A Clinical Trial to Compare the Efficacy and Safety of a Combination Therapy of Ezetimibe and Rosuvastatin Versus Monotherapy of Rosuvastatin in Hypercholesterolemia Patients (I-ROSETTE Study) (I-ROSETTE)

A phase Ⅲ, multi-center, randomized, double-blinded, active comparator, factorial design clinical trial to compare the efficacy and safety of a combination therapy of ezetimibe and rosuvastatin versus monotherapy of rosuvastatin in hypercholesterolemia patients.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 19 ~ 79 years old
2. Patients who confirmed hypercholesterolemia.
3. Patients who requiring drug therapy according to NCEP ATP(National Cholesterol Education Program Adult Treatment Panel) III Guideline at Visit2.
4. Patients with Triglyceride< 400 at Visit 2.
5. Patients who have a wash-out period over 4 weeks for other drugs that can affect lipid profile.(Patients who have lipid regulators should have washout period over six weeks)
6. Patients who agreed to participate in the trial

Exclusion Criteria:

1. Patients who have a history of myopathy or rhabdomyolysis by statin treatment or hypersensitivity to statin HMG CoA(3-hydroxy-3-methylglutaryl-coenzyme) reductase inhibitors) or ezetimibe.
2. A heavy alcohol consumer. (alcohol > 25 units/week)
3. Patients with severe renal disease. (creatinine ≥ 2.0 mg/dL)
4. Patients with active liver disease and AST(aspartate transaminase) or ALT(alanine transaminase) > 2 times of upper limit of normal range.
5. Patients with CPK(creatine phosphokinase) > 2 x upper limit of normal range.
6. Patients who have a endocrine or metabolic diseases known to affect the serum phospholipid or lipoprotein.
7. Patients with HIV(human immunodeficiency virus positive.
8. Patients who have a acute arteriopathy.
9. Patients with uncontrolled hypertension.
10. Patients who have hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
11. Patients who have a drugs absorption disorder by gastrointestinal surgery or gastrointestinal disorder.
12. Patients with tumor.
13. Patients who have hormonal therapy.
14. Pregnancy or breastfeeding patients who don't agree to use adequate contraception.
15. Patients who are judged unsuitable to participate in this study by investigator.
16. Patients taking other clinical trial drugs within 30 days from the time of visit for screening.

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
Active Comparator: R5; Rosuvastatin 5mg	Drug: Rosuvastatin
Active Comparator: R10; Rosuvastatin 10mg	Drug: Rosuvastatin
Active Comparator: R20; Rosuvastatin 20mg	Drug: Rosuvastatin
Experimental: R5/E10; Rosuvastatin 5mg/Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe
Experimental: R10/E10; Rosuvastatin 10mg/Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe
Experimental: R20/E10; Rosuvastatin 20mg/Ezetimibe 10mg	Drug: Rosuvastatin; Drug: Ezetimibe

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 and 8 week in Total Cholesterol	baseline to 4 and 8 week
Percent change from baseline to 4 and 8 week in Triglyceride	baseline to 4 and 8 week
Percent change from baseline to 4 and 8 week in HDL-Cholesterol	baseline to 4 and 8 week
Percent change from baseline to 4 and 8 week in non-HDL-Cholesterol	baseline to 4 and 8 week
Percent change from baseline to 4 and 8 week in Apolipoprotein B	baseline to 4 and 8 week
Percent change from baseline to 4 and 8 week in Apolipoprotein A1	baseline to 4 and 8 week
Percent change from baseline to 4 week in LDL-Cholesterol	baseline to 4 week
Percent change from baseline to 4 and 8 week in hs-CRP(high-sensitivity C-reactive protein)	baseline to 4 and 8
The change of LDL-Cholesterol/HDL-Cholesterol ratio	baseline to 4 and 8 week
The change of Total Cholesterol/HDL-Cholesterol ratio	baseline to 4 and 8 week
The change of non-HDL-Cholesterol/HDL-Cholesterol ratio	baseline to 4 and 8 week
The change of Apolipoprotein B/Apolipoprotein A1 ratio	baseline to 4 and 8 week
The ratio of subjects who reach the goal of LDL-Cholesterol according to NCEP(National Cholesterol Education Program Adult Treatment Panel) III Guideline	baseline to 4 and 8 week

Collaborators and Investigators

• Sponsor: IlDong Pharmaceutical Co Ltd
• Investigators: Principal Investigator: Hyo-soo Kim, MD/PhD, Seoul National University Hospital

Publications and helpful links

General Publications

• Hong SJ, Jeong HS, Ahn JC, Cha DH, Won KH, Kim W, Cho SK, Kim SY, Yoo BS, Sung KC, Rha SW, Shin JH, Han KR, Chung WS, Hyon MS, Lee HC, Bae JH, Rhee MY, Kwan J, Jeon DW, Yoo KD, Kim HS. A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial. Clin Ther. 2018 Feb;40(2):226-241.e4. doi: 10.1016/j.clinthera.2017.12.018.

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 20, 2016
• First Posted (Estimate): April 25, 2016

Study Record Updates

• Last Update Posted (Actual): June 13, 2018
• Last Update Submitted That Met QC Criteria: June 11, 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; Ezetimibe
• Other Study ID Numbers: ID-ROEZ-302

Plan for Individual participant data (IPD)

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