Efficacy and Safety of Combination of Rosuvastatin and Ezetimibe in Patients With Primary Hypercholesterolemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate efficacy and safety of HL140 in patients with primary hypercholesterolemia.

Detailed Description
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The purpose of this study is to demonstrate that the efficacy of combination drug of rosuvastatin/ezetimibe is superior to single rosuvastatin drug and to confirm the safety of combination drug of rosuvastatin/ezetimibe

Official Title
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A Multi Center, Randomized, Double-blind, Parallel, Factorial Design, Therapeutic Phase III Study to Evaluate the Efficacy and Safety of Combination of Rosuvastatin and Ezetimibe in Patients With Primary Hypercholesterolemia

Conditions
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Primary Hypercholesterolemia

Intervention / Treatment
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* Drug: HL140 5/10
* Drug: HL140 10/10
* Drug: HL140 20/10
* Drug: Rosuvastatin 5mg → HL140 5/10
* Drug: Rosuvastatin 10mg → HL140 10/10
* Drug: Rosuvastatin 20mg → HL140 20/10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged over 19 years Signed informed consent form At visit 1 and visit 2, LDL-Cholesterol ≤ 250mg/dL and Triglyceride ≤ 400mg/dL Exclusion Criteria: At visit 1, BMI ≥ 30kg/㎡ Has a history of myopathy or rhabdomyolysis cased by statin treatment, hereditary myopathy or family history and hypersensitivity to statin(HMG-CoA reductase inhibitor) and component of ezetimibe Has a Severe renal disorder(Ccr <30mL/min) or nephrotic syndrome Creatine Kinase > 5 x upper limit of normal ALT or AST > 3 x upper limit of normal Has a activity/chronic hepatic disease or HIV-positive Has a endocrine or metabolic diseases known to affect the serum phospholipid or protein Uncontrolled diabetes mellitus(HbA1c ≥9%) Hypothyroidism (TSH > 1.5 x upper limit of normal rate at the screening ) Uncontrolled hypertension (SBP ≥180mmHg or DBP ≥110mmHg) Has a acute arteriopathy(history of unstable angina, cardiac infarction, transient ischemic stroke, cerebrovascular disease, coronary artery bypass, coronary intervention within 12 weeks prior to screening) Severe heart failure (NYHA Class III or IV) Has a drug absorption disorder by gastrointestinal surgery or gastrointestinal disorder History of malignant tumor including myelogenous and lymphoma within 5 years (Participation is possible, if the tumor has not recurred for more than 5 years) Subject with genetic deficiency such as galactose intolerance, Lapp lactose deficiency or glucose-galactose malabsorption Female subjects of childbearing potential who disagree with the contraceptive methods(surgical sterilization, intrauterine device or condoms) Pregnant or breast-feeding Patients who have a drug or alcohol abuse or are being treated for psychological disorder Patients who were treated with other investigational drug within 12 weeks prior to screening Other patients who are inappropriate to participate in the study considered by the investigator or other study staffs

