Efficacy and Safety of EzetimiBe/Rosuvastatin in Diabetic Dislipidemia With Hypertriglyceridaemia (REMBRANDT)

A Multi-center, Randomized, Open-label, Active-controlled, Phase IV Clinical Trial to Evaluate the Efficacy and Safety of EzetimiBe/Rosuvastatin Diabetic Dislipidemia With Hypertriglyceridaemia

To compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG > 200 mg/dL).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Endocrine System Diseases; Dyslipidemias; Nutritional and Metabolic Diseases
• Intervention / Treatment: Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg); Drug: Suvast tablet 10 mg (Rosuvastatin 10 mg)

Detailed Description

The purpose of this study is to compare and evaluate the effects of LDL-C and Triglyceride (TG) control on the first dose Ezetimibe/Statin (Rosuvastatin 5 mg/Ezetimibe 10 mg) combination therapy compared to the average dose Statin (Rosuvastatin 10 mg) monotherapy in patients with Type 2 diabetes with hypertriglyceridemia (TG > 200 mg/dL).

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan, Korea, Republic of
    • Korea University Ansan Hospital
  • Bucheon, Korea, Republic of
    • Soon Chun Hyang University Hospital Bucheon
  • Cheonan, Korea, Republic of
    • Soon Chun Hyang University Hospital Cheonan
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of
    • Yeongnam University Medical Center
  • Daejeon, Korea, Republic of
    • Eulji University Hospital
  • Gangdong, Korea, Republic of
    • Kyung Hee University Hosipital at Gangdong
  • Goyang-si, Korea, Republic of
    • Inje University Ilsan Paik Hospital
  • Guri-si, Korea, Republic of
    • Hanyang University Guri Hospital
  • Gwangju, Korea, Republic of
    • Chosun university hospital
  • Hwaseong-si, Korea, Republic of
    • Hallym University Medical Center-Dongtan
  • Inchon, Korea, Republic of
    • Inha University Hospital
  • Pusan, Korea, Republic of
    • Pusan National University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Yeouido St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St.Mary
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Gangnam Severance Hospital
  • Suwon, Korea, Republic of
    • Ajou University Hospital
  • Suwon, Korea, Republic of
    • The Catholic University of Korea, St. Vincent's Hospital
  • Sŏngnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Sŏngnam, Korea, Republic of
    • Gachon University, Donginchoen Gil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Screening (Visit 1) Inclusion Criteria

1. Korean men and women aged 40 to 75
2. Patients who have been diagnosed with type 2 diabetes based on clinical judgment and satisfy diabetes diagnosis criteria

3. Who have the following laboratory values on an empty stomach

   • Patients with no prior statin therapy

     • Low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL (measured directly or calculated; calculated LDL-C is applicable only when triglyceride levels are < 400 mg/dL)
     • 200 mg/dL ≤ Triglyceride (TG) ≤ 499 mg/dL

   • Patients currently receiving low- or moderate-intensity statin therapy

     • Low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL (measured directly or calculated; calculated LDL-C is applicable only when triglyceride levels are < 400 mg/dL)

   • 200 mg/dL ≤ Triglyceride (TG) ≤ 499 mg/dL
4. Those with less than 9% HbA1C
5. Those who voluntarily agreed to participate in this clinical trial and signed a written ICF

Randomization (Visit 2) Inclusion Criteria

1) Persons with compliance 80% or more during Suvast tablet 5 mg Run-in period and with good TLC by investigator's judgment

Exclusion Criteria:

1. Patients with hypersensitivity to the main ingredient (Ezetimibe or Rosuvastatin) and ingredients of IP
2. Pregnant and lactating women, and women and men of childbearing potential who do not agree to conduct appropriate contraception during clinical trial
3. Patients with Body Mass Index (BMI) < 15 kg/ m2 or > 35 kg/m2

4. Persons with the following medical history or surgical/interventional history

   • Atherosclerotic disease occurring within 24 weeks at screening
   • Myopathy including rhabdomyolysis
   • Patients who have had a history of drug or alcohol abuse, or who have met drug or alcohol abuse criteria within 1 year at screening
   • Major mental illness (depression, bipolar disorder, etc.)
   • Malignant tumor within 5 years at screening

5. Persons with the following comorbidities and laboratory abnormalities

   • CK ≥ 2 X ULN
   • Patients with severe hepatopathy (AST or ALT > 5 X ULN)
   • Patients with unexplained persistent ALT elevation opinion or active liver disease
   • TSH (Thyroid stimulating hormone) > 1.5 X ULN or those who do not maintain stable thyroid stimulating hormone level by investigator's judgment
   • Uncontrolled hypertension (greater than sitBP 160/100 mmHg at screening)
   • Renal disorder patients with severe renal failure (creatinine clearance (CLcr)<30 mL/min

