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

JRCT ID: jRCT2051210041

Registered date:23/06/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Dyslipidemia
• Date of first enrollment: 20/01/2021
• Target sample size: 91
• Study type: Interventional

Intervention(s)

Part A
This is a randomized, single-blind, placebo-controlled, multiple dose Phase 1 study part in
approximately 11 participants with dyslipidemia.

The primary objective of the study is to assess the safety and tolerability of AZD8233 following a multiple subcutaneous dose administration in Japanese patients with dyslipidemia.

The Screening Period starts within 28 days before the randomaization visit and ends on Day-4. Eligible participants will make 8 visits during the treatment period, 1 telephone contact and 8 additional visits during the follow-up period.

They are randomized across 2 different treatment arms in an 8:3 ratio for a 58-day (up to Visit 9) treatment period.

The planned treatment arms are AZD8233 90 mg and placebo. Participants will be dosed
subcutaneously on Days 1, 8, 29, and 57.

Part B
This is a randomized, parallel, double-blind, placebo-controlled, dose-ranging phase 2 study in
approximately 80 participants with dyslipidemia.

The primary objective of the study is to investigate the effect of AZD8233 on LDL-C across different dose levels.

Eligible participants will make 7 visits during the treatment period and 7 additional visits during the follow-up period. They are randomized across 4 different treatment arms in a 1:1:1:1 ratio for a 12-week treatment period.

The planned treatment arms are AZD8233 90 mg SC, AZD8233 50 mg SC, AZD8233 15 mg SC, and placebo SC to be dosed on Days 1, 8, 29, and 57.

Outcome(s)

Primary Outcome

Part A
Adverse events; vital signs, ECG, cardiac telemetry, injection site reaction examinations and clinical laboratory evaluations including platelet count

Part B
Absolute change from baseline in log-transformed LDL-C in serum

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 75age old
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT04823611