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: * 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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
14
Research Site
Harrow, United Kingdom
Area under plasma concentration time curve from zero to infinity (AUCinf) of Midazolam
Effect of AZD4831 on AUCinf of Midazolam will be assessed.
Time frame: 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.
Time frame: 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.
Time frame: Days 1, 2, 11, and 12
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.
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
t½λz of Midazolam and AZD4831 will be assessed.
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
CL/F of Midazolam and AZD4831 will be assessed.
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
Vz/F of Midazolam will be assessed.
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Time frame: 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.
Time frame: Days 2-12
Cmax of AZD4831
Cmax of AZD4831 will be assessed.
Time frame: Days 2-12
Daily pre-dose plasma concentration (CpreD3 up to CpreD10) of AZD4831
Pre-dose plasma concentration of AZD4831 will be assessed.
Time frame: Days 3-10
Plasma concentration 24 hours post the Day 10 dose (C24h) of AZD4831
Plasma concentration of AZD4831 will be assessed.
Time frame: 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.
Time frame: From Screening (Day -28 to Day -2) until Follow-up Visit (Day 20)