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Completed

NCT Number: NCT04823611

A Study of AZD8233 in Participants With Dyslipidemia.

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.

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Key information

Age range

20 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Research Site, Chiyoda-ku, Japan

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About this 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Part A:Placebo

Drug

Placebo solution

Part A:AZD8233

Drug

PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Part B:Placebo

Drug

Placebo solution

Part B:AZD8233

Drug

PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Part C: Placebo

Drug

Placebo solution

Part C: AZD8233

Drug

PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Primary outcomes

  1. Part B: Change in LDL-C in Serum at Week 12

    Time frame: Baseline to week 12

    Part B: Change from baseline in LDL-C at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio

Secondary outcomes

  1. Part B: Percentage Change From Baseline in LDL-C in Serum at Week 12

    Time frame: Measurement at baseline and week 12

    Percentage change from baseline to week 12 in Low-density Lipoprotein Cholesterol (LDL-C) in serum

  2. Part B: Change in PCSK9 in Plasma at Week 12

    Time frame: Baseline to week 12

    Part B: Change from baseline in PCSK9 in plasma at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed. Note: log(week 12 data) - log(baseline data) = log(week12/baseline), which is a ratio

  3. Part B: Percentage Change From Baseline in PCSK9 in Plasma at Week 12

    Time frame: Measurement at baseline and week 12

    Percentage change from baseline to week 12 in proprotein convertase subtilisin/kexin type-9 (PCSK9) in plasma

  4. Part A & Part C: AUC (0-24) of AZD8233

    Time frame: Day 1 and Day 57

    Area Under the plasma concentration time curve from time 0 to time 24 hours

  5. Part A & Part C: Cmax of AZD8233

    Time frame: Day 1 and Day 57

    Maximum plasma concentration

  6. Part A & Part C: t1/2 of AZD8233

    Time frame: Day 1 and Day 57

    Terminal half-life

  7. Part A & Part C: CL/F (L/h) of AZD8233

    Time frame: Day 1 and Day 57

    Apparent plasma clearance

  8. Part A & Part C: Vz/F (L)

    Time frame: Day 1 and Day 57

    Apparent Volume of distribution during the terminal phase

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Acronym: HAYATE

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Apr 1, 2021
Registry last updated
Dec 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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