Phase III Randomized Study Comparing Efficacy and Safety of Rosuvastatin/Fenofibrate vs. Pravastatin/Fenofibrate in Mixed Dyslipidemia Patients

The primary objective of this study is to demonstrate the **superiority** of the efficacy of a fixed-dose combination of **rosuvastatin** 20 mg and **fenofibrate** 160 mg compared to Pravafenix® in patients with mixed **dyslipidaemia** who are at high or very high risk for coronary heart disease and have not achieved target levels for Low-Density Lipoprotein Cholesterol (LDL-C ≥70 mg/dl for high-risk patients or ≥55 mg/dl for very high-risk patients). This is clinically relevant as achieving optimal LDL-C levels is crucial in reducing cardiovascular risk in these patients.

Secondary objectives include assessing the efficacy and describing the safety of the fixed-dose combination of rosuvastatin 20 mg and fenofibrate 160 mg over a 12-week treatment period. This evaluation is important to ensure that the treatment not only effectively manages lipid levels but also maintains a favorable safety profile.

The clinical trial involves participants diagnosed with **dyslipidaemia**, specifically those at high or very high risk of coronary heart disease. The study population includes both male and female subjects aged 18 years and older. Participants are required to have been treated with Pravafenix® for at least three months for mixed dyslipidaemia and must meet specific LDL-C thresholds, with ≥70 mg/dL for high-risk and ≥55 mg/dL for very high-risk individuals. The trial does not include a vulnerable population. Participants were selected based on their risk level as defined by the ESC/EAS guidelines (2019), which include criteria such as a calculated SCORE for 10-year risk of fatal cardiovascular disease, documented atherosclerotic cardiovascular disease, and diabetes mellitus with specific risk factors. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **phase III**, double-blind, randomized, two-arm, parallel study to evaluate the efficacy and safety of two fixed-dose combinations in patients with mixed **dyslipidaemia**. The trial will compare the administration of Rosuvastatin 20 mg and Fenofibrate 160 mg against Pravastatin 40 mg and Fenofibrate 160 mg (Pravafenix®) over a period of 12 weeks. The primary objective is to demonstrate the superiority of the Rosuvastatin and Fenofibrate combination in reducing Low-Density Lipoprotein Cholesterol (LDL-C) in high or very high coronary heart disease-risk patients who are not at goal for LDL-C levels. The trial will commence with a screening visit to confirm eligibility based on inclusion criteria such as age, prior treatment with Pravafenix®, and specific cardiovascular risk factors. Participants will be required to provide written informed consent and, if applicable, adhere to effective contraception measures.

The study will involve several key visits: an initial screening visit, baseline visit (V2), and subsequent follow-up visits culminating in the end-of-study visit at week 12 (V4). The primary endpoint is the mean percent change in LDL cholesterol from baseline to week 12. Secondary endpoints include changes in non-High-Density Lipoprotein cholesterol, High-Density Lipoprotein cholesterol, triglycerides, total cholesterol, and Apolipoprotein B, as well as the percentage of participants achieving target LDL-C levels. Safety assessments will include monitoring adverse events, serious adverse events, and specific adverse events of interest such as myopathy and rhabdomyolysis. The trial is expected to conclude by February 2026, with participant involvement lasting approximately 12 weeks. Conditions that may lead to early termination from the study include non-compliance with trial procedures or the occurrence of significant adverse events. The trial is not categorized as low intervention and is conducted under rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of two fixed-dose combination medications for the treatment of **mixed dyslipidaemia**. The experimental medication is a combination of **rosuvastatin** and **fenofibrate**, provided in a hard capsule form. Each capsule contains 20 mg of rosuvastatin and 160 mg of fenofibrate. The medication is administered orally, with a maximum daily dose of 20 mg of rosuvastatin and 160 mg of fenofibrate, and a total maximum dose of 1680 mg over the 12-week treatment period. The medication is classified under lipid-modifying agents, combinations, and is manufactured by Laboratoires SMB S.A. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen.

The comparator treatment in this study is Pravafenix, which is also provided in hard capsule form. Each capsule contains 40 mg of **pravastatin sodium** and 160 mg of fenofibrate. This medication is also administered orally, with a maximum daily dose of 40 mg of pravastatin sodium and 160 mg of fenofibrate, and a total maximum dose of 3360 mg over the 12-week treatment period. Pravafenix is similarly classified under lipid-modifying agents, combinations, and is produced by Laboratoires SMB S.A. The trial aims to compare the efficacy and safety of the experimental medication against Pravafenix in patients with mixed dyslipidaemia who are at high or very high risk of coronary heart disease.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints related to lipid profile changes in patients with mixed dyslipidaemia. The primary endpoint is the mean percent change from baseline to week 12 in **Low-Density Lipoprotein (LDL) cholesterol** levels. Secondary endpoints include mean percent changes from baseline to week 12 in non-High-Density Lipoprotein (non-HDL) cholesterol, HDL cholesterol, triglycerides, total cholesterol, and Apolipoprotein B (ApoB). Additionally, the percentage of participants achieving LDL-C levels below 55 mg/dL for very-high-risk patients or below 70 mg/dL for high-risk patients will be measured.

The trial will also monitor the incidence of adverse events, including serious adverse events and suspected unexpected serious adverse reactions, with a focus on adverse events of special interest such as myopathy and rhabdomyolysis. Absolute changes from baseline in laboratory data and the withdrawal rate will also be recorded. Efficacy parameters will be collected and analyzed at baseline (V2) and at week 12 (V4) using validated laboratory tests and patient-reported outcomes where applicable. The trial is designed as a phase III, double-blind, randomized, two-arm, parallel study comparing the efficacy and safety of two fixed-dose combinations over a 12-week period.