A Study of AZD8233 in Participants With Dyslipidemia.

NCT04823611 | Completed Phase 1 Results FDA Drug

• 1 other identifier: D7990C00006
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 7

Brief 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. 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.

Conditions

Dyslipidemia

Keywords

AZD8233; Efficacy; PK; PD; Immunogenicity; Safety; Tolerability

Outcome Measures

Primary Outcomes (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

  Baseline to week 12

Secondary Outcomes (8)

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

  Measurement at baseline and week 12

• Part B: Change in PCSK9 in Plasma at Week 12

  Baseline to week 12

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

  Measurement at baseline and week 12

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

  Day 1 and Day 57

• Part A & Part C: Cmax of AZD8233

  Day 1 and Day 57

Study Arms (7)

Part A:Placebo

PLACEBO COMPARATOR

Placebo solution for subcutaneous injection.

Drug: Part A:Placebo

Part A:AZD8233

EXPERIMENTAL

AZD8233 for subcutaneous injection.

Drug: Part A:AZD8233

Part B:Placebo

PLACEBO COMPARATOR

Placebo solution for subcutaneous injection.

Drug: Part B:Placebo

Part B:AZD8233 medium dose

EXPERIMENTAL

AZD8233 medium dose for subcutaneous injection.

Drug: Part B:AZD8233

Part B:AZD8233 low dose

EXPERIMENTAL

AZD8233 low dose for subcutaneous injection.

Drug: Part B:AZD8233

Part C: Placebo

PLACEBO COMPARATOR

Placebo solution for subcutaneous injection.

Drug: Part C: Placebo

Part C: AZD8233 medium dose

EXPERIMENTAL

AZD8233 medium dose for subcutaneous injection.

Drug: Part C: AZD8233

Interventions

Part A:Placebo DRUG

Placebo solution

Part A:Placebo

Part A:AZD8233 DRUG

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

Part A:AZD8233

Part B:Placebo DRUG

Placebo solution

Part B:Placebo

Part B:AZD8233 DRUG

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

Part B:AZD8233 low dose; Part B:AZD8233 medium dose

Part C: Placebo DRUG

Placebo solution

Part C: Placebo

Part C: AZD8233 DRUG

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

Part C: AZD8233 medium dose

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (7)

Research Site

Chiyoda-ku, 1010041, Japan

Location

Research Site

Chūōku, 103-0027, Japan

Location

Research Site

Chūōku, 104-0031, Japan

Location

Research Site

Chūōku, 1040031, Japan

Location

Research Site

Osaka, 530-0001, Japan

Location

Research Site

Shinjuku-ku, 160-0008, Japan

Location

Research Site

Suita-shi, 565-0853, Japan

Location

Related Publications (1)

• 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.

  PMID: 38504437 DERIVED

Related Links

• CSRsynopsis
• SAP
• CSPredacted

MeSH Terms

Conditions

Dyslipidemias

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part A: Single blind Part B: Double blind Part C: Single blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: April 1, 2021
• Study Start: January 20, 2021
• Primary Completion: September 10, 2022
• Study Completion: September 10, 2022
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (7)