Healthy Volunteer/DDI StudyPhase 1NCT04478513
A Study to Assess the Effect of Fluvoxamine and Smoking on Pharmacokinetics ( the Movement of Drugs Within the Body) of AZD4635 in Healthy Volunteers
A Phase 1 study testing AZD4635 and Fluvoxamine in people with Healthy Volunteer/DDI Study, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
This study is a Phase I, open-label, non-randomized, 2-period, fixed-sequence study in healthy volunteers who are either smokers or non-smokers, performed at a single Clinical Unit. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteer/DDI Study
- What is being tested?
- AZD4635 and Fluvoxamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jul 2020to 23 Dec 2020
- 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
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects of non-childbearing potential subjects aged 18 - 55 years (inclusive at screening) with suitable veins for cannulation or repeated venipuncture.
- Have a body mass index (BMI) between 18.5 and 32.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive.
- Willingness and ability to comply with study and follow-up procedures.
- Subjects who are recruited as non-smokers should have no history of smoking cigarettes for >6 months and test negative for urine cotinine levels at screening and admission.
- Subjects who are recruited as smokers must have a history of smoking >10 cigarettes/day for >6 months and have urine cotinine levels over 500 ng/ml at screening and admission.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of cardiac disease; concurrent electroconvulsive therapy, diabetes mellitus, epilepsy, bleeding disorders (especially GI bleeding), mania and susceptibility to angle-closure glaucoma.
- Presence of refractory nausea and vomiting or chronic GI diseases.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the PI (based on laboratory parameters).
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- Any clinically significant abnormal findings in vital signs at screening as judged by the PI.
- Systolic blood pressure (BP) >140 and/or diastolic BP > 90 mmHg, or history of hypertension at screening.
- Any confirmed clinically significant abnormalities on 12-lead ECG at screening, as judged by the PI.
- Haemoglobin A1c (HbA1c) >5.7% at the screening visit.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies.
- Known or suspected history of drug abuse, within the past 2 years, as judged by the PI.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study.
- Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI.
- Positive screen for drugs of abuse at screening or admission to the study centre.
- Use of herbal preparations/medications within 14 days prior to the administration of the first dose of AZD4635.
- Subject who has had prescription or non-prescription drugs or other products known to be sensitive to Breast cancer resistance protein.
- Use of any prescribed or non prescribed medication including antacids, analgesics, herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP.
- Subjects who have involvement with AstraZeneca or Parexel or are study site employee or their close relatives.
- Subjects who have previously been enrolled in this study or have previously received AZD4635.
- Judgment by the PI that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions, and requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Open-label, Non-randomised Study to Assess the Effect of Fluvoxamine (CYP1A2 Inhibitor) and Smoking (CYP1A2 Inducer) on the Pharmacokinetics of a Single Oral Dosing of AZD4635 in Healthy Volunteers
This study is a Phase I, open-label, non-randomized, 2-period, fixed-sequence study in healthy volunteers who are either smokers or non-smokers, performed at a single Clinical Unit.
Read the detailed description
The study will comprise:
- A screening period of up to 28 days;
- Two treatment periods lasting a total of 17 days from admission to the Clinical Unit (Day -1) to discharge (Day 16). During each treatment period subjects will receive a single dose of AZD4635 under fasting conditions. Period 1 is designed to evaluate the pharmacokinetics (PK) of AZD4635 in healthy smokers and non-smokers. Period 2 is designed to evaluate the effect of fluvoxamine on the PK of AZD4635 in healthy smokers and non-smokers.
- A follow-up call will take place between 6 to 9 days after the last dose of fluvoxamine, to ensure the well-being of the subjects. Completion of the last follow-up call or unscheduled follow-up visit will be considered the end of the study.
Each subject will be involved in the study for a maximum of 53 days.
- Conditions
- Healthy Volunteer/DDI Study
- Being tested
- AZD4635, Fluvoxamine
- Keywords
- CYP1A2 Inhibitor, CYP1A2 Inducer, Pharmacokinetics, Adenosine 2A receptor (A2AR) antagonist
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4635Drug
During each treatment period subjects will receive a single dose of AZD4635 under fasting conditions.
FluvoxamineDrug
Daily oral single doses of fluvoxamine are planned to be administered to healthy volunteers in Treatment Period 2.
| Study group | Role | What they receive |
|---|---|---|
| Smokers | Experimental | Pre-specified group of participants. Receives: Drug: AZD4635; Drug: Fluvoxamine |
| Non-smokers | Experimental | Pre-specified group of participants. Receives: Drug: AZD4635; Drug: Fluvoxamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve from time zero to infinity (AUC)
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
Measured: Days 1-6 and Days 11-16
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
Measured: Days 1-6 and Days 11-16
Maximum observed plasma concentration (Cmax)
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
Measured: Days 1-6 and Days 11-16
Secondary outcomes (1)
Number of subjects with adverse events, serious adverse events and deaths
To assess adverse events as a variable of safety and tolerability of AZD4635 when dosed with and without fluvoxamine in smokers and non-smokers
Measured: From Screening upto Day 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start21 Jul 2020
- Primary completion23 Dec 2020
- Study completion23 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Volunteer/DDI StudyStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study is two-period, fixed sequence study in healthy volunteers who are either smokers or non-smokers. Twenty-eight subjects are planned to be enrolled; 14 subjects who are smokers and 14 subjects who are non-smokers. Enrolling 28 subjects will ensure that at least 12 subjects each from the smoking and the non-smoking populations are evaluated in this study.
