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

Diabetes Mellitus, Type 2 Clinical Trial

— REMBRANDT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04700436
• Other study ID #: REMBRANDT
• Status: Recruiting
• Phase: Phase 4
• Start date: January 3, 2020
• Est. completion date: November 26, 2021

Study information

• Verified date: January 2021
• Source: Seoul National University Hospital
• Contact: Kyong Soo Park, Dr.
• Phone: +82-2-2072-2946
• Email: kspark[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: November 26, 2021
• Est. primary completion date: May 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

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

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

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)

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Dyslipidemias
• Endocrine System Diseases
• Hypertriglyceridemia
• Metabolic Diseases
• Nutritional and Metabolic Diseases

Intervention

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)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Gangnam Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LDL-C change rate (percent, %)	To compare LDL-C change rate (percent, %) between test and control group	Baseline and 16 weeks
Primary	Triglyceride (TG) change rate (percent, %)	To compare Triglyceride (TG) change rate (percent,%)between test and control group	Baseline and 16 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes of lipoproteins (ApoB/ApoA1 ratio)	To measure/compare Changes of lipoproteins (ApoB/ApoA1 ratio) between test and control group	Baseline and 16 weeks
Secondary	Change of HOMA-IR	To measure/compare Change of HOMA-IR between test and control group	Baseline and 16 weeks
Secondary	Change of HbA1C (percentage, %)	To measure/compare Change of HbA1C (percentage, %) between test and control group	Baseline, 4 weeks, and 16 weeks
Secondary	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
Secondary	Change (mg/dL) of hs-CRP	To measure/compare Change (mg/dL) of hs-CRP between test and control group	Baseline and 16 weeks
Secondary	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
Secondary	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
Secondary	Adverse event	To measure/compare Adverse event between test and control group	Baseline and 16 weeks
Secondary	Blood pressure	To measure/compare Blood pressure between test and control group	Baseline and 16 weeks
Secondary	Pulse	To measure/compare Pulse between test and control group	Baseline and 16 weeks
Secondary	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