MedDataX Logo

A Study of AZD8233 in Participants With Dyslipidemia.

NCT ID: NCT04823611

Last Updated: 2024-12-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-20

Study Completion Date

2022-09-10

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Dyslipidemia

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

AZD8233 Efficacy PK PD Immunogenicity Safety Tolerability

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel Assignment
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Part A: Single blind Part B: Double blind Part C: Single blind

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part A:Placebo

Placebo solution for subcutaneous injection.

Group Type PLACEBO_COMPARATOR

Part A:Placebo

Intervention Type DRUG

Placebo solution

Part A:AZD8233

AZD8233 for subcutaneous injection.

Group Type EXPERIMENTAL

Part A:AZD8233

Intervention Type DRUG

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

Part B:Placebo

Placebo solution for subcutaneous injection.

Group Type PLACEBO_COMPARATOR

Part B:Placebo

Intervention Type DRUG

Placebo solution

Part B:AZD8233 medium dose

AZD8233 medium dose for subcutaneous injection.

Group Type EXPERIMENTAL

Part B:AZD8233

Intervention Type DRUG

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

Part B:AZD8233 low dose

AZD8233 low dose for subcutaneous injection.

Group Type EXPERIMENTAL

Part B:AZD8233

Intervention Type DRUG

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

Part C: Placebo

Placebo solution for subcutaneous injection.

Group Type PLACEBO_COMPARATOR

Part C: Placebo

Intervention Type DRUG

Placebo solution

Part C: AZD8233 medium dose

AZD8233 medium dose for subcutaneous injection.

Group Type EXPERIMENTAL

Part C: AZD8233

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Part A:Placebo

Placebo solution

Intervention Type DRUG

Part A:AZD8233

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

Intervention Type DRUG

Part B:Placebo

Placebo solution

Intervention Type DRUG

Part B:AZD8233

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

Intervention Type DRUG

Part C: Placebo

Placebo solution

Intervention Type DRUG

Part C: AZD8233

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

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
Minimum Eligible Age

20 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Chiyoda-ku, , Japan

Site Status

Research Site

Chūōku, , Japan

Site Status

Research Site

Chūōku, , Japan

Site Status

Research Site

Chūōku, , Japan

Site Status

Research Site

Osaka, , Japan

Site Status

Research Site

Shinjuku-ku, , Japan

Site Status

Research Site

Suita-shi, , Japan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Japan

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 38504437 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D7990C00006&amp;attachmentIdentifier=5acc6b71-a65b-42b0-a2b9-9fe64aa7f1c9&amp;fileName=d7990c00006-clinical-study-report-Combined_Redacted.pdf&amp;versionIdentifier=

CSRsynopsis

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D7990C00006&amp;attachmentIdentifier=eb305a4d-106e-464b-92d0-e179003c58ae&amp;fileName=d7990c00006-sap-part-Combined_redacted_2.pdf&amp;versionIdentifier=

SAP

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D7990C00006&amp;attachmentIdentifier=225151c3-a0fb-4f5b-8da4-d34867e59881&amp;fileName=d7990c00006-csp-v5_Redacted.pdf&amp;versionIdentifier=

CSPredacted

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

D7990C00006

Identifier Type: -

Identifier Source: org_study_id