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

Phase 3

Completed

• Conditions: Primary Hypercholesterolemia
• Interventions: Drug: Rosuvastatin 5mg → HL140 5/10; Drug: HL140 5/10; Drug: HL140 10/10; Drug: HL140 20/10; Drug: Rosuvastatin 10mg → HL140 10/10; Drug: Rosuvastatin 20mg → HL140 20/10

• Registration Number: NCT03571087
• Lead Sponsor: Hanlim Pharm. Co., Ltd.

Brief Summary

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

Detailed Description

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

Study Timeline

• Study Start: 2014-09
• Primary Completion: 2015-08
• Study Completion: 2015-09
• Status Verified: 2018-06
• Study First Submitted: 2018-06-17
• Study First Submitted QC: 2018-06-17
• Study First Posted: 2018-06-27
• Last Update Submitted: 2018-08-12
• Last Update Posted: 2018-08-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 374

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rosuvastatin 5mg → HL140 5/10	Rosuvastatin 5mg → HL140 5/10	1. Treatment(W0\~W8): 6Tab./q.d. Rosuvastatin 5mg 2. Extension period(W9\~W20): 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg)
HL140 5/10	HL140 5/10	Treatment(W0\~W8), Extension(W9\~W20): : 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg)
HL140 10/10	HL140 10/10	Treatment(W0\~W8), Extension(W9\~W20): : 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg)
HL140 20/10	HL140 20/10	Treatment(W0\~W8), Extension(W9\~W20): : 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg)
Rosuvastatin 10mg → HL140 10/10	Rosuvastatin 10mg → HL140 10/10	1. Treatment(W0\~W8): 6Tab./q.d. Rosuvastatin 10mg 2. Extension period(W9\~W20): 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg)
Rosuvastatin 20mg → HL140 20/10	Rosuvastatin 20mg → HL140 20/10	1. Treatment(W0\~W8): 6Tab./q.d. Rosuvastatin 20mg 2. Extension period(W9\~W20): 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg)

Primary Outcome Measures

Name	Time	Method
Percentage change in LDL-Cholesterol from baseline	Week 8	Percentage change(%) in LDL-Cholesterol from baseline at week 8

Secondary Outcome Measures

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