Healthy Volunteers
Conditions
Keywords
Cardiovascular Disease, Drug-drug interaction, Pharmacokinetics, Myeloperoxidase inhibitor, Fixed-sequence
Brief 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 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.
Interventions
DRUGAZD4831
Subjects will receive oral doses once daily from Days 2-11.
DRUGMidazolam
Subjects will receive oral single doses on Day 1 and Day 11.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 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.
Exclusion criteria
* 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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam | 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 | 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 | Days 1, 2, 11, and 12 | Effect of AZD4831 on Cmax of Midazolam will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent volume of distribution based on terminal phase (Vz/F) of Midazolam | Days 1, 2, 11, and 12 | Vz/F of Midazolam will be assessed. |
| Area under the plasma concentration-curve across the dosing interval (AUCtau) of AZD4831 | Days 2-12 | AUCtau of AZD4831 will be assessed. |
| Cmax of AZD4831 | Days 2-12 | Cmax of AZD4831 will be assessed. |
| Time to reach peak or maximum observed concentration or response following drug administration (tmax) of Midazolam and AZD4831 | Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12 | tmax of Midazolam and AZD4831 will be assessed. |
| Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831 | Day 11 | Plasma concentration of AZD4831 will be assessed. |
| Number of patients with adverse events (AE) and serious AEs (SAE) | From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20) | Safety and tolerability of AZD4831 alone and in combination with midazolam will be assessed. |
| Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831 | Days 3-10 | Pre-dose plasma concentration of AZD4831 will be assessed. |
| Half life associated with terminal slope (λz) of a semi logarithmic concentration timecurve (t½λz) of Midazolam and AZD4831 | Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12 | t½λz of Midazolam and AZD4831 will be assessed. |
| Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Midazolam and AZD4831 | Midazolam:Days 1, 2, 11, and 12; AZD4831:Days 2-12 | CL/F of Midazolam and AZD4831 will be assessed. |
Countries
United Kingdom
Outcome results
None listed