Dyslipidemia
Conditions
Interventions
Experimental: AZD0780
Participants will receive oral AZD0780 once daily
Placebo Comparator: Placebo
Participants will receive oral placebo once daily
Sponsors
Ageishi Yuji
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Meets one of the following: 1. Participants with history of an ASCVD event: Participants 18 years of age or more at the time of signing the ICF with a history of MI or ischaemic stroke suspected to be due to atherosclerotic vascular disease 1 month or more prior to randomisation (presumed lacunar or cardioembolic strokes are not qualifying events), or revascularisation for symptomatic lower limb PAD any time prior to screening Additional risk factors based on the level of the LDL-C and timing of MI and stroke: o Participants with an LDL-C 75 mg/dL or more (1.9 mmol/L or more) need to have at least one of the other additional risk factors below. _ T2DM requiring ongoing medical therapy _ Age 65 years or more _ Previous above ankle amputation due to PAD _ Previous diagnosis of non-end stage CKD 2. Participants at increased risk of a first ASCVD event: Male participant 50 years of age or more, or female participant 55 years of age or more at the time of signing the ICF with LDL-C 100 mg/dL or more (2.6 mmol/L or more) and diagnostic evidence of at least one of the following disease categories (i, ii, or iii): i) Significant atherosclerotic artery disease ii) High-risk Type 1 or Type 2 diabetes mellitus with manifestation of at least one of the following end-organ disease: - Nephropathy - Persistent (2 readings or more) microalbuminuria (urine albumin/creatinine ration 30 mg/g or more) and/or persistent eGFR 1.4 - confirmed either in study during screening or randomisation, or from the medical record within the last 5 years iii) Documented atherosclerosis of less significance For ii) and iii), participants need to have at least one of the additional risk factors below: 1. CKD with eGFR xx mL/min/1.73 m2 or less 2. Current tobacco use 3. Age 65 or more 4. T2DM (if included on the less significant atherosclerosis criterion iii) 3 Participants should receive a background lipid lowering regimen anticipated to achieve at least a ~50% reduction in LDL-C. Except in cases of intolerance, the regimen should include a high intensity statin therapy or lower intensity statin therapy in combination with an oral agent with proven outcome benefit (eg, ezetimibe and/or bempedoic acid). Participants must achieve a stable background lipid-lowering therapy 28 days or more before screening.
Exclusion criteria
Exclusion criteria: - Any underlying known disease, or condition including homozygous familial hypercholesterolaemia, or LDL or plasma apheresis within 12 months prior to randomisation, that, in the opinion of the investigator, might interfere with the interpretation of the clinical study results. - Any revascularisation procedure planned within the next 3 months. - Available imaging assessment within the last 3 years showing either coronary calcium score of zero, or a coronary computed tomography angiography with no atherosclerosis. - Calculated eGFR 3 x ULN _ TBL > 2 x ULN (except for participants with Gilbert's syndrome where TBL 3 x ULN is acceptable provided direct bilirubin 5 x ULN _ Urine albumin/creatinine ratio 500 mg/g or more - Uncontrolled T2DM defined as HbA1c 9.5% or more at screening. - Inadequately treated hypothyroidism defined as TSH > 1.5 x ULN at screening or participants whose thyroid replacement therapy was initiated or modified within the last 3 months prior to screening. - Use of mipomersen or lomitapide (cholesterol-lowering medications) within 12 months of screening or planned use during the study. - Use of gemfibrozil within one week prior to the Screening Visit or planned use during the study. - Use of PCSK9 inhibitors: evolocumab/alirocumab within 12 weeks of the Screening Visit or planned use during the study, or inclisiran within 18 months of the Screening Visit or planned use during the study, or any other approved PCSK9 inhibitor use within 5 half lives prior to the Screening Visit or planned use during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first event of any component of MACE-PLUS | — |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Hungary, India, Italy, Japan, Malaysia, Mexico, New Zealand, Peru, Philippines, Poland, Republic of Korea, Rumania, Slovaki, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactYuji Ageishi
Astrazeneka K.K
Outcome results
None listed