First-in-Human Single and Multiple Dose of GLPG1837

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 GLPG1837 given to healthy subjects, compared to placebo. Also, the safety and tolerability of multiple ascending oral doses of GLPG1837 given to healthy 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 GLPG1837 and its metabolite present in the blood and urine (pharmacokinetics) will be characterized. The effect of food on the pharmacokinetics of GLPG1837 and its metabolite will also be evaluated. The potential of cytochrome P450 (CYP)3A4 induction after repeated dosing with GLPG1837 will be explored as well.

Official Title
-----------------
Randomized, Double-blind, Placebo-controlled, Dose-escalation Study for the Assessment of Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Oral Doses of GLPG1837 in Healthy Subjects

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

Intervention / Treatment
-----------------
* Drug: GLPG1837 single ascending doses
* Drug: Placebo single dose
* Drug: GLPG1837 multiple ascending doses
* Drug: Placebo multiple doses


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females of non-child bearing potential between 18-50 years of age (included) Subjects must have a body mass index between 18-30 kg/m² (included) Subjects must be judged to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram and laboratory findings Exclusion Criteria: A subject with a known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug Concurrent participation or participation within 8 weeks prior to the initial study drug administration in a drug/device or biologic investigational research study or participation within 15 weeks prior to initial study drug administration in an investigational research study with antibody administration A subject with active drug or alcohol abuse within 2 years prior to the initial study drug administration Current sexually active (and/or child wish) male; a contraception method should be used Pregnant or lactating women or women of childbearing potential

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

Sexes Eligible for Study
-----------------
All

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: GLPG1837 single dose<br>Single oral dose of GLPG1837 suspension - ascending doses | Drug: GLPG1837 single ascending doses<br>* Single dose, oral suspension<br>|
| Placebo Comparator: Placebo single dose<br>Single oral dose of placebo suspension | Drug: Placebo single dose<br>* Single dose, oral suspension matching placebo<br>|
| Experimental: GLPG1837 muliple doses<br>Multiple oral doses of GLPG1837 suspension - ascending doses | Drug: GLPG1837 multiple ascending doses<br>* Multiple doses, daily for 14 days, oral suspension<br>|
| Placebo Comparator: Placebo multiple doses<br>Multiple oral doses of placebo suspension | Drug: Placebo multiple doses<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 GLPG1837 in comparison with placebo after a single oral dose and multiple oral doses 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 GLPG1837 in comparison with placebo after a single oral dose and multiple oral doses 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 GLPG1837 in comparison with placebo after a single oral dose and multiple oral doses 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 GLPG1837 in comparison with placebo after a single oral dose and multiple oral doses in healthy subjects in terms of abnormal electrocardiograms | Between screening and 7-10 days after the last dose | 
| Number of subjects with abnormal physical examination | To evaluate the safety and tolerability of GLPG1837 in comparison with placebo after a single oral dose and multiple oral doses 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 GLPG1837 and its metabolite in plasma | To characterize the amount of GLPG1837 and its metabolite in plasma over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects, fasted or fed | Between Day 1 predose and 48 hours after the (last) dose | 
| The amount of GLPG1837 and its metabolite in urine | To characterize the amount of GLPG1837 and its metabolite in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects, fasted or fed | 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 oral dosing with GLPG1837 by means of the ratio of 6-b-hydroxycortisol/cortisol in urine | Twelve hours before dosing on Day 1 and Day 14 |