Healthy VolunteersPhase 1NCT05052710
Study to Assess the Effect of AZD4831 on the Pharmacokinetics (Drug Behavior in the Body) of Midazolam
A Phase 1 study testing AZD4831 and Midazolam in people with Healthy Volunteers, run by AstraZeneca at 1 site in United Kingdom.
Trial summary
The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- AZD4831 and Midazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Oct 2021to 29 Nov 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 and/or female subjects with suitable veins for cannulation or repeated venepuncture.
- Males must be willing to use appropriate contraception methods.
- Females must not be lactating and must be of non-childbearing potential, confirmed at Screening.
- Have a body mass index between 18.5 and 30 kg/m^2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.
Who cannot join
- History of any clinically significant disease or disorder.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- A positive Corona Virus Disease 2019 test at Screening or admission to the Clinical Unit on Day -1.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results.
- Any clinically significant abnormal findings in vital signs.
- clinically significant abnormalities on 12-lead electrocardiogram.
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- Any positive result at the Screening Visit for Hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antibody.
- Known or suspected history of drug abuse in the last 2 years.
- Current smokers or those who have smoked or used nicotine products within the 3 months prior to the Screening Visit.
- Known or suspected history of alcohol or drug abuse.
- Use of any prescribed or non-prescribed medication.
- Subjects with acute pulmonary insufficiency, marked neuromuscular respiratory weakness, obsessional states, phobic states, sleep apnoea syndrome, or unstable myasthenia gravis.
- History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigatoror history of hypersensitivity to drugs with a similar chemical structure or class to AZD4831 or midazolam.
- History or ongoing allergy/hypersensitivity to drugs(including but not limited to rash, angioedema, acute urticaria).
- Subjects who, in the opinion of the Investigator, have any clinically significant skin condition.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD4831 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects
The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10 consecutive days.
Read the detailed description
The study will consist of 2 treatment periods and will comprise:
- A Screening period of maximum 28 days;
- Treatment Period 1 and Treatment Period 2:
Treatment Period 1: Midazolam only (Day 1). Treatment Period 2: AZD4831 only (Days 2 to 10, once daily dosing) and AZD4831 plus midazolam (Day 11).
- A final Follow-up Visit after the last administration of investigational medicinal product (IMP) (Day 20 [± 1 day]).
Each subject will be involved in the study for approximately 7 weeks.
- Conditions
- Healthy Volunteers
- Being tested
- AZD4831, Midazolam
- Keywords
- Cardiovascular Disease, Drug-drug interaction, Pharmacokinetics, Myeloperoxidase inhibitor, Fixed-sequence
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4831Drug
Subjects will receive oral doses once daily from Days 2-11.
MidazolamDrug
Subjects will receive oral single doses on Day 1 and Day 11.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Subjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11. Receives: Drug: AZD4831; Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam
Effect of AZD4831 on AUCinf of Midazolam will be assessed.
Measured: Days 1, 2, 11, and 12
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam
Effect of AZD4831 on AUClast of Midazolam will be assessed.
Measured: Days 1, 2, 11, and 12
Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam
Effect of AZD4831 on Cmax of Midazolam will be assessed.
Measured: Days 1, 2, 11, and 12
Secondary outcomes (9)
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831
tmax of Midazolam and AZD4831 will be assessed.
Measured: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831
t½λz of Midazolam and AZD4831 will be assessed.
Measured: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831
CL/F of Midazolam and AZD4831 will be assessed.
Measured: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam
Vz/F of Midazolam will be assessed.
Measured: Days 1, 2, 11, and 12
Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831
AUCtau of AZD4831 will be assessed.
Measured: Days 2-12
Cmax of AZD4831
Cmax of AZD4831 will be assessed.
Measured: Days 2-12
Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831
Pre-dose plasma concentration of AZD4831 will be assessed.
Measured: Days 3-10
Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831
Plasma concentration of AZD4831 will be assessed.
