A Randomised, Parallel, Double-Blind, Placebo-Controlled Phase 2b Study to Assess the Safety, Tolerability and Efficacy of AZD8233 Treatment in Participants with Hyperlipidaemia (SOLANO)
- Conditions
- 1001331710003216High Blood Cholesterol levelsHyperlipidaemia10082206
- Registration Number
- NL-OMON52196
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 26
- 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 at screening
- Male or female of non-childbearing potential
- Signed and dated written informed consent prior to any mandatory study
specific procedures, sampling, and analyses
- 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Primary safety and tolerability will be evaluated in terms of AEs, vital<br /><br>signs, ECG, and clinical laboratory evaluations, including platelet count.<br /><br>- Primary efficacy will be evaluated in terms of the relative change in serum<br /><br>LDL-C from baseline to the end of Week 28.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Secondary efficacy will be evaluated in terms of the relative change in PCSK9<br /><br>from baseline to the end of Week 28.<br /><br>- Secondary PK: Model population PK parameters to be reported in a separate<br /><br>report<br /><br>- Secondary immunogenicity: Development of ADA (anti-drug antibodies) and titre<br /><br>(if participants are ADA positive) during treatment and follow-up</p><br>