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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.
The study will consist of 2 treatment periods and will comprise:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD4831 | Drug | Subjects will receive oral doses once daily from Days 2-11. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam | Effect of AZD4831 on AUCinf of Midazolam will be assessed. | 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. | 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. | Days 1, 2, 11, and 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Harrow | HA1 3UJ | United Kingdom |
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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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C000706810 | AZD4831 |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Midazolam |
| Drug |
Subjects will receive oral single doses on Day 1 and Day 11. |
|
t½λz of Midazolam and AZD4831 will be assessed. |
| 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. | 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. | 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. | Days 2-12 |
| Cmax of AZD4831 | Cmax of AZD4831 will be assessed. | Days 2-12 |
| Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831 | Pre-dose plasma concentration of AZD4831 will be assessed. | Days 3-10 |
| Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831 | Plasma concentration of AZD4831 will be assessed. | 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. | From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20) |
| D006571 | Heterocyclic Compounds |