HealthyPhase 1NCT05121714
Evaluation of the Potential CYP1A2-mediated Drug Drug Interaction Safety, and Tolerability of ABX464
A Phase 1 study testing Caffeine, ABX464 and Fluvoxamine in people with Healthy, run by Abivax S.A. at 1 site in United Kingdom.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Caffeine, ABX464 and Fluvoxamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Dec 2020to 18 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, male or female subject, between 18 and 55 years of age, inclusive.
- Women of childbearing potential (WOCBP) and men receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months (180 days) after end of study or early termination.
- Subject with a body mass index (BMI) of 18.5-30 kilogrammes per square metre (kg/m²).
- No clinically significant history of previous allergy / sensitivity to ABX464 or any of the excipients within the IMP.
- No clinically significant history of previous allergy / sensitivity to caffeine (for Part A) or fluvoxamine (for Part B), or any of the excipients contained within the Non-Investigational Medicinal Product (NIMP).
- No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the Investigational Medicinal Product (IMP)/NIMP.
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- Subject with a negative urinary drugs of abuse (DOA) screen (including alcohol and cotinine) test results, determined within 28 days before the first dose administration of the IMP (N.B.: A positive result may be repeated at the Investigator's discretion).
- Subject with negative human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg)) and hepatitis C virus antibody (HCV Ab) results at Screening.
- No known history of hypertension or abnormal vital signs at screening defined as supine systolic blood pressure (SBP) < 90 or > 140 millimetres of mercury (mmHg), and pulse rate < 40 or > 90 beats per minute (bpm).
- No clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 28 days before first dose of IMP including PR > 220 milliseconds (ms) and QT interval corrected using Fridericia formula (QTcF) >450 ms in males or >470 ms in females, or evidence of clinically significant dysrhythmias (long QT features on ECG, left bundle branch block, or ventricular arrhythmia), atrial fibrillation or history of familial long QT syndromes (Note: partial right bundle branch block is acceptable).
- Subject must be available to complete the study (including all follow up visits/phone call).
- Subject must satisfy an Investigator about their fitness to participate in the study.
- Subject must provide written informed consent to participate in the study
Who cannot join
- Female subject who is pregnant, currently lactating or breastfeeding.
- A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, or any product known to interact with CYP1A2 within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP.
- Subject who has, or who have a relevant history of any clinically significant: neurological, gastrointestinal, renal, hepatic, cardiovascular, vascular, psychiatric, respiratory, metabolic, endocrine, or haematological conditions and/or other significant medical conditions including, without limitation, those pertaining to coronavirus disease 2019 (COVID-19) that, in the opinion of the Investigator or their appropriately qualified designee, would jeopardise the safety of the subject, safety of anyone involved in the study or impact on the validity of the study results.
- A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units for male and female subjects) of alcohol a week) within the past two years.
- Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function).
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- Participation in a New Chemical Entity (NCE) clinical study within 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within 30 days or five half-lives, whichever is longer, before the first dose of IMP (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
- Donation of 450 millilitres (mL) or more blood within the 3 months before the first dose of IMP.
- Users of nicotine products i.e., current smokers or ex-smokers who have smoked within 6 months prior to first dose administration with the study medication or users of cigarette replacements (i.e., e-cigarettes, nicotine patches or gums).
- Total serum bilirubin, alkaline phosphatase (ALP), aspartate transaminase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) and alanine transaminase (ALT) / Serum glutamic pyruvic transaminase (SGPT) > 1.5 x upper limit of normal (ULN).
- Experiences regular headaches (i.e., experiences headaches more than weekly).
- Part B Only:
- Meets Diagnostic and Statistical Manual of Mental Disorders (5th Edition) criteria for moderate or severe substance use disorder within 6 months before Screening.
- Reports having experienced suicidal ideation (Type 4 or 5 on the Columbia-Suicide Severity Rating Scale [C-SSRS]) within 30 days prior to Screening, any suicidal behaviour within 2 years prior to Screening (Any "Yes" answers on Suicidal Behaviour section of C-SSRS), and/or the Investigator assesses the subject to be a safety risk to him/herself or others;
- Clinically significant history of depression or anxiety.
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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
Read the detailed description
This is a Phase 1, 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine) and a known CYP1A2 inhibitor (fluvoxamine). Sixty (60) healthy adult male and female subjects 18 to 55 years of age are planned to participate in the study. Separate cohorts of subjects will be enrolled for Part A (24 subjects) and Part B (36 subjects).
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
This is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine)
ABX464Drug
This is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 inhibitor (fluvoxamine) and a known CYP1A2 substrate (caffeine).
