Evaluation of the Potential for Cytochrome P450 3A4 Inhibition by F901318 Using Oral Midazolam as a Probe

An Open Label Study in Healthy Volunteers to Evaluate the Potential for Cytochrome P450 3A4 Inhibition by F901318 Using Oral Midazolam as a Probe

Open label evaluation of potential interaction of F901318 with cytochrome P450 3A4 using midazolam as a probe. Twenty healthy male subjects will participate

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: Midazolam with F901318

Detailed Description

This will be an open label study of midazolam (dose 2 mg orally, Day 1) followed by midazolam (2 mg orally) given after dosing with intravenous F901318 4 mg/kg bid for one day followed by 2.5 mg/kg bid for 7 doses (Day 7). Up to twenty subjects will be included in two cohorts which will undergo the same dosing schedules of midazolam and F901318 and undergo the same procedures. The first cohort will consist of 12 subjects studied in two groups of six subjects each. If there is clearly a difference in midazolam kinetics detectable between the first and second doses of midazolam, in this first cohort, the second cohort will not be studied. If there is no clear difference, the second cohort will also be studied to give a final result. PK sampling for midazolam and 1- and 4-hydroxymidazolam plasma and urine concentrations will continue for up to and including 24 hours after dosing with midazolam on both occasions. PK sampling for F901318 will continue from before the first dose and up to 24 hours after the ninth dose. A follow up visit will be conducted 7 +/- 2 days after discharge from the clinical unit following completion of blood sampling following the second dose of midazolam and the ninth dose of F901318.

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

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Subjects will be males of any ethnic origin between 18 and 45 years of age and weighing 60-100 kg inclusive.
2. Subjects must be in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations (congenital non haemolytic hyperbilirubinaemia is acceptable).
3. Subjects will have given their written informed consent to participate in the study and to abide by the study restrictions.
4. Subjects must have ophthalmology assessments within the normal limits at screening. This includes normal Meibomian gland function.

Exclusion Criteria:

1. Male subjects who are not willing to use appropriate contraception during the study and for three months thereafter.
2. Subjects who have received any prescribed systemic or topical medication within 14 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
3. Subjects who have used any non-prescribed systemic or topical medication (including herbal remedies) within 7 days of the dose administration (with the exception of vitamin/mineral supplements and paracetamol) unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
4. Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of the dose administration unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety. For at least 2 weeks prior to dosing and until all blood samples and observations are completed on Day 15 +/- 2s, subjects will not be allowed to eat any food or drink any beverage containing alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family e.g. kale, broccoli, watercress, spring greens, kohlrabi, Brussels sprouts, mustard and charbroiled meats.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midazolam with F901318; Pharmacokinetic profile of midazolam 2 mg orally when given after dosing with F901318 to steady state.	Drug: Midazolam with F901318; Pharmacokinetics of midazolam with F901318

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
area under concentration/time curve	AUC0-24	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability as assessed by number of treatment related adverse events	adverse events	24 hours

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: Hammersmith Medicines Research
• Investigators: Principal Investigator: FRANS VANDENBERG, Hammersmith Medicines Research

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (Estimate): February 12, 2016

Study Record Updates

• Last Update Posted (Estimate): June 9, 2016
• Last Update Submitted That Met QC Criteria: June 8, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; 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; Antifungal Agents; Midazolam; Olorofim
• Other Study ID Numbers: F901318.01.04.15

Plan for Individual participant data (IPD)

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