Effects of Repeated Doses of Foliglurax on Drug Metabolizing Enzymes in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to help determine which types of drugs that may interact with foliglurax

Detailed Description
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This study is designed to evaluate the PK of caffeine, montelukast and midazolam following multiple doses of foliglurax in healthy subjects. The study is divided into four periods: Period 1: investigation of the CYP450 probe substrates (caffeine, montelukast, midazolam) alone followed by a 2-day washout before start of Period 2. Period 2: administration of foliglurax for 7 days to reach steady state. Period 3: administration of the CYP450 probe substrates in combination with foliglurax followed by a 7-day washout before start of Period 4. Period 4: investigation of the effects of foliglurax on the PK of the CYP450 probe substrates following washout of foliglurax.

Official Title
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Interventional, Open-label, One-sequence Study to Investigate the Effects of Multiple Doses of Foliglurax on the Pharmacokinetics of Cytochrome P450 (CYP450) Substrates Caffeine (CYP1A2), Montelukast (CYP2C8), and Midazolam (CYP3A4) in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Drug Cocktail
* Drug: Foliglurax
* Drug: midazolam iv


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women with a body mass index (BMI) of ≥ 18.5 and ≤ 30 kg/m2 and a minimum body weight of 60 kg for men and 50 kg for women. Women of child-bearing potential will have a confirmed non-pregnant and non-lactating status. Exclusion Criteria: The subject has a regular intake of more than 500 mg of caffeine per day or impossibility to stop intake, on holidays for example, without headaches forcing to take caffeine again. Other in- and exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Foliglurax<br>Foliglurax, iv midazolam and cocktail of CYP450 probe substrates | Drug: Drug Cocktail<br>* Single oral dose of the cocktail probe substrates (caffeine 200 mg, montelukast 10 mg, midazolam 4 mg)<br>Drug: Foliglurax<br>* Foliglurax<br>Drug: midazolam iv<br>* Single intravenous (iv) dose of midazolam 0.025 mg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf | Area under the plasma concentration-time curve from zero to infinity for midazolam after iv administration and for all oral cocktail probe substrates | Day 1 and 11 for midazolam iv and Day 2,12 and 20 for oral cocktail probe substrates | 
| Cmax | Maximum observed plasma concentration of midazolam after iv administration and for all oral cocktail probe substrates | Day 1 and 11 for midazolam iv and Day 2,12 and 20 for oral cocktail probe substrates |