FluvoxamineDrug
his is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 inhibitor (fluvoxamine).
| Study group | Role | What they receive |
|---|---|---|
| Evaluation of CYP1A2 inhibition and induction potential by ABX464 | Other | Using a fixed-sequence crossover study design, the Pharmacokinetics (PK) of caffeine (50 milligrams (mg) single oral dose) will be evaluated in the absence and presence of ABX464 (50 mg once daily for 14 days) in 24 healthy subjects. Caffeine will be administered on Day 1 in the absence of ABX464, on Day 4 simultaneously with ABX464 to evaluate potential CYP1A2 inhibition by ABX464, and on Day 17 simultaneously with ABX464 following 14 days of once daily dosing of ABX464 to evaluate potential CYP1A2 induction by ABX464. Receives: Drug: Caffeine; Drug: ABX464 |
| Evaluation of ABX464 as a substrate for CYP1A2 | Other | Using a fixed-sequence crossover study design, the PK of ABX464 (50 mg single oral dose) will be evaluated in the absence and presence of fluvoxamine (100 mg once daily for 10 days) in 36 healthy subjects. ABX464 will be administered on Day 1 in the absence of fluvoxamine and on Day 11 simultaneously with fluvoxamine following 10 days of once daily dosing of fluvoxamine to evaluate whether ABX464 is a substrate for CYP1A2 Receives: Drug: ABX464; Drug: Fluvoxamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A Evaluate the potential for inhibition and/or induction of CYP1A2 in vivo based on the Peak Plasma Concentration (Cmax) of caffeine (a known CYP1A2 substrate) in the presence and absence of ABX464.
Peak Plasma Concentration (Cmax) for caffeine
Measured: Day 1, Day 4 and Day 17
Part A Evaluate the potential for inhibition and/or induction of CYP1A2 in vivo based on the Area under the plasma concentration versus time curve (AUC) of caffeine (a known CYP1A2 substrate) in the presence and absence of ABX464.
Area under the plasma concentration versus time curve (AUC) for caffeine
Measured: Day 1, Day 4 and Day 17
Part B Evaluate whether ABX464 is a substrate for CYP1A2 in vivo based on Peak Plasma Concentration (Cmax) in the presence and absence of fluvoxamine.
Peak Plasma Concentration (Cmax) for ABX464
Measured: Day 1 and Day11
Part B Evaluate whether ABX464 is a substrate for CYP1A2 in vivo based on Area under the plasma concentration versus time curve (AUC) in the presence and absence of fluvoxamine.
Area under the plasma concentration versus time curve (AUC) for ABX464
Measured: Day 1 and Day 11
Secondary outcomes (1)
Parts A & B • Evaluate the safety and tolerability of ABX464 alone and in the presence of caffeine or fluvoxamine
Incidence of Adverse Events (AEs)
Measured: from baseline up to Day 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2021
- Study start17 Dec 2020
- Primary completion18 May 2021
- Study completion18 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- This is a Phase 1, 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine) and a known CYP1A2 inhibitor (fluvoxamine). Sixty (60) healthy adult male and female subjects 18 to 55 years of age are planned to participate in the study. Separate cohorts of subjects will be enrolled for Part A (24 subjects) and Part B (36 subjects).
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abivax S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Paul Gineste, Study director, Abivax S.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05121714
- Sponsor's protocol ID
- ABX464-902
- Status last verified
- Dec 2021
- First submitted
- 11 Oct 2021
- Last updated
- 5 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05121714
- Acronym / sponsor ID
- ABX464-902
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Abivax S.A.Industry (pharma, biotech, devices)
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 18 May 2021 (actual)
- Study completion
- 18 May 2021 (actual)
- First posted
- 16 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This is a Phase 1, 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine) and a known CYP1A2 inhibitor (fluvoxamine). Sixty (60) healthy adult male and female subjects 18 to 55 years of age are planned to participate in the study. Separate cohorts of subjects will be enrolled for Part A (24 subjects) and Part B (36 subjects).
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a Phase 1, 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine) and a known CYP1A2 inhibitor (fluvoxamine). Sixty (60) healthy adult male and female subjects 18 to 55 years of age are planned to participate in the study. Separate cohorts of subjects will be enrolled for Part A (24 subjects) and Part B (36 subjects).
