Study to Compare the Effect of Vytorin (Simvastatin/Ezetimibe) 10/20mg Versus Atorvastatin 20mg on ApoB/ApoA1 Ratio in Subjects With Diabetes

A Single Center, Open Label, Randomized Study to Compare the Effect of Vytorin (Simvastatin/Ezetimibe) 10/20mg Versus Atorvastatin 20mg on ApoB/ApoA1 Ratio in Subjects With Diabetes

A single center, open label, randomized, clinical trial comparing ApoB/ApoA ratio of Vytorin 10/20mg vs atorvastatin 20mg treatment.

DM2 patients will be screened for inclusion criteria. Patients (n=66 in each arm) will be randomized to either Ezetimibe/simvastatin 10/20mg or atorvastatin 20mg after 4 week washout or TLC period. Primary and secondary endpoints will be assessed at week 12.

Primary endpoint:

1) change of ApoB/ApoA ratio at week 12.

Secondary endpoint:

1. Change of lipid parameters (TC, LDL-C, HDL-C, TG, apoB 48) at week 12.
2. Change of HbA1C at week 12.

3. Change of HOMA index at week 12

   - HOMA =[Fasting insulin (mIU/L) × Fasting glucose (mmol/L)] / 22.5

4. Change of hsCRP at week 12
5. Safety assessment

Hypotheses:

• Three months treatment of Vytorin 10/20mg will be superior to atorvastatin 20mg in ApoB/ApoA ratio.
• In DM patients, Ezetimibe/Simvastatin Combination will be well-tolerated.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus Without Insulin Treatment
• Intervention / Treatment: Drug: simvastatin/ezetimibe; Drug: atorvastatin 20mg

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hyun-Jae Kang; Phone Number: 82-2-2072-2279; Email: nowkang@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110744
    • Seoul National University Hospital
    • Principal Investigator: Hyun-Jae Kang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Type 2 DM
2. Hypercholesterolemia (baseline screening LDL-C > 100 mg/dL)
3. In case of medication, stable doses of oral hypoglycemic agents for at least three months
4. HbA1c <8.5%
5. Age: 20-80

Exclusion Criteria:

1. Chronic renal failure: creatinine > 3.0 mg/dL
2. Serious liver disease (> x3 LFT UNL)
3. Congestive heart failure
4. Stroke or MI/coronary intervention during the preceding 3 months.
5. CK > x 2.5 UNL
6. Unstable hypo/hyperthyroidism
7. Pregnant/lactating woman, or woman intending to become pregnant
8. Subject with any clinically significant condition or situation, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.

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: simvastatin/ezetimibe (vytorin) group; vytorin 10/20mg po once daily for 12weeks	Drug: simvastatin/ezetimibe; simvastatin/ezetimibe 10/20mg once daily for 12weeks
Active Comparator: atorvastatin group; atorvastatin 20mg po once daily for 12weeks	Drug: atorvastatin 20mg; atorvastatin 20mg once daily for 12weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of ApoB/ApoA1	change of ApoB/ApoA1	after 12 weeks' treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of lipid profile	change of total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglyceride, and APO B48	12weeks
change of HbA1c	change of HbA1c	12weeks
change of HOMA index	HOMA =[Fasting insulin (mIU/L) × Fasting glucose (mmol/L)] / 22.5	12weeks
change of hsCRP	change of hsCRP	12weeks
safety	CK elevation, Liver funtion test abnormality, and muscle realted adverse reactions and symptoms	during 12weeks of treatment

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Lee JH, Kang HJ, Kim HS, Sohn DW, Oh BH, Park YB. Effects of ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg on apolipoprotein B/apolipoprotein A1 in Korean patients with type 2 diabetes mellitus: results of a randomized controlled trial. Am J Cardiovasc Drugs. 2013 Oct;13(5):343-51. doi: 10.1007/s40256-013-0031-6.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): August 1, 2011

Study Registration Dates

• First Submitted: August 18, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Estimate): August 19, 2010
• Last Update Submitted That Met QC Criteria: August 18, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Simvastatin; Ezetimibe
• Other Study ID Numbers: H-1007-100-324