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Pablo Forte Soto, Dr., Principal investigator, Parexel Early Phase Clinical Unit London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04478513
- Sponsor's protocol ID
- D8730C00007
- Status last verified
- Jan 2021
- First submitted
- 17 Jul 2020
- Last updated
- 6 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Non-randomised Study to Assess the Effect of Fluvoxamine (CYP1A2 Inhibitor) and Smoking (CYP1A2 Inducer) on the Pharmacokinetics of a Single Oral Dosing of AZD4635 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04478513
- Acronym / sponsor ID
- D8730C00007
- Conditions
- Healthy Volunteer/DDI Study
- Keywords
- CYP1A2 Inhibitor, CYP1A2 Inducer, Pharmacokinetics, Adenosine 2A receptor (A2AR) antagonist
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 21 Jul 2020 (actual)
- Primary completion
- 23 Dec 2020 (actual)
- Study completion
- 23 Dec 2020 (actual)
- First posted
- 20 Jul 2020 (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.
This study is a Phase I, open-label, non-randomized, 2-period, fixed-sequence study in healthy volunteers who are either smokers or non-smokers, performed at a single Clinical Unit.
Detailed description
The study will comprise:
- A screening period of up to 28 days;
- Two treatment periods lasting a total of 17 days from admission to the Clinical Unit (Day -1) to discharge (Day 16). During each treatment period subjects will receive a single dose of AZD4635 under fasting conditions. Period 1 is designed to evaluate the pharmacokinetics (PK) of AZD4635 in healthy smokers and non-smokers. Period 2 is designed to evaluate the effect of fluvoxamine on the PK of AZD4635 in healthy smokers and non-smokers.
- A follow-up call will take place between 6 to 9 days after the last dose of fluvoxamine, to ensure the well-being of the subjects. Completion of the last follow-up call or unscheduled follow-up visit will be considered the end of the study.
Each subject will be involved in the study for a maximum of 53 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study is two-period, fixed sequence study in healthy volunteers who are either smokers or non-smokers. Twenty-eight subjects are planned to be enrolled; 14 subjects who are smokers and 14 subjects who are non-smokers. Enrolling 28 subjects will ensure that at least 12 subjects each from the smoking and the non-smoking populations are evaluated in this study.
| Arm | Type | Receives |
|---|---|---|
| Smokers | Experimental | Drug: AZD4635, Drug: FluvoxaminePre-specified group of participants. |
| Non-smokers | Experimental | Drug: AZD4635, Drug: FluvoxaminePre-specified group of participants. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female subjects of non-childbearing potential subjects aged 18 - 55 years (inclusive at screening) with suitable veins for cannulation or repeated venipuncture.
- Have a body mass index (BMI) between 18.5 and 32.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg, inclusive.
- Willingness and ability to comply with study and follow-up procedures.
- Subjects who are recruited as non-smokers should have no history of smoking cigarettes for >6 months and test negative for urine cotinine levels at screening and admission.
Key exclusion criteria (22 listed)
- History of any clinically significant disease or disorder which, in the opinion of the principal investigator (PI), may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of cardiac disease; concurrent electroconvulsive therapy, diabetes mellitus, epilepsy, bleeding disorders (especially GI bleeding), mania and susceptibility to angle-closure glaucoma.
- Presence of refractory nausea and vomiting or chronic GI diseases.
- Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
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 |
|---|---|---|
| AZD4635During each treatment period subjects will receive a single dose of AZD4635 under fasting conditions. | Drug | Non-smokers, Smokers |
| FluvoxamineDaily oral single doses of fluvoxamine are planned to be administered to healthy volunteers in Treatment Period 2. | Drug | Non-smokers, Smokers |
Primary outcome
Area under the plasma concentration-time curve from time zero to infinity (AUC)
Time frame: Days 1-6 and Days 11-16
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC0-t)
Time frame: Days 1-6 and Days 11-16
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
Maximum observed plasma concentration (Cmax)
Time frame: Days 1-6 and Days 11-16
To assess the effect of fluvoxamine and smoking on the PK of AZD4635 following single oral dosing in healthy volunteers
1 secondary outcome
Number of subjects with adverse events, serious adverse events and deaths
Time frame: From Screening upto Day 24
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 6 Jan 2021.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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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.
Pablo Forte Soto, Dr. principal investigator
Parexel Early Phase Clinical Unit London
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 AZD4635 and Fluvoxamine in people with Healthy Volunteer/DDI Study, run by AstraZeneca 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 6 inclusion and 22 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 6 Jan 2021. 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?
Area under the plasma concentration-time curve from time zero to infinity (AUC) (time frame: Days 1-6 and Days 11-16). The study lists 3 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 6 Jan 2021.