A Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AZD8965 in Healthy Participants (Including Japanese and Chinese Participants) and an Open-label Cohort to Assess the Effect of Food on the Pharmacokinetics of AZD8965 in Healthy Participants
NCT Number: NCT06502379
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy Participants
Interventions: DRUG: AZD8965|OTHER: Placebo
Sponsor: AstraZeneca
Sex: ALL
Age: ADULT
Enrollment: 163
Study Design: Allocation: RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: DOUBLE (PARTICIPANT, CARE_PROVIDER)|Primary Purpose: TREATMENT
Start Date: 2024-08-02
Completion Date: 2025-08-25
Locations: Research Site, Glendale, California, 91206, United States

Summary:
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of AZD8965 via single and multiple ascending doses in healthy participants (including Japanese and Chinese participants), and to assess the effect of food on the safety, tolerability, and PK of orally administered AZD8965.

Primary Outcome Measures: Parts 1 and 3A: Number of participants with adverse events (AEs) and serious adverse events (SAEs), To assess the safety and tolerability of AZD8965 following oral administration of single ascending doses to healthy participants., SAEs: From Screening (Day -28) to 5 weeks; AEs: From Day 1 to 5 weeks|Parts 2 and 3B: Number of participants with AEs and SAEs, To assess the safety and tolerability of AZD8965 following oral administration of multiple ascending doses to healthy participants., SAEs: From Screening (Day -28) to 8 weeks; AEs: From Day 1 to 8 weeks.|Part 4: Maximum observed drug concentration (Cmax), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Area under concentration-time curve from time 0 to infinity (AUCinf), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Time to reach maximum observed concentration (tmax), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)], To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Terminal elimination half-life (t½λz), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Mean Residence Time (MRTinf), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Apparent total body clearance (CL/F), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Apparent volume of distribution based on the terminal (Vz/F), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Accumulation ratio for AUC (Rac AUC), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Accumulation ratio for Cmax (Rac Cmax), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)], To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 5|Part 4: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)], To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 5|Part 4: Relative bioavailability calculated as test AUC/reference AUC (Frel AUC), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Relative bioavailability calculated as test Cmax/reference Cmax (Frel Cmax), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 7 (72-hour post dose)|Part 4: Renal clearance (CLR), To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 5
Secondary Outcome Measures: Parts 1, 2, 3A and 3B: Maximum observed drug concentration (Cmax), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Area under concentration-time curve from time 0 to infinity (AUCinf), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Time to reach maximum observed concentration (tmax), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)], To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Terminal elimination half-life (t½λz), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Mean Residence Time (MRTinf), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Apparent total body clearance (CL/F), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Apparent volume of distribution based on the terminal (Vz/F), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 1, 2, 3A and 3B: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)], To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9|Parts 1, 2, 3A and 3B: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)], To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9|Parts 1, 2, 3A and 3B: Renal clearance (CLR), To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants., Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9|Parts 2 and 3B: Area under concentration-time curve in the dosing interval (AUCtau), To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 2 and 3B: Accumulation ratio for AUC (Rac AUC), To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 2 and 3B: Accumulation ratio for Cmax (Rac Cmax), To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Parts 2 and 3B: Temporal Change Parameter (TCP), To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants., From Day 1 (pre-dose) to Day 10 (48-hour post dose)|Part 4: Number of participants with AEs and SAEs, To assess the safety and tolerability of AZD8965 under fasted and fed (after intake of a high fat meal) conditions in healthy participants., SAEs: From Screening (Day -28) to 6 weeks; AEs: From Day 1 to 6 weeks