A Phase 1 and 2 Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of AZD8233 Following a Multiple Subcutaneous Dose Administration in Japanese Participants With Dyslipidemia (HAYATE)

Completed

Recruitment & Eligibility

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/dLor more 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 or more 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 or more 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 or more 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 randomization, must not be lactating, and must be of nonchild-bearing potential

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

Primary Outcome Measures

Name	Time	Method
Adverse events		Adverse events; vital signs, ECG, cardiac telemetry, injection site reaction examinations and clinical laboratory evaluations including platelet count
Absolute change from baseline in log-transformed LDL-C in serum		Absolute change from baseline in log-transformed LDL-C in serum

Secondary Outcome Measures

Name	Time	Method