6. Those who have the following history of drug administration within 3 months at screening

   • Non-statin lipid modulators
   • Foods or drugs that affect lipid control
   • Systemic steroids
7. Those who are expected to administer contraindication drugs during clinical trial, including screening
8. Those who have persistent history of drinking within 1 week at clinical trial participation or who are unable to perform TLC due to continuous drinking during clinical trial
9. Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorptioin
10. Those who received other IPs or investigational medical devices within 30 days at screening
11. Patients judged to be ineligible to participate in clinical trial by investigator's decision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group; Subject administered with Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)	Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg); Test drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)
Active Comparator: Control group; Subject administered with Suvast tablet 10 mg (Rosuvastatin 10 mg)	Drug: Suvast tablet 10 mg (Rosuvastatin 10 mg); - Control drug: Suvast tablet 10 mg (Rosuvastatin 10 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-C change rate (percent, %)	To compare LDL-C change rate (percent, %) between test and control group	Baseline and 16 weeks
Triglyceride (TG) change rate (percent, %)	To compare Triglyceride (TG) change rate (percent,%)between test and control group	Baseline and 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change rates (percent, %) of LDL-C and Triglyceride (TG)	To measure/compare Change rates (percent, %) of LDL-C and Triglyceride (TG) between test and control group	Baseline and 4 weeks
Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C	To measure/compare Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C between test and control group	Baseline, 4 weeks, and 16 weeks
Percent (%) of subjects with a 50% or more reduction in LDL-C level	To measure/compare Percent (%) of subjects with a 50% or more reduction in LDL-C level between test and control group	4 weeks and 16 weeks
Percent (%) of subjects with LDL-C below 70 mg/dL	To measure/compare Percent (%) of subjects with LDL-C below 70 mg/dL between test and control group	4 weeks and 16 weeks
Changes of lipoproteins (ApoA1, ApoB)	To measure/compare Changes of lipoproteins (ApoA1 (mg/dL), ApoB (mg/dL)) between test and control group	Baseline and 16 weeks
Changes of lipoproteins (ApoB/ApoA1 ratio)	To measure/compare Changes of lipoproteins (ApoB/ApoA1 ratio) between test and control group	Baseline and 16 weeks
Change of HOMA-IR	To measure/compare Change of HOMA-IR between test and control group	Baseline and 16 weeks
Change of HbA1C (percentage, %)	To measure/compare Change of HbA1C (percentage, %) between test and control group	Baseline, 4 weeks, and 16 weeks
Change (mg/dL) of Fasting Plasma Glucose (FPG)	To measure/compare Change (mg/dL) of Fasting Plasma Glucose (FPG) between test and control group	Baseline, 4 weeks, and 16 weeks
Change (mg/dL) of hs-CRP	To measure/compare Change (mg/dL) of hs-CRP between test and control group	Baseline and 16 weeks
Changes of plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) levels at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC	To measure/compare Changes of plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) levels at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC between test and control group	Baseline and 16 weeks
On the graphs at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC, total Area Under the Curve (tAUC) of each plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL)	To measure/compare On the graphs at 30-minute, 1-, 2-, 3-, 4-, 5-, and 6-hour before and after FMC in subjects who perform FMC, total Area Under the Curve (tAUC) of each plasma triglyceride (mg/dL), ApoB100 (mg/dL), and ApoB48 (mg/dL) between test and control group	Baseline and 16 weeks
Adverse event	To measure/compare Adverse event between test and control group	Baseline and 16 weeks
Blood pressure	To measure/compare Blood pressure between test and control group	Baseline and 16 weeks
Pulse	To measure/compare Pulse between test and control group	Baseline and 16 weeks
Electrocardiogram (12-lead ECG)	Number(%) of participants with Clinically Significant or Normal Electrocardiogram (12-lead ECG) findings after study drug administration	-4 weeks and 16 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Gangnam Severance Hospital
• Investigators: Principal Investigator: Kyong Soo Park, Dr., Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Actual): May 28, 2021
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Diabetes Mellitus; Hyperlipidemias; Lipid Metabolism Disorders; Diabetes Mellitus, Type 2; Dyslipidemias; Metabolic Diseases; Hypertriglyceridemia; Endocrine System Diseases; 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: REMBRANDT

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
• product manufactured in and exported from the U.S.: No