A Phase 2b Study to Assess the Safety, Efficacy and Tolerability of AZD8233 Treatment in Participants with Hyperlipidaemia

Phase 1

• Conditions: Hyperlipidaemia, evaluation of low-density lipoprotein cholesterol reduction and safety of AZD8233 vs. placebo; MedDRA version: 20.0Level: PTClassification code 10062060Term: HyperlipidaemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-005845-18-CZ
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-13
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 376

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 < 190 mg/dL
(4.9 mmol/L) at screening
-Participants who have fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at
screening
-Participants are receiving a stable dose (= 3 months) of maximally tolerated statin and/or ezetimibe therapy
-Male or female of non-childbearing potential
-Signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses
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 251
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

- eGFR < 40 mL/min/1.73m2 using the CKD-EPI
- 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 (according to the investigator’s judgment) if he/she participates in the clinical study
- Poorly controlled T2DM, defined as HbA1c > 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 < 50 or > 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 < lower limit of normal (LLN).
•Haemoglobin < 12 g/dL in males or < 11 g/dL in females
•Platelet count = LLN
•aPTT > 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

Study & Design

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