Invasive Aspergillosis
Conditions
Keywords
First in man, Antifungal, Intravenous infusion, Healthy volunteers
Brief summary
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.
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.
Interventions
DRUGF901318
Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities. Pharmacokinetic profile
DRUGPlacebo
Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities
Sponsors
Simbec Research
F2G Biotech GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Adverse Events | Single dose | Adverse events will be collected from the time of screening until the final study visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | Single dose | Number of subjects with significant Clinical safety labs and ECG abnormalities as judged by the investigator from screening until final study visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics | Single dose | 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). |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| F901318 0.25 mg/kg Single intravenous infusion over 4 hours
F901318: Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities.
Pharmacokinetic profile | 6 |
| 0.25 mg/kg Placebo Single intravenous infusion over 4 hours
Placebo: Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities | 2 |
| F901318 0.75 mg/kg Single intravenous infusion over 4 hours
F901318: Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities.
Pharmacokinetic profile | 6 |
| Placebo 0.75 mg/kg Single intravenous infusion over 4 hours
Placebo: Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities | 2 |
| F901318 1.5 mg/kg Single intravenous infusion over 4 hours
F901318: Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities.
Pharmacokinetic profile | 6 |
| Placebo 1.5 mg/kg Single intravenous infusion over 4 hours
Placebo: Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities | 2 |
| F901318 3 mg/kg Single intravenous infusion over 4 hours
F901318: Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities.
Pharmacokinetic profile | 6 |
| Placebo 3 mg/kg Single intravenous infusion over 4 hours
Placebo: Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities | 2 |
| F901318 4 mg/kg Single intravenous infusion over 4 hours
F901318: Comparison of adverse events, clinically significant safety laboratory abnormalities and ECG abnormalities.
Pharmacokinetic profile | 6 |
| Placebo 4 mg/kg Single intravenous infusion over 4 hours
Placebo: Comparison of adverse events and clinically sign significant safety lab and ECG abnormalities | 2 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | 0.25 mg/kg Placebo | F901318 0.25 mg/kg | F901318 0.75 mg/kg | Placebo 0.75 mg/kg | F901318 1.5 mg/kg | Placebo 1.5 mg/kg | F901318 3 mg/kg | Placebo 3 mg/kg | F901318 4 mg/kg | Placebo 4 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 2 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 2 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United Kingdom | 40 participants | 2 participants | 6 participants | 6 participants | 2 participants | 6 participants | 2 participants | 6 participants | 2 participants | 6 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 2 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 2 | 1 / 6 | 1 / 2 | 1 / 6 | 0 / 2 | 1 / 6 | 0 / 2 | 1 / 6 | 0 / 2 |
| serious Total, serious adverse events | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 2 |
Outcome results
Primary
Number of Subjects With Adverse Events
Adverse events will be collected from the time of screening until the final study visit
Time frame: Single dose
Population: Full analytical set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F901318 0.25 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| 0.25 mg/kg Placebo | Number of Subjects With Adverse Events | 1 participants |
| F901318 0.75 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| Placebo 0.75 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| F901318 1.5 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| Placebo 1.5 mg/kg | Number of Subjects With Adverse Events | 0 participants |
| F901318 3 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| Placebo 3 mg/kg | Number of Subjects With Adverse Events | 0 participants |
| F901318 4 mg/kg | Number of Subjects With Adverse Events | 1 participants |
| Placebo 4 mg/kg | Number of Subjects With Adverse Events | 0 participants |
Secondary
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
Time frame: Single dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F901318 0.25 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 6 participants |
| 0.25 mg/kg Placebo | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 2 participants |
| F901318 0.75 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 6 participants |
| Placebo 0.75 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 2 participants |
| F901318 1.5 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 6 participants |
| Placebo 1.5 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 2 participants |
| F901318 3 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 6 participants |
| Placebo 3 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 2 participants |
| F901318 4 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 6 participants |
| Placebo 4 mg/kg | Number of Subjects With Significant Clinical Safety Labs and ECG Abnormalities | 2 participants |
Other Pre-specified
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).
Time frame: Single dose