F901318 Single Ascending Dose Study in Healthy Male Volunteers

F901318 - A Phase I, Double-Blind, Placebo Controlled, Single Ascending Intravenous Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male Subjects

F901318 is a potent new antifungal agent for the treatment of systemic fungal infections. This study will test it for the first time in man with the objective of assessing its safety, tolerability and pharmacokinetic profile.

Study Overview

• Status: Completed
• Conditions: Invasive Aspergillosis
• Intervention / Treatment: Drug: F901318; Drug: Placebo

Detailed Description

Double blind, placebo controlled, ascending single intravenous dose, sequential group study. Forty subjects will be studied in 5 cohorts (Groups A to E), each group consisting of 8 subjects. Each subject will be on study for approximately 6 weeks. Each subject will participate in one treatment cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 6 (120 hours post-dose). Each cohort will be dosed in a leading edge design in which two subjects will receive study drug (1 active and 1 placebo) on the first dosing day, and the last 6 will receive study drug (active or placebo) on the second dosing day.

All subjects will return for a post-study visit 8 to 10 days after the dose of study medication.

Cohorts will be dosed at 2 weekly intervals. There will be a review of safety and pharmacokinetic data prior to each dose escalation.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Mid Glamorgan
    • Merthyr Tydfil, Mid Glamorgan, United Kingdom, CF48 4DR
      • Simbec Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• 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 60-90 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

Exclusion Criteria:

1. Male subjects who are not, or whose partners are not willing to use appropriate contraception (such as a condom) with established use of oral, injected or implanted hormonal contraceptive, intrauterine device or diaphragm with spermicide for three months after the last dose
2. Subjects who have received any prescribed systemic or topical medication within 14 days of dosing with study drug 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 dosing with study drug (with the exception of vitamin/mineral supplements) 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 dosing with study drug unless in the opinion of the Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety
5. Subjects who are still participating in a clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical or biological entity) in the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: F901318 0.25 mg/kg; Single intravenous infusion over 4 hours	Drug: F901318; Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
Placebo Comparator: 0.25 mg/kg placebo; Single intravenous infusion over 4 hours	Drug: Placebo; Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities
Experimental: F901318 0.75 mg/kg; Single intravenous infusion over 4 hours	Drug: F901318; Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
Placebo Comparator: Placebo 0.75 mg/kg; Single intravenous infusion over 4 hours	Drug: Placebo; Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities
Experimental: F901318 1.5 mg/kg; Single intravenous infusion over 4 hours	Drug: F901318; Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
Placebo Comparator: Placebo 1.5 mg/kg; Single intravenous infusion over 4 hours	Drug: Placebo; Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities
Experimental: F901318 mg/kg; Single intravenous infusion over 4 hours	Drug: F901318; Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
Placebo Comparator: Placebo 3 mg/kg; Single intravenous infusion over 4 hours	Drug: Placebo; Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities
Experimental: F901318 5 mg/kg; Single intravenous infusion over 4 hours	Drug: F901318; Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
Placebo Comparator: Placebo 5 mg/kg; Single intravenous infusion over 4 hours	Drug: Placebo; Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Adverse Events	Adverse events will be collected from the time of screening until the final study visit	Single dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities	Number of subjects with significant Clinical safety labs and ECG abnormalities as judged by the investigator from screening until final study visit	Single dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	Blood samples (6 mL) for analysis of F901318 plasma concentration will be drawn pre-dose and at 1h, 2h, 3h and 4h and then 4.25, 4.5, 5.0, 5.5, 6, 7, 8, 10, 12, 24, 36, 48, 72, 96 and 120 hours following the start of the infusion. (20 samples).	Single dose

Collaborators and Investigators

• Sponsor: F2G Biotech GmbH
• Collaborators: Simbec Research

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 15, 2014
• First Posted (Estimate): May 20, 2014

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: August 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Healthy volunteers; Antifungal; Intravenous infusion; First in man
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Aspergillosis; Anti-Infective Agents; Antifungal Agents; Olorofim
• Other Study ID Numbers: F901318-01-01-14; 2014-000823-25 (EudraCT Number)