a study of azd8233 in participants with dyslipidemia.

Conditions: Dyslipidemia

Summary: 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.

Eligibility criteria:
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 \ 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 \ 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 \ 100 beats per minute * uncontrolled hypertension defined as sitting sbp \> 140 mmhg or dbp \> 90 mmhg

Keywords: azd8233 efficacy pk pd immunogenicity safety tolerability