A Trial to Learn Which of 4 Different Doses of AZD0780 is Safest and Best Helps Treat People With Dyslipidemia

Study Overview
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Brief Summary
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The primary purpose of this study is to measure the effect of different daily doses of AZD0780 on Low-Density Lipoprotein (LDL-C) levels compared with placebo in participants with dyslipidemia. The effect of AZD0780 versus placebo on other lipid parameters and inflammatory markers is also investigated. The concentration of AZD0780 in blood at specific timepoints is measured, and the safety and tolerability of AZD0780 will be evaluated. There is a follow-up after end of treatment, but expanded access is not available. The primary hypothesis is that at least one of the investigated doses of AZD0780 is superior to placebo in lowering LDL-C level, in percent change from baseline up to week 12.

Official Title
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A Phase IIb, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AZD0780 in Participants With Dyslipidemia

Conditions
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Dyslipidemia

Intervention / Treatment
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* Drug: AZD0780
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females of non-childbearing potential 18 to 75 years of age, inclusive, at the time of signing the informed consent. Participants with a fasting low-density lipoprotein cholesterol (LDL-C) higher than or equal to 70 mg/dL (1.8 mmol/L) and lower than or equal to 190 mg/dL (4.9 mmol/L) at screening. Participants with fasting triglycerides lower than 400 mg/dL (lower than 4.52 mmol/L) at screening. Should be receiving moderate or high-intensity statin therapy for more than or equal to 2 months prior to screening. There should be no planned medication or dose change during study participation. Body mass index between 19.0 and 40.0 kg/m^2. Exclusion Criteria: 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 hematological, renal, metabolic, gastrointestinal, respiratory, 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 hemoglobin A1c (HbA1c) greater than 10 percent at screening. Acute ischemic cardiovascular event in the last 12 months. Heart failure with New York Heart Association (NYHA) Class III-IV. 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, e.g., lung, liver, heart, bone marrow, renal. LDL or plasma apheresis within 12 months prior to randomization. Uncontrolled hypertension. Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized with equal distribution across 5 parallel treatment arms to either placebo or one of four AZD0780 doses.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>AZD0780, Dose 1 | Drug: AZD0780<br>* 3 tablets once daily, orally, for 12 weeks<br>|
| Experimental: Arm B<br>AZD0780, Dose 2 | Drug: AZD0780<br>* 3 tablets once daily, orally, for 12 weeks<br>|
| Experimental: Arm C<br>AZD0780, Dose 3 | Drug: AZD0780<br>* 3 tablets once daily, orally, for 12 weeks<br>|
| Experimental: Arm D<br>AZD0780, Dose 4 | Drug: AZD0780<br>* 3 tablets once daily, orally, for 12 weeks<br>|
| Placebo Comparator: Arm E<br>Placebo, matched for appearance | Drug: Placebo<br>* 3 tablets once daily, orally, for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) Level from Baseline to Week 12 | Blood samples will be collected and LDL-C level for baseline to week 12 assessed to evaluate the percent change. | From first day of treatment up to week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline of Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12, Where Missing Values are Imputed Using a Multiple Imputation Strategy | Blood samples will be collected and LDL-C level for baseline up to week 12 assessed to evaluate the percent change for the time period. Imputation of missing values will performed. | From first day of treatment up to week 12. | 
| AZD0780 Plasma Concentrations Summarized by Sampling Timepoint | Blood samples will be collected and the concentration of AZD0780 in plasma at specific timepoints used to assess the pharmacokinetics of AZD0780. | From zero at baseline up to week 12. | 
| Percent Change from Baseline at Week 12 in Other Lipid Parameters and Inflammatory Markers | Blood samples drawn at specific timepoints throughout the study will be assessed to investigate the percent change compared to placebo from baseline at week 12 in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Triglycerides, Non-High-Density Lipoprotein Cholesterol (non-HDL-C), Very Low-Density Lipoprotein Cholesterol (VLDL-C), Apolipoprotein A-1 (ApoA1), Apolipoprotein B-100 (ApoB), Lipoprotein (a) (Lp(a)), Remnant Cholesterol, and High-Sensitivity C-Reactive Protein (hsCRP). | From first day of treatment up to week 12. | 
| Safety and Tolerability of AZD0780 will be Assessed in Terms of Adverse Events (AEs), Vital Signs, Electrocardiogram (ECG), and Clinical Laboratory Evaluations. | Physical examinations, ECG, blood tests, and urine tests will be performed at specific timepoints. Any AE reported will be registered and assessed. The overall safety and tolerability will be assessed taking the combined results into consideration. | From first day of treatment up to week 14. Adverse events are reported from signed consent to week 14. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dyslipidemia,, Low-Density Lipoprotein Cholesterol