A first-in-human study of MTX652 in healthy volunteers
Research type
Research Study
Full title
A multi-part, adaptive Phase 1, first time in human, single centre study in human volunteer subjects to assess safety, tolerability, Pharmacokinetics (PK) of single ascending (SAD) and multiple ascending doses (MAD) of MTX652, including optional study parts to assess effect of food, formulation, potential drug-drug interaction liability and a comparison of elderly versus non-elderly participants.
IRAS ID
1004956
Contact name
Gabrielle Brill
Contact email
Sponsor organisation
Mission Therapeutics Ltd
Eudract number
2021-006764-24
Research summary
Summary of Research\nThe purpose of this study is to investigate the study drug MTX652.\nThe overall objectives are:\n- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of MTX652.\n- To investigate the concentration of MTX652 in the blood, how this changes over a period of time and to evaluate whether there are differences in the concentration in the blood between different dose strengths of MTX652, between single and multiple doses and administration in a healthy volunteer population aged 55 and under vs a healthy volunteer population aged 65 and over. \n- To determine if there are any drug-drug interactions, food or formulation effect for MTX652. \n\nThis study will be split into up to 5 parts. Part 1 and Part 3 will evaluate a single dose of MTX652 administered on one occasion (in healthy volunteers – Part 1 and in an elderly population – Part 3). Part 2 will evaluate a single dose of MTX652 administered as multiple doses twice a day for a maximum period of up to 28 days. Part 4 will evaluate the drug-drug interactions for MTX652 following administration of MTX652 both in the present and absence of itraconazole (ITZ - a drug commonly used in the treatment of different types of fungal infections). Part 5 will evaluate potential effect of food and formulation for MTX652 following administration of MTX652 following an overnight fast and following a high-fat breakfast (food effect) and following administration of MTX652 in the form of an oral solution and solid oral dose.\n\nThe overall study will enrol up to 150 healthy participants and will be conducted at a single research site within the UK.\n\nSummary of Results\nThe purpose of this study was to investigate the study drug MTX652. This study was split into 5 parts and the overall objectives of this study were to determine the safety, tolerability (degree to which side effects of a drug can be tolerated) and concentration in the blood and urine of MTX652 when evaluated in different conditions i.e., different dose strengths, following administration of single and multiple doses, administration in the presence and absence of food, effects of co-administration of other drugs, effects associated with age and effects associated with the formulation (capsule versus suspension) in which MTX652 is administered. The study consisted of 109 participants across the 5 parts of the study; 54 within Part 1, 31 within Part 2 and 24 across Parts 3 to 5.\nBlood and urine samples were taken at set time points throughout the study to measure the concentration profile of MTX652 in the blood and urine, and safety assessments were conducted. The results from each of the groups in each study part have been analysed to determine if there were any significant differences in the safety profile of MTX652, the concentration of MTX652 in the blood and urine between the different groups of the study.\nWith respect to the safety objectives of the study, it was determined that MTX652 was considered to be safe and well tolerated across all dose strengths evaluated during the study (inclusive of up to 200 mg as a single dose and up to 100 mg daily for 14 days) and when administered alone versus in combination with itraconazole. The majority of reported side effects were considered not related to the study drug, were mild in severity and resolved fully without treatment (other than administration of paracetamol where required). One reported side effect in one participant in Part 2 (multiple dose) was classified as severe and resulted in the participant being withdrawn from the study. The event (fainting) was considered to have a possible relationship to the study drug; however the participant fully recovered without treatment. It is also noted that this effect was observed at the lowest dose level evaluated in Part 2 and was not observed in any of the other dose levels evaluated within any other part of the study.\nWith respect to the other objectives of the study the following outcomes were reported:\nFollowing completion of Part 4 (drug-drug interaction with itraconazole) and Part 5 (food/formulation effect), it was observed that there was no notable impact/effect on the levels/exposure of MTX652 when it was given with itraconazole, and no notable effect when it was given as a different formulation (as a capsule) or given with food.\nThe maximum concentrations of MTX652 increased in a manner which was proportional to the dose strength i.e. as the dose strength increased, so did the amount measured in blood samples.\nIn Part 2 of the study where multiple doses of MTX652 were administered, there was no significant effect observed due to accumulation of the drug in the body, and only a small amount of accumulation was seen over 14 days.\nThe levels of MTX652 found in urine were low (<1%), and therefore it was concluded that MTX652 is predominantly eliminated from the body via other routes and not through the kidneys and urine.\nIn 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
22/WA/0045
Date of REC Opinion
15 Feb 2022
REC opinion
Favourable Opinion