A Phase 1 and 2 Study of AZD8233 in Participants with Dyslipidemia and this study consists of Part A , Part B and Part C. Part A is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study. Part B is designed as a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study. Part C is designed as a randomized , single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.

Part A: This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.

Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 high dose or placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.

Part B:This is designed as a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study. Approximately 60 Japanese participants will be randomized in a 1:1:1 ratio into 1 of the 4 double-blinded treatment arms; AZD8233 low dose, AZD8233 medium dose, or placebo. Participants will be dosed SC on Days 1, 29, and 57.

Part C:This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.

Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 medium dose or placebo. Participants will be dosed SC on Days 1, 29, and 57.

Key Inclusion Criteria:

Part A

• Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
• Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
• Participants who have fasting triglycerides < 400 mg/dL at screening
• Participants who should be receiving statin therapy
• Participants who should be on stable medication for a certain time period prior to randomization
• Body mass index (BMI) between 19 and 40 kg/m2
• Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential

Part B

• Participants must be 20 to 75 years of age inclusive, at the time of signing the informed consent
• Have a fasting LDL-C ≥ 70 mg/dL but < 190 mg/dL at screening (Visit 2)
• Have fasting triglycerides < 400 mg/dL at screening (Visit 2)
• Should be receiving statin therapy
• LDL-lowering medications should be on stable dosing for ≥ 3 months prior to screening with no planned medication or dose change during study participation
• BMI between 19 and 40 kg/m2
• Female participants must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating, and must not be of childbearing potential

Part C

• Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
• Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
• Participants who have fasting triglycerides < 400 mg/dL at screening
• Participants who should be receiving statin therapy
• Participants who should be on stable medication for a certain time period prior to randomization
• Body mass index (BMI) between 19 and 40 kg/m2
• Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential

Key Exclusion Criteria:

Part A

• eGFR < 60 mL/min/1.73m2 using the Japanese equation
• Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
• History of major bleed or high-risk of bleeding diathesis
• Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
• Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
• Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg

Part B

• eGFR < 40 mL/min/1.73m2 using the Japanese equation at Visit 1
• Poorly controlled type 2 diabetes mellitus (T2DM), defined as Haemoglobin A1c (HbA1c) > 10% at Visit 1
• Acute ischaemic cardiovascular event in the last 12 months prior to randomization
• Heart failure with New York Heart Association (NYHA) Class III-IV
• High-risk of bleeding diathesis as judged by the Investigator
• Uncontrolled hypertension defined as sitting SBP > 160 mmHg or DBP > 90 mmHg at Visit 1 or Visit 3
• Heart rate after 10 minutes sitting rest < 50 bpm or > 100 bpm at Visit 1 or Visit 3

Part C

• eGFR < 60 mL/min/1.73m2 using the Japanese equation
• Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
• History of major bleed or high-risk of bleeding diathesis
• Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
• Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
• Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg

From date of first dose, throughout treatment period and including follow-up period, 24 weeks for Parts A, B and C.

MedDRA 24.1 for Part A, MedDRA 25.0 for Parts B & C

Part A: Single blind Part B: Double blind Part C: Single blind