A Phase I, Open Interaction Study Between GLPG1837 and Midazolam in Healthy Male Subjects

Study Overview
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Brief Summary
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This will be a drug-drug interaction study to evaluate the effect of multiple oral doses of GLPG1837 on the single dose pharmacokinetic profile of midazolam administered in fed healthy male subjects. Each subject will receive a single oral dose of midazolam (2 mg) on 2 occasions: on Day 1, before dosing with GLPG1837 and on Day 12 co-administered with GLPG1837, after multiple oral doses of GLPG1837 (daily for 10 days, from Day 2 until Day 11). Also, the safety and tolerability of multiple oral doses of GLPG1837 co-administered with midazolam in healthy male subjects will be evaluated. A first dose group of 12 subjects will receive a total daily dose of 500 mg (250 mg b.i.d.) GLPG1837 and a second dose group of 12 subjects will receive a total daily dose of 1000 mg (500 mg b.i.d.) GLPG1837.

Official Title
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A Phase I, Open Interaction Study Between Oral Doses of GLPG1837 and Single Doses of Midazolam in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: GLPG1837 500 mg
* Drug: Midazolam
* Drug: GLPG1837 1000 mg


Participation Criteria
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Eligibility Criteria
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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
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midazolam and 500 mg GLPG1837<br>Each subject will receive a single oral dose of midazolam (2 mg) on 2 occasions (Days 1 and 12) and multiple oral doses of GLPG1837 (250 mg b.i.d daily for 10 days) from Days 2 to 11. | Drug: GLPG1837 500 mg<br>* Each subject will receive multiple oral daily doses of GLPG1837 (250 mg b.i.d. for 11 days) from Days 2 to 12.<br>Drug: Midazolam<br>* Each subject will receive a single oral dose of midazolam (2 mg) on 2 occasions (Days 1 and 12).<br>|
| Experimental: Midazolam and 1000 mg GLPG1837<br>Each subject will receive a single oral dose of midazolam (2 mg) on 2 occasions (Days 1 and 12) and multiple oral doses of GLPG1837 (500 mg b.i.d daily for 11 days) from Days 2 to 12. | Drug: Midazolam<br>* Each subject will receive a single oral dose of midazolam (2 mg) on 2 occasions (Days 1 and 12).<br>Drug: GLPG1837 1000 mg<br>* Each subject will receive multiple oral doses of GLPG1837 (500 mg b.i.d. for 11 days) from Days 2 to 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum observed concentration (Cmax) of (1'-OH) Midazolam in plasma before and after multiple oral doses of GLPG1837 | To characterize the maximum observed concentration (Cmax) of (1'-OH) Midazolam in plasma over time before and after multiple doses of GLPG1837 in healthy male subjects | Between Day 1 (predose) and Day 13 (24h post last dose on Day 12) | 
| The time of occurrence of Cmax (tmax) of (1'-OH) Midazolam in plasma before and after multiple oral doses of GLPG1837 | To characterize the time of occurrence of Cmax (tmax) of (1'-OH) Midazolam in plasma before and after multiple doses of GLPG1837 in healthy male subjects | Between Day 1 (predose) and Day 13 (24h post last dose on Day 12) | 
| The area under the plasma concentration versus time curve (AUC) of (1'-OH) Midazolam before and after multiple oral doses of GLPG1837 | To characterize the area under the plasma concentration versus time curve (AUC) of (1'-OH) Midazolam before and after multiple doses of GLPG1837 in healthy male subjects | Between Day 1 (predose) and Day 13 (24h post last dose on Day 12) | 
| The apparent terminal half-life (t1/2) of (1'-OH) Midazolam in plasma before and after multiple oral doses of GLPG1837 | To characterize the apparent terminal half-life (t1/2) of (1'-OH) Midazolam in plasma before and after multiple doses of GLPG1837 in healthy male subjects | Between Day 1 (predose) and Day 13 (24h post last dose on Day 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum observed concentration (Cmax) of GLPG1837 (metabolite) in plasma after multiple oral doses of GLPG1837 (and co-administration of Midazolam on Day 12) | To characterize the maximum observed concentration (Cmax) of GLPG1837 (metabolite) in plasma after multiple doses of GLPG1837 (and co-administration of Midazolam on Day 12) in healthy male subjects | Between Day 5 (predose) and Day 14 (48h after the last dose on Day 12) | 
| Number of adverse events | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of the number of adverse events reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| Changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of changes in vital signs as measured by heart rate, blood pressure, respiratory rate and oral body temperature reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| Changes in 12-lead ECG measures | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of changes in 12-ECG measures reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| Changes in physical exam measures | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of changes in physical examination reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| Changes in blood safety lab parameters | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of changes in blood safety lab parameters reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| Changes in urine safety lab parameters | To evaluate the safety and tolerability of GLPG1837 after multiple oral doses in healthy male subjects with or without coadministration of Midazolam in terms of changes in urine safety lab parameters reported | Between Screening and 7-10 days after the last dose of GLPG1837 on Day 12 | 
| The time of occurrence of Cmax (tmax) of GLPG1837 (metabolite) in plasma after multiple oral doses of GLPG1837 (and co-administration of Midazolam on Day 12) | To characterize the time of occurrence of Cmax (tmax) of GLPG1837 (metabolite) in plasma after multiple doses of GLPG1837 (and co-administration of Midazolam on Day 12) in healthy male subjects | Between Day 5 (predose) and Day 14 (48h after the last dose on Day 12) | 
| The area under the plasma concentration versus time curve (AUC) of GLPG1837 (metabolite) in plasma after multiple oral doses of GLPG1837 (and co-administration of Midazolam on Day 12) | To characterize the area under the plasma concentration versus time curve (AUC) of GLPG1837 (metabolite) in plasma after multiple doses of GLPG1837 (and co-administration of Midazolam on Day 12) in healthy male subjects | Between Day 5 (predose) and Day 14 (48h after the last dose on Day 12) | 
| The apparent terminal half-life (t1/2) of GLPG1837 (metabolite) in plasma after multiple oral doses of GLPG1837 (and co-administration of Midazolam on Day 12) | To characterize the apparent terminal half-life (t1/2) of GLPG1837 (metabolite) in plasma after multiple doses of GLPG1837 (and co-administration of Midazolam on Day 12) in healthy male subjects | Between Day 5 (predose) and Day 14 (48h after the last dose on Day 12) | 
| The metabolite to GLPG1837 ratios in plasma after multiple oral doses of GLPG1837 (and co-administration of Midazolam on Day 12) | To characterize the metabolite to GLPG1837 ratios in plasma after multiple doses of GLPG1837 (and co-administration of Midazolam on Day 12) in healthy male subjects | Between Day 5 (predose) and Day 14 (48h after the last dose on Day 12) |