Single Ascending Oral Dose Study of F901318

Invasive Aspergillosis Clinical Trial

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

Status Completed

Clinical Trial Summary

Double blind, placebo controlled, ascending single oral dose, sequential group study. Forty subjects will complete the study 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 (5 active and 1 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 data, after the first two subjects have been dosed and before dosing of the subsequent six subjects. There will be a complete review of safety and pharmacokinetic data of each cohort prior to each dose escalation.

Clinical Trial Description

Male healthy subjects conforming to the selection criteria will be invited to take part in the study.

Screening visit (Visit 1) After giving fully informed, written consent, subjects will attend the clinic.

Subjects will undergo screening within 28 days prior to the first dose administration. Prior to the screening visit, subjects will:

• Refrain from vigorous exercise for 7 days

• Abstain from alcohol for 48 hours

• Subjects will sign the consent form in the presence of a CRU physician prior to any screening procedures being performed. The information recorded for all subjects, regardless of their suitability for the study, will be retained and archived

The following information and procedures will be recorded and performed as part of the screening assessments:

• Medical history

• Ethnic origin, sex, age, height, weight, and BMI

• Vital signs: supine blood pressure, supine pulse rate, and oral body temperature

• Resting 12 lead ECG

• Physical examination

• Urine drugs of abuse screen, cotinine and breath alcohol

• Fasting clinical laboratory and serology investigations

Up to 28 days after screening, subjects will attend the clinic. Subjects will be admitted to the research unit at approximately 13:00 hours in the afternoon the day before dosing (Day -1; -19 hours pre-dose). Urine will be subjected to a screen for drugs of abuse and there will be a breath test for alcohol and cotinine. Detection of any of these substances will disqualify the subject from the study. A physical examination, check of inclusion/exclusion criteria, clinical laboratory evaluations, oral temperature and body weight will be performed. Subjects will be asked whether they have experienced any adverse events or taken any concomitant medication since their previous visit. Supper will be served starting at 19.30 hours and a snack at 21.00 hours, following which subjects will be fasting. Water will be allowed ad libitum throughout.

On day 1, the total first urine void of the morning for each subject will be collected into a polyethylene container and, from this, a sample will be taken for urinalysis and pre-dose / baseline F901318 concentration. Within one hour before dosing commences (-1 hour), blood will be drawn for laboratory safety assessments (haematology and clinical chemistry), and pre-dose baseline F901318 and metabolites concentration. Supine and standing blood pressure and pulse rate in triplicate, body temperature and a 12-lead ECG will be recorded. The subjects will also be connected to continuous ECG recording from -1 hour until 12 hours after the start of dosing.

Subjects will be asked whether they have experienced any adverse events overnight. Any concomitant medications will be recorded.

Option 1: Subjects will then be dosed. This will be oral ingestion of a liquid formulation followed by 250 mL of water. Subjects will be dosed with regular (at least 5 minute) intervals between each subject.

After initial dosing, the following measurements and observations will be obtained:

• Blood samples for analysis of F901318 plasma concentration will be drawn at 15, 30, 45, 60, 75, 90, 120 minutes, then 3, 4, 6, 8, 10, 12, 18, 24, 36, 48, 72, 96 and 120 hours following dosing. Pharmacokinetic blood samples will be analysed and reviewed before each dose escalation. After the first dose administration, the timing of each blood sample may if necessary be adjusted within the 120-hour period for the subsequent dose escalation. The basis for this decision will depend upon the pharmacokinetic profiles obtained from the preceding group of subjects. All changes will be documented in a file note. The number of samples or volume of blood drawn must not be increased without prior approval of the relevant ethics committee.

Option 2: If it appears from pharmacokinetic measurements that oral absorption is extremely rapid, leading to a high Cmax with a relatively low AUC0-12, the dose may be split in half, with the second half being given 4-8 hours after the first. Under these circumstances, the blood sampling schedule would be decided prior to dosing but would not exceed 26 samples over a 120 hour period.

For Both Options:

• Blood samples for analysis of metabolites will be drawn 4 and 8 hours after initial dosing.

• Blood will be collected for safety measurements (haematology and clinical chemistry) 24, 48 and 72 hours post initial dosing.

• Complete urine collections for analysis of F901318 urine concentration will be made for the following intervals in relation to dosing: 0-4, 4-8, 8-12, 12-16, 16-24, 24-48, 48-72, 72-96 and 96-120 hours after initial dosing.

• Supine and standing pulse rate and blood pressure; and body temperature (vital signs) will be recorded 30, 60 and 120 minutes, 4, 8, 24, 48 and 72 hours after initial dosing.

• Twelve-lead ECGs will be obtained 1, 4, 24, 48 and 72 hours after initial dosing.

• The continuous ECG recording will cease 12 hours after initial dosing.

• Spontaneously reported adverse events will be noted throughout.

• A urine sample will be taken for urinalysis 24, 48 hours and 72 hours after initial dosing.

• Lunch will be served approximately 4 hours after initial dosing but after all the 4 hour observations and blood sampling have been completed and a main meal will be served approximately 8 hours and a snack approximately 12 hours after dosing.

Subjects may leave the Research Unit on Day 6, unless they have experienced adverse events that, in the opinion of the Investigator, warrant further observation and/or treatment.

All subjects will be followed up 8-10 days after dosing with a post-study visit. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aspergillosis
• Invasive Aspergillosis

• NCT number: NCT02394483
• Study type: Interventional
• Source: F2G Ltd.
• Status: Completed
• Phase: Phase 1
• Start date: October 2015
• Completion date: September 2016