Measured: Day 11
Number of patients with adverse events (AE) and serious AEs (SAE)
Safety and tolerability of AZD4831 alone and in combination with midazolam will be assessed.
Measured: From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2021
- Study start5 Oct 2021
- Primary completion29 Nov 2021
- Study completion29 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05052710
- Sponsor's protocol ID
- D6580C00012
- Status last verified
- Dec 2021
- First submitted
- 14 Sep 2021
- Last updated
- 13 Dec 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 13 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD4831 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT05052710
- Acronym / sponsor ID
- D6580C00012
- Conditions
- Healthy Volunteers
- Keywords
- Cardiovascular Disease, Drug-drug interaction, Pharmacokinetics, Myeloperoxidase inhibitor, Fixed-sequence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2021 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 22 Sep 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.
The study is an open-label, fixed-sequence, cross-over study conducted at a single Clinical Unit to assess the pharmacokinetics (PK) of midazolam in healthy male and female (non-childbearing potential) subjects when administered alone and in combination with AZD4831 after multiple doses (once daily) of AZD4831 for 10 consecutive days.
Detailed description
The study will consist of 2 treatment periods and will comprise:
- A Screening period of maximum 28 days;
- Treatment Period 1 and Treatment Period 2:
Treatment Period 1: Midazolam only (Day 1). Treatment Period 2: AZD4831 only (Days 2 to 10, once daily dosing) and AZD4831 plus midazolam (Day 11).
- A final Follow-up Visit after the last administration of investigational medicinal product (IMP) (Day 20 [± 1 day]).
Each subject will be involved in the study for approximately 7 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: AZD4831, Drug: MidazolamSubjects will receive midazolam on Day 1 and AZD4831 once daily from Days 2 to 10, and AZD4831 plus midazolam on Day 11. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy male and/or female subjects with suitable veins for cannulation or repeated venepuncture.
- Males must be willing to use appropriate contraception methods.
- Females must not be lactating and must be of non-childbearing potential, confirmed at Screening.
- Have a body mass index between 18.5 and 30 kg/m^2 (inclusive) and weigh at least 50 kg and no more than 100 kg (inclusive) at Screening.
Key exclusion criteria (15 listed)
- History of any clinically significant disease or disorder.
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- A positive Corona Virus Disease 2019 test at Screening or admission to the Clinical Unit on Day -1.
- Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results.
- Any clinically significant abnormal findings in vital signs.
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 |
|---|---|---|
| AZD4831Subjects will receive oral doses once daily from Days 2-11. | Drug | Treatment Arm |
| MidazolamSubjects will receive oral single doses on Day 1 and Day 11. | Drug | Treatment Arm |
Primary outcome
Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam
Time frame: Days 1, 2, 11, and 12
Effect of AZD4831 on AUCinf of Midazolam will be assessed.
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) of Midazolam
Time frame: Days 1, 2, 11, and 12
Effect of AZD4831 on AUClast of Midazolam will be assessed.
Maximum observed plasma (peak) drug concentration (Cmax) of Midazolam
Time frame: Days 1, 2, 11, and 12
Effect of AZD4831 on Cmax of Midazolam will be assessed.
9 secondary outcomes
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831
Time frame: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831
Time frame: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831
Time frame: Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12
Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam
Time frame: Days 1, 2, 11, and 12
Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831
Time frame: Days 2-12
Cmax of AZD4831
Time frame: Days 2-12
Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831
Time frame: Days 3-10
Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831
Time frame: Day 11
Number of patients with adverse events (AE) and serious AEs (SAE)
Time frame: From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)
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 13 Dec 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.
The record lists no contact. Use the official record to reach the sponsor.
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 AZD4831 and Midazolam in people with Healthy Volunteers, 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 4 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 13 Dec 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 plasma concentration time curve from zero to infinity (AUCinf) of Midazolam (time frame: Days 1, 2, 11, and 12). 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 13 Dec 2021.