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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: GLPG1837 500 mg; Drug: Midazolam; Drug: GLPG1837 1000 mg

• Study Type: Interventional
• Enrollment (Actual): 24
• 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: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Galapagos NV

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 27, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Estimate): October 23, 2015
• Last Update Submitted That Met QC Criteria: October 21, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: GLPG1837-CL-102; 2015-002517-29 (EudraCT Number)