A 2-part drug-drug interaction study of ABX464 in healthy volunteers
Research type
Research Study
Full title
A two part, fixed-sequence, open-label crossover study to evaluate potential CYP1A2-mediated drug-drug interactions of ABX464 in healthy subjects using caffeine and fluvoxamine as probe drugs.
IRAS ID
290513
Contact name
Annelize Koch
Contact email
Sponsor organisation
Abivax S.A.
Eudract number
2020-004879-40
ISRCTN Number
NCT05121714
Clinicaltrials.gov Identifier
.
Duration of Study in the UK
0 years, 4 months, 6 days
Research summary
Research Summary\n\nThe purpose of this study is to investigate the study drug ABX464.\n\nThe objectives are: - To evaluate the effects and interactions of ABX464 with caffeine following administration of caffeine with and without ABX464 (Part A).- To determine how ABX464 is broken down in the body based on how the concentration of ABX464 in the blood differs when it is taken with and without fluvoxamine (a type of anti-depressant medication used to treat obsessive compulsive disorder (OCD)) (Part B).- To provide further safety information on ABX464. This study is a drug-drug interaction study. This means giving drugs which have known effects and a known method of breakdown in the body and then giving the study drug (ABX464) to determine if there is any interaction between the drugs in the body. In Part A, ABX464 will be given at a strength of 50 milligrams (mg) as a single dose once daily for 14 days. A single dose of 50 mg caffeine oral tablet will also be given on Days 1, 4 & 17. In Part B, ABX464 will be given at a strength of 50 mg as a single dose on two separate occasions. Fluvoxamine will be given at the strength of 100 mg tablets once daily for 10 days, then a tapering period of 50 mg tablet once daily for 7 days followed by 25 mg (half of 50 mg tablet) once daily for 7 days.The purpose of this is to support the study sponsor in developing guidance as to how the ABX464 product should be administered in future clinical studies of the product and to understand any potential drug-drug interactions.The study will be conducted in 60 healthy volunteers (males and females) at Simbec-Orion Clinical Pharmacology Unit in Merthyr Tydfil, South Wales. \n\nSummary of Results\n\nThe purpose of this study was to investigate the study drug ABX464. The overall objectives of the study were as follows:\n\n- To evaluate the potential effects and interactions of ABX464 with caffeine following administration of caffeine with and without ABX464 (Part A).\n\n- To determine how ABX464 is metabolised (broken down in the body) based on how the concentration of ABX464 in the blood differs when it was taken with and without fluvoxamine (a type of anti-depressant medication which is used to treat obsessive compulsive disorder (OCD)) (Part B).\n\n- To determine the safety and tolerability (degree to which side effects of a drug can be tolerated) of ABX464 when it was given by itself and when given with caffeine and fluvoxamine (both parts).\n\nThis study was classed as a drug-drug interaction study. This means that participants were administered one of two drugs with known effects and a known method of breakdown (metabolism) in the body (caffeine or fluvoxamine) and then given the study drug (ABX464) to determine if there is any effect or interaction between the drugs in the body and whether administration of caffeine or fluvoxamine affects the safety and tolerability of ABX464. \n\nIn addition, the information gathered in relation to these interactions provided information as to how ABX464 is broken down or metabolised in the body. \n\nThis study was split into 2 separate parts: Part A & Part B. \n\nThe purpose of Part A was to evaluate the safety, tolerability and effects and interactions of ABX464 when it was given with and without caffeine. In Part A, participants were given an oral caffeine tablet on 3 occasions (Day 1, 4 & 17) at a strength of 50 milligrams (mg) and in addition administered ABX464 once daily for a period of 14 days (Day 4-17) at a strength of 50 mg in a capsule form. In Part A, blood samples were taken at set time points throughout the study in order to measure the concentration of caffeine in the blood, how this changed over time and how this changed when participants were taking caffeine and ABX464 at the same time.\n\nThe purpose of Part B was to evaluate the safety, tolerability and effect of fluvoxamine on the concentration of ABX464 in the blood to determine as to whether ABX464 is broken down (metabolised) via the same process as fluvoxamine. In Part B, participants were administered 2 single doses of ABX464 (one on Day 1 and one on Day 11) at a strength of 50 milligrams (mg) per dose in a capsule form in addition to taking a single dose of fluvoxamine once a day for 10 days (Day 2 to 11) at a strength of 100 mg in a tablet form. In Part B, blood samples were taken at set time points throughout the study in order to measure the concentration of ABX464 in the blood, how this changed over time and how this differed with and without fluvoxamine. \n\nThe purpose of this was to support the study sponsor in developing guidance as to how the ABX464 product should be administered in future clinical studies of the product and to develop an understanding as to how ABX464 is metabolised in the body.\n\nWith respect to the safety objectives of the study, it was determined ABX464 was considered to be safe and well tolerated at a 50 mg dose strength, both in the presence and absence of caffeine and fluvoxamine respectively. All adverse events (side effects) which were reported were considered to be mild to moderate in severity and resolved before the study completed.\n\nWith respect to the assessment of the drug-drug interactions of ABX464 and the metabolism, the blood, the following outcomes were reported:\n\n• ABX464 does not demonstrate any drug-drug interactions for drugs which are broken down (metabolised) by the enzyme CYP1A2 as the levels of caffeine and fluvoxamine in the blood remained similar in both the presence and absence of ABX464.\n\n• ABX464 may be metabolised in the same pathway as fluvoxamine, as the levels of ABX464 in the blood showed increases in the presence of fluvoxamine.\n\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
20/WA/0290
Date of REC Opinion
12 Nov 2020
REC opinion
Favourable Opinion