Drug-drug Interaction (DDI) Study to Assess Effect of Itraconazole and Rifampicin Upon Olorofim

A Phase I, Open Label Study in Healthy Subjects to Evaluate the Effect of Itraconazole and Rifampicin Upon the Pharmacokinetics of a Single Oral Dose of Olorofim.

This is a Phase 1, single-centre, fixed-sequence, open label, drug-drug interaction study in 2 groups of healthy subjects.

Group A: to evaluate the effects of itraconazole, a strong inhibitor of cytochrome P450 3A (CYP3A), upon the pharmacokinetics of olorofim .

Group B: t o evaluate the effects rifampicin, a strong inducer of CYP3A, upon the pharmacokinetics of olorofim .

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Itraconazole oral solution; Drug: Olorofim; Drug: Rifampicin Oral Capsule

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• males or females of any ethnic origin between 18 and 55 years of age
• subjects weighing between 50 and 100 kg, with a body mass index (BMI) between 18 and 32 kg/m2.
• subjects in good health, as determined by a medical history, physical examination, 12-lead electrocardiogram (ECG) and clinical laboratory evaluations

Exclusion Criteria:

• Female subjects of child-bearing potential.
• Male subjects (or their partners) who are not willing to use appropriate contraception during the study and for 3 months after end of dosing.
• Female subjects who are pregnant or lactating.
• Subjects who have received any prescribed systemic or topical medication within 14 days of first dose administration
• Subjects who have used any non-prescribed systemic or topical medication within 7 days of first dose administration
• Subjects who have received any medications, including St John's Wort, known to chronically alter drug absorption or elimination processes within 30 days of first dose administration
• Subjects with or history of clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatry, respiratory, metabolic, endocrine, ocular haematological or other major disorders as determined by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A; Itraconazole DDI	Drug: Itraconazole oral solution; 200 mg once daily on Days 6 to 15; Drug: Olorofim; Single oral dose on Days 1 and 11; Other Names: F901318
Other: Cohort B; Rifampicin DDI	Drug: Olorofim; Single oral dose on Days 1 and 11; Other Names: F901318; Drug: Rifampicin Oral Capsule; 600 mg once daily on Days 6 to 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
maximum plasma concentration (Cmax) for olorofim.	16 days
Area under the concentration-time curve to time of last quantifiable concentration (AUC0-tlast) for olorofim.	16 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Cmax (Tmax) of olorofim	16 days
area under the concentration-time curve to infinity (AUC0-∞) for olorofim	16 days
terminal elimination half-life (t½) for olorofim	16 days
Number of subjects with treatment-related adverse events	23 days

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: Hammersmith Medicines Research
• Investigators: Principal Investigator: Adeep Puri, Hammersmith Medicines Research

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2019
• Primary Completion (Actual): February 11, 2020
• Study Completion (Actual): February 11, 2020

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 23, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Olorofim
• Other Study ID Numbers: F901318-01-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No