Efficacy and Safety of EzetimiBe/Rosuvastatin in Diabetic Dislipidemia With Hypertriglyceridaemia

Study Overview
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Brief Summary
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To compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG > 200 mg/dL).

Detailed Description
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The purpose of this study is to compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG > 200 mg/dL).

Official Title
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A Multi-center, Randomized, Open-label, Active-controlled, Phase IV Clinical Trial to Evaluate the Efficacy and Safety of EzetimiBe/Rosuvastatin Diabetic Dislipidemia With Hypertriglyceridaemia

Conditions
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Endocrine System Diseases, Nutritional and Metabolic Diseases, Diabetes Mellitus, Type 2, Dyslipidemias

Intervention / Treatment
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* Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening (Visit 1) Inclusion Criteria Korean men and women aged 40 to 75 Patients who have been diagnosed with type 2 diabetes based on clinical judgment and satisfy diabetes diagnosis criteria Those who have no history of statin administration or who are receiving low- and moderate-intensity statin, and who have the following laboratory values on an empty stomach Low density lipoprotein-cholesterol (LDL-C) ≥ 100 mg/dL (direct measurement result) 200 mg/dL ≤ Triglyceride (TG) ≤ 499 mg/dL Those with less than 9% HbA1C Those who voluntarily agreed to participate in this clinical trial and signed a written ICF Randomization (Visit 2) Inclusion Criteria Persons with compliance 80% or more during Suvast tablet 5 mg Run-in period and with good TLC by investigator's judgment LDL-C ≥ 70 mg/dL (direct measurement result) at baseline (visit 2) Triglyceride (TG) ≥ 150 mg/dL at baseline (visit 2) Exclusion Criteria: Patients with hypersensitivity to the main ingredient (Ezetimibe or Rosuvastatin) and ingredients of IP Pregnant and lactating women, and women and men of childbearing potential who do not agree to conduct appropriate contraception during clinical trial Patients with Body Mass Index (BMI) < 15 kg/ m2 or > 35 kg/m2 Persons with the following medical history or surgical/interventional history Atherosclerotic disease occurring within 24 weeks at screening Myopathy including rhabdomyolysis Patients who have had a history of drug or alcohol abuse, or who have met drug or alcohol abuse criteria within 1 year at screening Major mental illness (depression, bipolar disorder, etc.) Malignant tumor within 5 years at screening Persons with the following comorbidities and laboratory abnormalities CK ≥ 2 X ULN Patients with severe hepatopathy (AST or ALT > 5 X ULN) Patients with unexplained persistent ALT elevation opinion or active liver disease TSH (Thyroid stimulating hormone) > 1.5 X ULN or those who do not maintain stable thyroid stimulating hormone level by investigator's judgment Uncontrolled hypertension (greater than sitBP 160/100 mmHg at screening) Renal disorder patients with severe renal failure (creatinine clearance (CLcr) Those who have the following history of drug administration within 3 months at screening Non-statin lipid modulators Foods or drugs that affect lipid control Systemic steroids Those who are expected to administer contraindication drugs during clinical trial, including screening Those who have persistent history of drinking within 1 week at clinical trial participation or who are unable to perform TLC due to continuous drinking during clinical trial Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorptioin Those who received other IPs or investigational medical devices within 30 days at screening Patients judged to be ineligible to participate in clinical trial by investigator's decision

Ages Eligible for Study
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Minimum Age: 40 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Subject administered with Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg) | Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)<br>* IP Test drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg) Control drug: Suvast tablet 10 mg (Rosuvastatin 10 mg)<br>* Other names: Suvast tablet 10 mg (Rosuvastatin 10 mg);|
| Active Comparator: Control group<br>Subject administered with Suvast tablet 10 mg (Rosuvastatin 10 mg) | Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)<br>* IP Test drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg) Control drug: Suvast tablet 10 mg (Rosuvastatin 10 mg)<br>* Other names: Suvast tablet 10 mg (Rosuvastatin 10 mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C change rate (percent, %) | To compare LDL-C change rate (percent, %) between test and control group | Baseline and 16 weeks | 
| Triglyceride (TG) change rate (percent, %) | To compare Triglyceride (TG) change rate (percent,%)between test and control group | Baseline and 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change rates (percent, %) of LDL-C and Triglyceride (TG) | To measure/compare Change rates (percent, %) of LDL-C and Triglyceride (TG) between test and control group | Baseline and 4 weeks | 
| Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C | To measure/compare Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C between test and control group | Baseline, 4 weeks, and 16 weeks | 
| Percent (%) of subjects with a 50% or more reduction in LDL-C level | To measure/compare Percent (%) of subjects with a 50% or more reduction in LDL-C level between test and control group | 4 weeks and 16 weeks | 
| Percent (%) of subjects with LDL-C below 70 mg/dL | To measure/compare Percent (%) of subjects with LDL-C below 70 mg/dL between test and control group | 4 weeks and 16 weeks | 
| Changes of lipoproteins (ApoA1, ApoB) | To measure/compare Changes of lipoproteins (ApoA1 (mg/dL), ApoB (mg/dL)) between test and control group | Baseline and 16 weeks | 
| Changes of lipoproteins (ApoB/ApoA1 ratio) | To measure/compare Changes of lipoproteins (ApoB/ApoA1 ratio) between test and control group | Baseline and 16 weeks | 
| Change of HOMA-IR | To measure/compare Change of HOMA-IR between test and control group | Baseline and 16 weeks | 
| Change of HbA1C (percentage, %) | To measure/compare Change of HbA1C (percentage, %) between test and control group | Baseline, 4 weeks, and 16 weeks | 
| Change (mg/dL) of Fasting Plasma Glucose (FPG) | To measure/compare Change (mg/dL) of Fasting Plasma Glucose (FPG) between test and control group | Baseline, 4 weeks, and 16 weeks | 
| Change (mg/dL) of hs-CRP | To measure/compare Change (mg/dL) of hs-CRP between test and control group | Baseline and 16 weeks | 
| Changes of plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) levels at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC | To measure/compare Changes of plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) levels at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC between test and control group | Baseline and 16 weeks | 
| On the graphs at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC, total Area Under the Curve (tAUC) of each plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) | To measure/compare On the graphs at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC, total Area Under the Curve (tAUC) of each plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) between test and control group | Baseline and 16 weeks | 
| Adverse event | To measure/compare Adverse event between test and control group | Baseline and 16 weeks | 
| Blood pressure | To measure/compare Blood pressure between test and control group | Baseline and 16 weeks | 
| Pulse | To measure/compare Pulse between test and control group | Baseline and 16 weeks | 
| Electrocardiogram (12-lead ECG) | Number(%) of participants with Clinically Significant or Normal Electrocardiogram (12-lead ECG) findings after study drug administration | -4 weeks and 16 weeks |