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

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

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

Study Overview

• Status: Completed
• Conditions: Primary Hypercholesterolemia
• Intervention / Treatment: 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

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 Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HL140 5/10; Treatment(W0~W8), Extension(W9~W20): : 6Tab./q.d. HL140 5/10(Rosuvastatin5mg/Ezetimibe10mg)	Drug: HL140 5/10; 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
EXPERIMENTAL: HL140 10/10; Treatment(W0~W8), Extension(W9~W20): : 6Tab./q.d. HL140 10/10(Rosuvastatin10mg/Ezetimibe10mg)	Drug: HL140 10/10; 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
EXPERIMENTAL: HL140 20/10; Treatment(W0~W8), Extension(W9~W20): : 6Tab./q.d. HL140 20/10(Rosuvastatin20mg/Ezetimibe10mg)	Drug: HL140 20/10; 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
EXPERIMENTAL: Rosuvastatin 5mg → HL140 5/10; 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; 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
EXPERIMENTAL: Rosuvastatin 10mg → HL140 10/10; 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; 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
EXPERIMENTAL: Rosuvastatin 20mg → HL140 20/10; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hanlim Pharm. Co., Ltd.
• Investigators: Study Chair: Kisik Kim, The Catholic University of Korea, Dagu St. Mary's Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: June 17, 2018
• First Submitted That Met QC Criteria: June 17, 2018
• First Posted (ACTUAL): June 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 12, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: HL_HL140_301