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
- Conditions
- Dyslipidemia
- Registration Number
- JPRN-jRCT2051210041
- Lead Sponsor
- Hibi Kazushige
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 91
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Part A<br>Adverse events; vital signs, ECG, cardiac telemetry, injection site reaction examinations and clinical laboratory evaluations including platelet count<br><br>Part B<br>Absolute change from baseline in log-transformed LDL-C in serum
- Secondary Outcome Measures
Name Time Method