| Arm | Type | Receives |
|---|---|---|
| Evaluation of CYP1A2 inhibition and induction potential by ABX464 | Other | Drug: Caffeine, Drug: ABX464Using a fixed-sequence crossover study design, the Pharmacokinetics (PK) of caffeine (50 milligrams (mg) single oral dose) will be evaluated in the absence and presence of ABX464 (50 mg once daily for 14 days) in 24 healthy subjects. Caffeine will be administered on Day 1 in the absence of ABX464, on Day 4 simultaneously with ABX464 to evaluate potential CYP1A2 inhibition by ABX464, and on Day 17 simultaneously with ABX464 following 14 days of once daily dosing of ABX464 to evaluate potential CYP1A2 induction by ABX464. |
| Evaluation of ABX464 as a substrate for CYP1A2 | Other | Drug: ABX464, Drug: FluvoxamineUsing a fixed-sequence crossover study design, the PK of ABX464 (50 mg single oral dose) will be evaluated in the absence and presence of fluvoxamine (100 mg once daily for 10 days) in 36 healthy subjects. ABX464 will be administered on Day 1 in the absence of fluvoxamine and on Day 11 simultaneously with fluvoxamine following 10 days of once daily dosing of fluvoxamine to evaluate whether ABX464 is a substrate for CYP1A2 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Healthy, male or female subject, between 18 and 55 years of age, inclusive.
- Women of childbearing potential (WOCBP) and men receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months (180 days) after end of study or early termination.
- Subject with a body mass index (BMI) of 18.5-30 kilogrammes per square metre (kg/m²).
- No clinically significant history of previous allergy / sensitivity to ABX464 or any of the excipients within the IMP.
- No clinically significant history of previous allergy / sensitivity to caffeine (for Part A) or fluvoxamine (for Part B), or any of the excipients contained within the Non-Investigational Medicinal Product (NIMP).
Key exclusion criteria (15 listed)
- Female subject who is pregnant, currently lactating or breastfeeding.
- A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements, or any product known to interact with CYP1A2 within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP.
- Subject who has, or who have a relevant history of any clinically significant: neurological, gastrointestinal, renal, hepatic, cardiovascular, vascular, psychiatric, respiratory, metabolic, endocrine, or haematological conditions and/or other significant medical conditions including, without limitation, those pertaining to coronavirus disease 2019 (COVID-19) that, in the opinion of the Investigator or their appropriately qualified designee, would jeopardise the safety of the subject, safety of anyone involved in the study or impact on the validity of the study results.
- A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units for male and female subjects) of alcohol a week) within the past two years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CaffeineThis is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 substrate (caffeine) | Drug | Evaluation of CYP1A2 inhibition and induction potential by ABX464 |
| ABX464This is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 inhibitor (fluvoxamine) and a known CYP1A2 substrate (caffeine). | Drug | Evaluation of ABX464 as a substrate for CYP1A2, Evaluation of CYP1A2 inhibition and induction potential by ABX464 |
| Fluvoxaminehis is a 2 part, fixed-sequence open-label, crossover study to evaluate the potential CYP1A2-mediated drug-drug interactions (DDI), safety, and tolerability of ABX464 combined with a known CYP1A2 inhibitor (fluvoxamine). | Drug | Evaluation of ABX464 as a substrate for CYP1A2 |
Primary outcome
Part A Evaluate the potential for inhibition and/or induction of CYP1A2 in vivo based on the Peak Plasma Concentration (Cmax) of caffeine (a known CYP1A2 substrate) in the presence and absence of ABX464.
Time frame: Day 1, Day 4 and Day 17
Peak Plasma Concentration (Cmax) for caffeine
Part A Evaluate the potential for inhibition and/or induction of CYP1A2 in vivo based on the Area under the plasma concentration versus time curve (AUC) of caffeine (a known CYP1A2 substrate) in the presence and absence of ABX464.
Time frame: Day 1, Day 4 and Day 17
Area under the plasma concentration versus time curve (AUC) for caffeine
Part B Evaluate whether ABX464 is a substrate for CYP1A2 in vivo based on Peak Plasma Concentration (Cmax) in the presence and absence of fluvoxamine.
Time frame: Day 1 and Day11
Peak Plasma Concentration (Cmax) for ABX464
Part B Evaluate whether ABX464 is a substrate for CYP1A2 in vivo based on Area under the plasma concentration versus time curve (AUC) in the presence and absence of fluvoxamine.
Time frame: Day 1 and Day 11
Area under the plasma concentration versus time curve (AUC) for ABX464
1 secondary outcome
Parts A & B • Evaluate the safety and tolerability of ABX464 alone and in the presence of caffeine or fluvoxamine
Time frame: from baseline up to Day 25
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Gineste study director
Abivax S.A.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Caffeine, ABX464 and Fluvoxamine in people with Healthy, run by Abivax S.A. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A Evaluate the potential for inhibition and/or induction of CYP1A2 in vivo based on the Peak Plasma Concentration (Cmax) of caffeine (a known CYP1A2 substrate) in the presence and absence of ABX464. (time frame: Day 1, Day 4 and Day 17). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2022.