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

A Multi-center, Randomized, Double-blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Rosuvastatin and Ezetimibe and Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia

A Multi-center, Randomized, Double-blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Rosuvastatin and Ezetimibe and Rosuvastatin Monotherapy in Patients with Primary Hypercholesterolemia

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 382
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheongju-si, Korea, Republic of
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of
    • Yeungnam University Medical Center
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • Goyang-si, Korea, Republic of
    • Dongguk University Ilsan Hospital
  • Hwaseong-si, Korea, Republic of
    • Hallym University Dongtan Sacred Heart Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seongnam-si, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of
    • Chung-Ang University Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Soon Chun Hyang University Hospital Seoul
  • Seoul, Korea, Republic of
    • Hanyang University Hospital
  • Seoul, Korea, Republic of
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of
    • KyungHee University Hospital
  • Seoul, Korea, Republic of
    • Boramae Hospital
  • Suwon-si, Korea, Republic of
    • Ajou University Hospital
  • Wŏnju, Korea, Republic of
    • WonJu Severance Christian Hospital

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:

1. Adults aged 19 years or older
2. Patients with primary hypercholesterolemia
3. Patients who were informed about the purpose, method, effects, risks of this clinical study and have provided a written consent form signed by him/herself or by a representative
4. those who show an LDL-C level of 250 mg/dL or below and a TG level of less than 350 mg/dL at the run-in period (Week -1), and fall under the criterion of requiring the administration of antidyslipidemic drug of NCEP ATP III

Exclusion Criteria:

1. Patients with hypersensitivity to the investigational product or its ingredients
2. Those with an uncontrolled hypertension (SBP ≧ 180 mmHg or DBP ≧ 100 mmHg)
3. Those with a history of unstable angina, myocardial infarction, transient ischemic attack, cerebral vascular disease, coronary artery bypass or coronary intervention within 3 months of screening date
4. Those with a history of malignant tumor within 5 years
5. Those with a history of myopathy or rhabdomyolysis
6. Those who show clinically significant confirmed laboratory test results (1) Patients showing AST or ALT level of greater than 2 times the institutional upper limit of normal or those with active liver disease or chronic hepatitis (2) A serum creatinine level greater than 2 times the institutional upper limit of normal (3) HbA1c > 9% (4) Those with TSH level of greater than 1.5 times the institutional upper limit of normal (5) Those with CK level greater than 2 times the institutional upper limit of normal (However, except for an increase caused by a recent trauma, intramuscular injection or strenuous exercise)
7. Those who were given, within 4 weeks prior to the baseline (8 weeks in case of fibrate) or are expected to be given during the study period, a drug that can have an effect on the efficacy assessment of the clinical study (eg: antidyslipidemic drug (statins, ezetimibe, fibrates, BAS, nicotinic acid and derivative, etc.), systemic glucocorticosteroids, steatolytic enzyme inhibitor, cyclosporine, HIV proteinase inhibitor, macrolide class antibiotics, etc.)
8. Patients who were given estrogen within 3 months from the screening or those who are expected to be given an administration during the study period. (However, a patient who is under a hormone replacement therapy (HRT) will be allowed if no dose change is expected in the course of the clinical study.)
9. Those with a history of alcohol or drug abuse
10. Patients with a hereditary disorder of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
11. Pregnant or breast-feeding women
12. Women of childbearing potential or men who do not intend to use an adequate contraceptive measure during the study period and for 4 weeks after the end of the study(Adequate contraception: Administration and transplantation of a progestin-only contraceptive pill, intrauterine device, condom, spermicidal agent, etc.)
13. Patients who participated in another clinical study within 3 months from the screening date or have not had a washout period of at least 5 times the half-life of the active ingredient of the previously administered investigational product, whichever is longer
14. Those with drug malabsorption
15. Patients who has been judged by the investigator to be ineligible to participate in the clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RSV5mg + EZE 10mg; Rosuvastatin 5mg/Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe
Active Comparator: RSV5mg; Rosuvastatin 5mg	Drug: Rosuvastatin
Experimental: RSV10mg + EZE10mg; Rosuvastatin 10mg/ Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe
Active Comparator: RSV10mg; Rosuvastatin 10mg	Drug: Rosuvastatin
Experimental: RSV20mg + EZE10mg; Rosuvastatin 20mg/Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe
Active Comparator: RSV20mg; Rosuvastatin 20mg	Drug: Rosuvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline to 8 week in LDL-Cholesterol	baseline and 8 week

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline to 4 week in LDL-Cholesterol	baseline and 4 week
The change in the LDL-C level from the baseline to Week 4 and Week 8	baseline to 4 and 8 week
The change and percent change in the levels of TC, TG, HDL-C, non-HDL-C, apolipoprotein B, and hs-CRP from the baseline to Week 4 and Week 8	baseline to 4 and 8 week
The change and percent change in the ratios of LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I from the baseline to Week 4 and Week 8	baseline to 4 and 8 week
The ratio of the subjects who have reached the target LDL-C level according to the NCEP ATP(National Cholesterol Education Program Adult Treatment Panel) III Guideline at Week 4 and Week 8	baseline to 4 and 8 week

Collaborators and Investigators

• Sponsor: Shin Poong Pharmaceutical Co. Ltd.

Publications and helpful links

General Publications

• Kim W, Yoon YE, Shin SH, Bae JW, Hong BK, Hong SJ, Sung KC, Han SH, Kim W, Rhee MY, Kim SH, Lee SE, Hyon MS, Hwang GS, Son JW, Kim JY, Kim MK, Kim SW, Park JH, Shin JH, Park CG. Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia. Clin Ther. 2018 Jun;40(6):993-1013. doi: 10.1016/j.clinthera.2018.04.015. Epub 2018 May 30.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2014
• Primary Completion (Actual): November 19, 2015
• Study Completion (Actual): November 19, 2015

Study Registration Dates

• First Submitted: August 18, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (Actual): September 19, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: August 1, 2017

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; Ezetimibe
• Other Study ID Numbers: SP-RE-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No