Hyperlipidaemia, evaluation of low-density lipoprotein cholesterol reduction and safety of AZD8233 vs. placebo MedDRA version: 20.0 Level: PT Classification code 10062060 Term: Hyperlipidaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent -Participants who have a fasting LDL-C = 70 mg/dL (1.8 mmol/L) but =65 years) yes F.1.3.1 Number of subjects for this age range 125
Exclusion criteria
Exclusion criteria: - eGFR 10% - Acute ischaemic cardiovascular events including stroke within 30 days, or heart failure with New York Heart Association (NYHA) Class III to 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 or anti-platelet therapy other than low dose aspirin (=100mg/day). - Malignancy within the last 10 years - Recipient of any major organ transplant - LDL or plasma apheresis within 12 months prior to randomisation - Uncontrolled hypertension defined as average supine SBP > 160 mmHg or DBP > 90 mmHg - Heart rate after 10 minutes supine rest 100 bpm - Any laboratory values with the following deviations at the Screening Visit; test may be repeated at the discretion of the investigator if abnormal: • Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) • ALT > 1.5 × ULN • AST > 1.5 × ULN • TBL > ULN • ALP > 1.5 × ULN • WBC ULN or Prothrombin Time > ULN • UACR > 11 mg/mmol (100 mg/g) • UPCR > 300 mg/g -Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG -QTcF > 470 ms; high degree atrioventricular (AV)-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias -History of drug and/or alcohol abuse or a positive screen for drugs of abuse -use of warfarin, direct or indirect thrombin inhibitors or factor Xa inhibitors -Mipomersen, or lomitapide within 12 months prior to randomisation -Any fibrate therapy other than fenofibrate; if the participant is on fenofibrate therapy, the dose should be stable for at least 6 weeks prior to randomisation -Previous administration of AZD8233/AZD6615) or inclisiran (LEQVIO ® Novartis) -Use of evolocumab (REPATHA® Amgen) and alirocumab (PRALUENT® Regeneron) within 3 months of screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of AZD8233 as compared with placebo in participants with hyperlipidaemia receiving maximally tolerated statin and/or ezetimibe therapy as defined by the investigator • To assess the effect of AZD8233 versus placebo on serum LDL-C at the end of Week 28 compared with baseline, in participants with hyperlipidaemia, receiving maximally tolerated statin and/or ezetimibe therapy as defined by the investigator;Secondary Objective: -To assess the effect of AZD8233 versus placebo on plasma PCSK9 at the end of Week 28 compared with baseline, in participants with hyperlipidaemia, receiving maximally tolerated statin and/or ezetimibe therapy as defined by the investigator - To evaluate the PK of AZD8233 - To evaluate the immunogenicity of AZD8233;Primary end point(s): ? Safety and tolerability will be evaluated in terms of AEs, vital signs, ECG, and clinical laboratory evaluations, including platelet count ? The relative change in serum LDL-C from baseline to the end of Week 28;Timepoint(s) of evaluation of this end point: safety and tolerability: throughout the study efficacy: D197 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The relative change in PCSK9 from baseline to the end of Week 28 • Model population PK parameters to be reported in a separate report • Development of ADA and titre (if participants are ADA positive) during treatment and follow-up;Timepoint(s) of evaluation of this end point: PSCK9: D197 PK: D29, D85, D99, D141, D197 ADA: D1, D29, D57, D85, D113, D141, D169, D197, D281 | — |
Countries
Czechia, Czech Republic, Denmark, Hungary, Netherlands, Poland, Slovakia, Spain, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed