The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of AZD0233 following single and multiple ascending dose (SAD and MAD) administration in healthy participants.
This is a Phase I, first time in human, single-blinded, randomized, placebo-controlled study in healthy adult male and female (of non-childbearing potential) participants performed at a single Clinical Unit. The study will be carried out in 2 parts: Part A and Part B. Eight participants will participate in each cohort. Within each cohort, 6 participants will be randomized to receive AZD0233, and 2 participants will be randomized to receive placebo. Part A of the study will be a sequential SAD design. Five dose levels of AZD0233 are planned to be investigated (dose 1 to dose 5), 2 (dose 3 and dose 4) of which will also be assessed in participants of Japanese descent. Part A of the study will comprise: * A Screening Period of maximum 26 days (Day -28 to Day -2). * An inpatient Period of up to 7 days (Day -1 to Day 6): * Cohorts 1A, 2A, 3A (Japanese sub-Cohort only), 4A (including a Japanese sub-Cohort), and 5A: participants will be resident at the Clinical Unit from Day -1 before study intervention administration until Day 4 (72 hours after administration of the study intervention). * Cohort 3A \[food effect (FE)\]: Participants will be resident at the Clinical Unit from Day -1 before study intervention administration and will check-out on Day 6 (72 hours after administration of the study intervention). The impact of food intake on the PK of AZD0233 will be evaluated in the same participants in Cohort 3A after a 24-hour washout period on Day 2. Note: Japanese sub-Cohort from Cohort 3A will not be part of the FE study. • A Follow-up Period of 7 days after the administration of the study intervention which will consist of 1 Follow-up Visit on Day 8 for Cohorts 1A, 2A, 3A (Japanese sub-Cohort only), 4A (including a Japanese sub-Cohort), and 5A and one Follow-up Visit on Day 10 for Cohort 3A, for which participants will return to the Clinical Unit for follow-up assessments. Part B will be a sequential MAD study. Participants will be naïve to AZD0233, i.e., will not have participated in Part A of this study. There will be 3 dose levels in 4 cohorts, including a sub-cohort of participants of Japanese descent at the highest dose. Part B will consist of: * A Screening Period of maximum 26 days (Day -28 to Day -2). * An Inpatient Period of 14 days (Day -1 to Day 13): Participants will be resident at the Clinical Unit from Day -1 before study intervention administration until Day 13 (\>48 hours after administration of the last dose of study intervention in case of QD (once daily) dosing and \>36 hours after the last dose for BID (twice a day) in case of dosing). * A Follow-up Period of 7 days after the administration of the last dose of study intervention which will consist of 2 Follow-up Visits on Day 15 and Day 17.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
84
Randomized participants will receive AZD0233 orally as a single ascending dose (dose 1, dose 2, dose 3, dose 4 or dose 5) or multiple ascending dose (dose 6, dose 7 or dose 8)
Randomized participants will receive matching placebo orally as a SAD or MAD.
Research Site
Glendale, California, United States
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
To assess the safety and tolerability of AZD0233 following oral administration of single ascending doses (Part A) and multiple ascending doses (Part B) and to estimate the maximum tolerated dose (if within pre-defined exposure limits).
Time frame: From screening (Day -28) to follow-up visit (Day 17)
Maximum observed plasma (peak) drug concentration (Cmax) of AZD0233
To characterize the single-dose and steady state pharmacokinetics (PK) of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Area under the concentration-time curve in the dose interval (AUCtau) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Area under plasma concentration time-curve from zero to infinity (AUCinf) of AZD0233
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Terminal elimination half-life (t1/2) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Apparent volume of distribution at steady state following extravascular administration (Vz/F) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Terminal rate constant (λz) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Accumulation ratio for Cmax (Rac Cmax) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Accumulation ratio for AUC (Rac AUC) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Day 1 (Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours), Day 2 (24 hours and 36 hours post-dose) and Day 3 (48 hours post-dose)
Renal clearance (CLR) of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Spot sample at pre-dose and pooled urine at Day 1 (0-3, 3-6, 6-9, 9-12, and 12-24 hours post-dose), Day 2 (24-36 hours post dose) and Day 3 (36-48 hours post-dose).
Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)] of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Spot sample at pre-dose and pooled urine at Day 1 (0-3, 3-6, 6-9, 9-12, and 12-24 hours post-dose), Day 2 (24-36 hours post dose) and Day 3 (36-48 hours post-dose).
Percentage of dose excreted unchanged in urine from time t1 to t2 [Fe(t1-t2)] of AZD0233
To characterize the single-dose and steady state PK of AZD0233 following oral administration of AZD0233 and to assess the impact of food on the single-dose PK of AZD0233 (Dose 3 FE extended cohort in Cohort 3A of Part A).
Time frame: Spot sample at pre-dose and pooled urine at Day 1 (0-3, 3-6, 6-9, 9-12, and 12-24 hours post-dose), Day 2 (24-36 hours post dose) and Day 3 (36-48 hours post-dose).