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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Drug Cocktail; Drug: Foliglurax; Drug: midazolam iv

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • Biotrial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Foliglurax; Foliglurax, iv midazolam and cocktail of CYP450 probe substrates	Drug: Drug Cocktail; Single oral dose of the cocktail probe substrates (caffeine 200 mg, montelukast 10 mg, midazolam 4 mg); Drug: Foliglurax; Foliglurax; Drug: midazolam iv; Single intravenous (iv) dose of midazolam 0.025 mg/kg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 10, 2020
• Primary Completion (ACTUAL): April 3, 2020
• Study Completion (ACTUAL): April 3, 2020

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (ACTUAL): February 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2020
• Last Update Submitted That Met QC Criteria: April 22, 2020
• Last Verified: April 1, 2020

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: 18337A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No