1690, multiple ascending doses, oral suspension
* Drug: Placebo, multiple ascending doses, oral suspension


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 |