A first in human study of AX-158 in healthy male volunteers
Research type
Research Study
Full title
A Randomised, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, and Pharmacokinetics of AX 158 Following Administration of Single and, Multiple Ascending Oral Doses and Food Effect sub-study in Healthy Male Volunteers.
IRAS ID
295109
Contact name
Annelize Koch
Contact email
Sponsor organisation
Artax Biopharma, Inc.
Eudract number
2021-002541-16
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 9 months, 4 days
Research summary
Summary of Research
The purpose of this study is to investigate AX-158.The objectives of this study are:
- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of AX-158 when it is administered as single and multiple doses at different dose strengths over a period of up to 10 days.- To investigate the concentration of AX-158 in the blood and urine, how this changes over a period of time and to evaluate whether there are differences in the concentration between different dose strengths over time and between single or multiple doses.
- To investigate the effect of food on the concentration of AX-158 in the blood following administration of AX-158 in both a fasted state (without food) and fed state (following a high-fat breakfast).
This study will be split into 3 parts: Part A, B & C.
Part A and Part C will investigate AX-158 when given as a single dose on one occasion (Part A) and a single dose once a day for up to 10 days (Part C) at different dose strengths. Part B will investigate the effect of food on AX-158 following administration in a fasted/fed state. Part A will enrol 5 groups of 8 participants, Part B will enrol 8 participants and Part C will enrol 3 groups of 8 participants.
Blood and urine samples will be taken at set time points throughout the study in order to measure the concentration profile of AX-158.
The results from each of the groups will be compared to determine if there are any differences in the safety of AX-158 and the concentration of AX-158 in the blood and urine, how this changes over time and whether there are any differences between different dose strengths, single and multiple doses and taking the drug with or without food (food effect).Summary of Results
The purpose of this study was to investigate the study drug AX-158.The main objectives of this study were as follows:
- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of AX-158 when it was administered as single and multiple doses at different dose strengths over a period of up to 10 days.
- To investigate the concentration of AX-158 in the blood and urine, how this changed over a period of time and to evaluate whether there were differences in the concentration between different dose strengths over time and between single or multiple doses.
- To investigate the effect of food on the concentration of AX-158 in the blood following administration of AX-158 in both a fasted state (without food) and fed state (following a high-fat breakfast).
As well as evaluating the above, the study also investigated, as exploratory objectives, the effect of AX-158 on the body (known as pharmacodynamics) by analysing the levels of certain biomarkers in the body. Biomarkers are markers within the body such as a molecule or compound expressed by cells in the body, which can be measured and used to identify the presence of a particular biological process occurring in the body or a particular disease.
The study consisted of a total of up to 104 participants for all parts of this study.
For Part A: It was planned that a total of up to 40 participants would be required. Participants were split into 5 groups of up to 8 participants in each group, each evaluating a different dose strength of AX-158 or matching placebo (containing no active drug) starting at 5 milligrams (mg) and increasing to higher strengths in each group.
For Part B: A total of up to 8 participants were required. All participants in Part B will received two single doses of the study drug AX-158 and the dose to be administered in Part B was determined following review of all the data generated in Part A
For Part C: It was planned that a total of up to 24 participants were required. Participants were split into 3 groups of up to 8 participants in each group, each evaluating a different dose strength of AX-158 or matching placebo (containing no active drug)
In this study, all participants were given AX-158 in the form of an oral capsule. Blood and urine samples were taken at set time points throughout the study in order to measure the concentration profile of AX-158 in the blood and urine (urine applied to Part C only). The results were compared from each of the parts of the study to determine if there were any significant differences in the safety profile of AX-158, the concentration of AX-158 in the blood and urine, how this changed over time and whether there were any differences in these factors between different dose strengths and in comparison, to when the drug was administered after a high fat meal or within a fasted state.
The purpose of the data generated in the study provided further information and guidance to support the study sponsor in development of the study drug.
There were no safety concerns following single and multiple ascending doses of AX-158 when administered to healthy participants.
There were no adverse events of note during Part A, Part B or Part C of the study. All adverse events were mild and considered not reasonably possibly related to the study drug. All adverse events were resolved before the study completed without any treatment. Given the low incidence of adverse events during each part of the study, there were no clear treatment or dose related changes/trends in any side effect profile.
There were no serious adverse events, withdrawals due to adverse events or deaths during any part of the study.
There were no clinically significant laboratory safety test results during the study. There were no treatment or dose related changes/trends in any biochemistry, haematology, coagulation, vital signs or 12 lead ECG parameters, with similar values observed following all single and multiple doses of study drug/placebo during all parts of the study.
No participant met any of the study stopping criteria.
The pharmacokinetic data (concentration of study drug in the blood) demonstrated that following both single and multiple oral doses of AX-158, it was rapidly absorbed and showed a gradual decrease in concentration over time.
As the dose of AX-158 was increased from 5mg to 50mg there was a proportional increase in concentration of AX-158 in the blood. The elimination of the drug was well characterised with no changes when drug dose was increased.
Urine Pharmacokinetic data showed that the renal clearance of AX-158 was below standard, suggesting renal reabsorption or other paths of elimination.
Administration of AX-158 following a high fat meal resulted in in a delayed time to reach maximum concentration and lower overall maximum concentration, but similar overall drug exposure over time as compared to administration under fasting conditions. These findings may allow AX-158 to be administered without regard to food intake.
Pharmacokinetic data should be interpreted with caution due to very high variability and small participant numbers per group.
In summary, the data gathered during the study was considered sufficient to meet the objectives of the study and warrant further clinical trials and investigations of the study drug.
REC name
Wales REC 2
REC reference
21/WA/0167
Date of REC Opinion
10 Jun 2021
REC opinion
Favourable Opinion