Study to Evaluate the Efficacy, Safety and Tolerability of AZD8233 Treatment in Participants With Dyslipidemia

Phase 1

• Conditions: Dyslipidemia, especially: evaluation of low-density lipoprotein cholesterol reduction at steady state at different doses of AZD8233 in order to select a therapeutic dose.; MedDRA version: 20.0Level: PTClassification code 10058108Term: DyslipidaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-000767-23-SK
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-14
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics:
Participants who have a fasting LDL-C = 70 mg/dL (1.8 mmol/L) but < 190 mg/dL (4.9 mmol/L) at screening (visit 2).
Have fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening (visit 2).
Should be receiving moderate- or high-intensity statin therapy (refer to Appendix H) as defined by the ACC/AHA guidelines on blood cholesterol management, or according to local guidelines.
Should be on stable medication for = 3 months prior to screening with no planned medication or dose change during study participation. The exception to this restriction is for fenofibrate; if the participant is receiving fenofibrate, the therapy must be stable for at least 6 weeks prior to randomization at a dose that is appropriate for the duration of the study in the judgement of the Investigator. Other fibrate therapy (and derivatives) are prohibited.
Weight: Body mass index between 19 and 40 kg/m2.
Sex: male or female.
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
(a)Male participants:
•Males must be surgically sterile or using, in conjunction with their female partner, a highly effective method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the final follow up visit to prevent pregnancy in a partner. Acceptable methods of contraception include birth control pills, injections, implants, or patches, IUDs, tubal ligation/occlusion, and vasectomy. A barrier method is not necessary if the female partner is sterilized. Male study participants must not donate or bank sperm during this same time period.
(b)Female participants:
•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. Women not of childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
?Women < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range.
?Women = 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 108
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 108

Exclusion Criteria

Medical Conditions
Estimated glomerular filtration rate < 40 mL/min/1.73m2 using the Chronic Kidney Disease-Epidemiology Collaboration equation (visit 1).
- History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- Any uncontrolled or serious disease, or any medical (eg, known major active infection or major haematological, renal, metabolic, gastrointestinal, or endocrine dysfunction) or surgical condition that, in the opinion of the Investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
- Poorly controlled type 2 diabetes mellitus, defined as HbA1c > 10% (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.
- Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds).
- High-risk of bleeding diathesis as judged by the Investigator.
- Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
- Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
- LDL or plasma apheresis within 12 months prior to randomization.
- Uncontrolled hypertension defined as sitting SBP > 160 mmHg or DBP > 90 mmHg (visit 1 or 3).
- Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm (visit 1 or 3).
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12 lead ECG as judged by the Investigator.
-QTcF > 470 ms; high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias.
- Mipomersen, or lomitapide within 12 months prior to randomization.
- Previous administration of AZD8233/AZD6615 or other PCSK9 inhibition treatment (approved or investigational).
- Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of last follow-up to first administration of the study intervention of this study or 5 half-lives from last dose to first administration of study intervention, whichever is the longest.
- Optional Genetic Sampling
Optional Genetic Sampling should be in line with following exclusion criteria: Previous allogeneic bone marrow transplant ; Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified