A Study of AZD8233 in Participants With Dyslipidemia. (HAYATE)

December 13, 2024 updated by: AstraZeneca

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
87

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chiyoda-ku, Japan, 1010041
        • Research Site
      • Chuo-ku, Japan, 104-0031
        • Research Site
      • Chuo-ku, Japan, 103-0027
        • Research Site
      • Chuo-ku, Japan, 1040031
        • Research Site
      • Osaka-shi, Japan, 530-0001
        • Research Site
      • Shinjuku-ku, Japan, 160-0008
        • Research Site
      • Suita-shi, Japan, 565-0853
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Part A:Placebo
Placebo solution for subcutaneous injection.
Drug: Part A:Placebo
Placebo solution
Experimental: Part A:AZD8233
AZD8233 for subcutaneous injection.
Drug: Part A:AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Placebo Comparator: Part B:Placebo
Placebo solution for subcutaneous injection.
Drug: Part B:Placebo
Placebo solution
Experimental: Part B:AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
Drug: Part B:AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Experimental: Part B:AZD8233 low dose
AZD8233 low dose for subcutaneous injection.
Drug: Part B:AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Placebo Comparator: Part C: Placebo
Placebo solution for subcutaneous injection.
Drug: Part C: Placebo
Placebo solution
Experimental: Part C: AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
Drug: Part C: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Baseline to week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Measurement at baseline and week 12
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
Baseline to week 12
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
Measurement at baseline and week 12
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
Day 1 and Day 57
Part A & Part C: Cmax of AZD8233
Time Frame: Day 1 and Day 57
Maximum plasma concentration
Day 1 and Day 57
Part A & Part C: t1/2 of AZD8233
Time Frame: Day 1 and Day 57
Terminal half-life
Day 1 and Day 57
Part A & Part C: CL/F (L/h) of AZD8233
Time Frame: Day 1 and Day 57
Apparent plasma clearance
Day 1 and Day 57
Part A & Part C: Vz/F (L)
Time Frame: Day 1 and Day 57
Apparent Volume of distribution during the terminal phase
Day 1 and Day 57

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 20, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 10, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 10, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 1, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D7990C00006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings