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DyslipidemiaPhase 1/2HAYATENCT04823611

A Study of AZD8233 in Participants With Dyslipidemia.

A Phase 1/2 study testing Part A:AZD8233 and Part B:AZD8233 in people with Dyslipidemia, run by AstraZeneca at 7 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 to 75 years
Conditions the study is for
Dyslipidemia
What is being tested?
Part A:AZD8233 and Part B:AZD8233
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
87 participants
Where
7 sitesJapan
Study dates
20 Jan 2021to 10 Sep 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Japan7 sites

  • Research Site

    Chiyoda-ku, 1010041

  • Research Site

    Chūōku, 103-0027

  • Research Site

    Chūōku, 104-0031

  • Research Site

    Chūōku, 1040031

  • Research Site

    Osaka, 530-0001

  • Research Site

    Shinjuku-ku, 160-0008

  • Research Site

    Suita-shi, 565-0853

Other trials in Japan

About this study

Official 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

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.

Read the 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.

Conditions
Dyslipidemia
Being tested
Part A:Placebo, Part A:AZD8233, Part B:Placebo, Part B:AZD8233, Part C: Placebo
Keywords
AZD8233, Efficacy, PK, PD, Immunogenicity, Safety, Tolerability
Medical subject headings
Dyslipidemias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Part A:PlaceboDrug

    Placebo solution

  • Part A:AZD8233Drug

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

  • Part B:PlaceboDrug

    Placebo solution

  • Part B:AZD8233Drug

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

  • Part C: PlaceboDrug

    Placebo solution

  • Part C: AZD8233Drug

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

Study groups in NCT04823611
Study groupRoleWhat they receive
Part A:PlaceboPlacebo comparatorPlacebo solution for subcutaneous injection.
Receives: Drug: Part A:Placebo
Part A:AZD8233ExperimentalAZD8233 for subcutaneous injection.
Receives: Drug: Part A:AZD8233
Part B:PlaceboPlacebo comparatorPlacebo solution for subcutaneous injection.
Receives: Drug: Part B:Placebo
Part B:AZD8233 medium doseExperimentalAZD8233 medium dose for subcutaneous injection.
Receives: Drug: Part B:AZD8233
Part B:AZD8233 low doseExperimentalAZD8233 low dose for subcutaneous injection.
Receives: Drug: Part B:AZD8233
Part C: PlaceboPlacebo comparatorPlacebo solution for subcutaneous injection.
Receives: Drug: Part C: Placebo
Part C: AZD8233 medium doseExperimentalAZD8233 medium dose for subcutaneous injection.
Receives: Drug: Part C: AZD8233

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline to week 12

Secondary outcomes (8)

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

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

    Measured: Measurement at baseline and week 12

  2. Part B: Change in PCSK9 in Plasma at 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

    Measured: Baseline to week 12

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

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

    Measured: Measurement at baseline and week 12

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

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

    Measured: Day 1 and Day 57

  5. Part A & Part C: Cmax of AZD8233

    Maximum plasma concentration

    Measured: Day 1 and Day 57

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

    Terminal half-life

    Measured: Day 1 and Day 57

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

    Apparent plasma clearance

    Measured: Day 1 and Day 57

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

    Apparent Volume of distribution during the terminal phase

    Measured: Day 1 and Day 57

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study start20 Jan 2021
  3. Primary completion10 Sep 2022
  4. Study completion10 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
87 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04823611
Sponsor's protocol ID
D7990C00006
Acronym
HAYATE
Status last verified
Dec 2024
First submitted
1 Feb 2021
Last updated
24 Dec 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.

    PubMed 38504437

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Part A:AZD8233 and Part B:AZD8233 in people with Dyslipidemia, run by AstraZeneca at 7 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part B: Change in LDL-C in Serum at Week 12 (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04823611, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2024.

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