Ages Eligible for Study
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Minimum Age: 19 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HL140 5/10<br>Treatment(W0 W8), Extension(W9 W20): : 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg) | Drug: HL140 5/10<br>* 1) Treatment(W0 W8), Extension(W9 W20): 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg) : ●♤♡□△◇ ●: HL140 5/10mg, ♤: HL140 10/10mg placebo, ♡: HL140 20/10mg placebo, □: Crestor Tab.5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|
| Experimental: HL140 10/10<br>Treatment(W0 W8), Extension(W9 W20): : 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg) | Drug: HL140 10/10<br>* 1) Treatment(W0 W8), Extension(W9 W20): 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg) : ○♠♡□△◇ ○: HL140 5/10mg placebo, ♠: HL140 10/10mg, ♡: HL140 20/10mg placebo, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|
| Experimental: HL140 20/10<br>Treatment(W0 W8), Extension(W9 W20): : 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg) | Drug: HL140 20/10<br>* 1) Treatment(W0 W8), Extension(W9 W20): 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg) : ○♤♥□△◇ ○: HL140 5/10mg placebo, ♤: HL140 10/10mg placebo, ♥: HL140 20/10mg, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|
| Experimental: Rosuvastatin 5mg → HL140 5/10<br>Treatment(W0 W8): 6Tab./q.d. Rosuvastatin 5mg Extension period(W9 W20): 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg) | Drug: Rosuvastatin 5mg → HL140 5/10<br>* Treatment(W0 W8): 6Tab./q.d. Rosuvastatin 5mg : ○♤♡■△◇ ○: HL140 5/10mg placebo, ♤: HL140 10/10mg placebo,♡: HL140 20/10mg placebo, ■: Crestor Tab. 5mg, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo Extension period(W9 W20): 6Tab./q.d. HL1405/10(Rosuvastatin5mg/Ezetimibe10mg) : ●♤♡□△◇ HL140 5/10mg, ♤: HL140 10/10mg placebo, ♡: HL140 20/10mg placebo, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|
| Experimental: Rosuvastatin 10mg → HL140 10/10<br>Treatment(W0 W8): 6Tab./q.d. Rosuvastatin 10mg Extension period(W9 W20): 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg) | Drug: Rosuvastatin 10mg → HL140 10/10<br>* Treatment(W0 W8): 6Tab./q.d. Rosuvastatin 10mg : ○♤♡□▲◇ ○: HL140 5/10mg placebo, ♤: HL140 10/10mg placebo, ♡: HL140 20/10mg placebo, □: Crestor Tab. 5mg placebo, ▲: Crestor Tab. 10mg, ◇: Crestor Tab. 20mg placebo Extension period(W9 W20): 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg) : ○♠♡□△◇ HL140 5/10mg placebo, ♠: HL140 10/10mg, ♡: HL140 20/10mg placebo, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|
| Experimental: Rosuvastatin 20mg → HL140 20/10<br>Treatment(W0 W8): 6Tab./q.d. Rosuvastatin 20mg Extension period(W9 W20): 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg) | Drug: Rosuvastatin 20mg → HL140 20/10<br>* Treatment(W0 W8): 6Tab./q.d.Rosuvastatin 20mg : ○♤♡□△◆ ○: HL140 5/10mg placebo, ♤: HL140 10/10mg placebo, ♡: HL140 20/10mg placebo, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◆: Crestor Tab. 20mg Extension period(W9 W20): 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg) : ○♤♥□△◇ ○: HL140 5/10mg placebo, ♤: HL140 10/10mg placebo, ♥: HL140 20/10mg, □: Crestor Tab. 5mg placebo, △: Crestor Tab. 10mg placebo, ◇: Crestor Tab. 20mg placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in LDL-Cholesterol from baseline | Percentage change(%) in LDL-Cholesterol from baseline at week 8 | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in LDL-Cholesterol from baseline | Percentage change(%) in LDL-Cholesterol from baseline at week 4 | Week 4 | 
| Percentage change in TG from baseline | Percentage change(%) in TG from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage change in TC from baseline | Percentage change(%) in TC from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of change in non-HDL-Cholesterol | Percentage change(%) in non-HDL-Cholesterol from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of change in HDL-Cholesterol | Percentage change(%) in HDL-Cholesterol from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of change weeks in Apo A-I | Percentage change(%) in Apo A-I from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of change in Apo B | Percentage change(%) in Apo B from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of change in Lipoprotein(a) | Percentage change(%) in Lipoprotein(a) from baseline at week 4 and week 8 | Week 4, Week 8 | 
| The rate of change in hs-CRP | Percentage change(%) in hs-CRP from baseline at week 4 and week 8 | Week 4, Week 8 | 
| Percentage of patients reached treatment goals according to NCEP ATP III Guideline | Percentage(%) of patients reached treatment goal, by NCEP ATP III guideline, at week 4 and week 8 | Week 4, Week 8 |