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

• Sponsor: Seoul National University Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04700436
• Collaborator: Gangnam Severance Hospital (Other)
• Enrollment: 240
• Locations: 28
• Arms: 2
• Anticipated Duration (Months): 22.8
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Endocrine System Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Dyslipidemias	Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg)	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jan 3, 2020
• Anticipated Primary Completion Date: May 28, 2021
• Anticipated Study Completion Date: Nov 26, 2021

Arms and Interventions

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); IP Test drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg) Control drug: Suvast tablet 10 mg (Rosuvastatin 10 mg); Other Names: Suvast tablet 10 mg (Rosuvastatin 10 mg)
Active Comparator: Control group Subject administered with Suvast tablet 10 mg (Rosuvastatin 10 mg)	Drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg); IP Test drug: Rosuzet tablet 10/5 mg (Ezetimibe 10 mg/Rosuvastatin 5 mg) Control drug: Suvast tablet 10 mg (Rosuvastatin 10 mg); Other Names: Suvast tablet 10 mg (Rosuvastatin 10 mg)

Outcome Measures

Primary Outcome Measures

1. LDL-C change rate (percent, %) [Baseline and 16 weeks]

   To compare LDL-C change rate (percent, %) between test and control group

2. Triglyceride (TG) change rate (percent, %) [Baseline and 16 weeks]

   To compare Triglyceride (TG) change rate (percent,%)between test and control group

Secondary Outcome Measures

1. Change rates (percent, %) of LDL-C and Triglyceride (TG) [Baseline and 4 weeks]

   To measure/compare Change rates (percent, %) of LDL-C and Triglyceride (TG) between test and control group

2. Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C [Baseline, 4 weeks, and 16 weeks]

   To measure/compare Changes (mg/dL) of Total cholesterol (TC), Triglyceride (TG), HDL-C, and non-HDL-C between test and control group

3. Percent (%) of subjects with a 50% or more reduction in LDL-C level [4 weeks and 16 weeks]

   To measure/compare Percent (%) of subjects with a 50% or more reduction in LDL-C level between test and control group

4. Percent (%) of subjects with LDL-C below 70 mg/dL [4 weeks and 16 weeks]

   To measure/compare Percent (%) of subjects with LDL-C below 70 mg/dL between test and control group

5. Changes of lipoproteins (ApoA1, ApoB) [Baseline and 16 weeks]

   To measure/compare Changes of lipoproteins (ApoA1 (mg/dL), ApoB (mg/dL)) between test and control group

6. Changes of lipoproteins (ApoB/ApoA1 ratio) [Baseline and 16 weeks]

   To measure/compare Changes of lipoproteins (ApoB/ApoA1 ratio) between test and control group

7. Change of HOMA-IR [Baseline and 16 weeks]

   To measure/compare Change of HOMA-IR between test and control group

8. Change of HbA1C (percentage, %) [Baseline, 4 weeks, and 16 weeks]

   To measure/compare Change of HbA1C (percentage, %) between test and control group

9. Change (mg/dL) of Fasting Plasma Glucose (FPG) [Baseline, 4 weeks, and 16 weeks]

   To measure/compare Change (mg/dL) of Fasting Plasma Glucose (FPG) between test and control group

10. Change (mg/dL) of hs-CRP [Baseline and 16 weeks]

    To measure/compare Change (mg/dL) of hs-CRP between test and control group

11. 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 [Baseline and 16 weeks]

    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

12. 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) [Baseline and 16 weeks]

    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

13. Adverse event [Baseline and 16 weeks]

    To measure/compare Adverse event between test and control group

14. Blood pressure [Baseline and 16 weeks]

    To measure/compare Blood pressure between test and control group

15. Pulse [Baseline and 16 weeks]

    To measure/compare Pulse between test and control group

16. Electrocardiogram (12-lead ECG) [-4 weeks and 16 weeks]

    Number(%) of participants with Clinically Significant or Normal Electrocardiogram (12-lead ECG) findings after study drug administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Those who have no history of statin administration or who are receiving low- and moderate-intensity statin, and who have the following laboratory values on an empty stomach

• Low density lipoprotein-cholesterol (LDL-C) ≥ 100 mg/dL (direct measurement result)

• 200 mg/dL ≤ Triglyceride (TG) ≤ 499 mg/dL

1. Those with less than 9% HbA1C

2. 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

2. LDL-C ≥ 70 mg/dL (direct measurement result) at baseline (visit 2)

3. Triglyceride (TG) ≥ 150 mg/dL at baseline (visit 2)

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

1. 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)

1. 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

1. Those who are expected to administer contraindication drugs during clinical trial, including screening

2. 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

3. Patients with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorptioin

4. Those who received other IPs or investigational medical devices within 30 days at screening

5. Patients judged to be ineligible to participate in clinical trial by investigator's decision

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Korea University Ansan Hospital	Ansan		Korea, Republic of
2	Soon Chun Hyang University Hospital Bucheon	Bucheon		Korea, Republic of
3	The Catholic University of Korea, Bucheon St. Mary's Hospital	Bucheon		Korea, Republic of
4	Soon Chun Hyang University Hospital Cheonan	Cheonan		Korea, Republic of
5	Keimyung University Dongsan Medical Center	Daegu		Korea, Republic of
6	Yeongnam University Medical Center	Daegu		Korea, Republic of
7	Eulji University Hospital	Daejeon		Korea, Republic of
8	Kyung Hee University Hosipital at Gangdong	Gangdong		Korea, Republic of
9	Inje University Ilsan Paik Hospital	Goyang-si		Korea, Republic of
10	Myongji Hospital	Goyang-si		Korea, Republic of
11	Hanyang University Guri Hospital	Guri-si		Korea, Republic of
12	Chosun University Hospital	Gwangju		Korea, Republic of
13	Hallym University Medical Center-Dongtan	Hwaseong-si		Korea, Republic of
14	Inha University Hospital	Inchon		Korea, Republic of
15	Pusan National University Hospital	Pusan		Korea, Republic of
16	Korea University Anam Hospital	Seoul		Korea, Republic of
17	Korea University Guro Hospital	Seoul		Korea, Republic of
18	Kyung Hee University Hospital	Seoul		Korea, Republic of
19	Samsung Medical Center	Seoul		Korea, Republic of
20	Seoul National University Hospital	Seoul		Korea, Republic of
21	The Catholic University of Korea, Seoul St.Mary	Seoul		Korea, Republic of
22	The Catholic University of Korea, Yeouido St. Mary's Hospital	Seoul		Korea, Republic of
23	Yonsei University Health System, Gangnam Severance Hospital	Seoul		Korea, Republic of
24	Yonsei University Health System, Severance Hospital	Seoul		Korea, Republic of
25	Ajou University Hospital	Suwon		Korea, Republic of
26	The Catholic University of Korea, St. Vincent's Hospital	Suwon		Korea, Republic of
27	Gachon University, Donginchoen Gil Hospital	Sŏngnam		Korea, Republic of
28	Seoul National University Bundang Hospital	Sŏngnam		Korea, Republic of

Sponsors and Collaborators

• Seoul National University Hospital
• Gangnam Severance Hospital

Investigators

• Principal Investigator: Kyong Soo Park, Dr., Principal Investigator

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kyong Soo Park, Principal Investigator, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT04700436
• Other Study ID Numbers: REMBRANDT
• First Posted: Jan 7, 2021
• Last Update Posted: Jan 7, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Dyslipidemias; Metabolic Diseases; Hypertriglyceridemia; Endocrine System Diseases; Rosuvastatin Calcium; Ezetimibe

Study Results

No Results Posted as of Jan 7, 2021