An Open-Label Study to Compare the Lipid Effects of Niacin ER and Simvastatin (NS) to Atorvastatin in Subjects With Hyperlipidemia or Mixed Dyslipidemia (SUPREME)

Study Overview
=================
Brief Summary
-----------------
To demonstrate that niacin ER and simvastatin (NS) tablets, when compared to atorvastatin (Lipitor®; Pfizer, Inc.), has superior high-density lipoprotein cholesterol (HDL-C) elevating effects at Week 12 in subjects with type II hyperlipidemia or mixed dyslipidemia who are currently off lipid-modifying therapy. This was a prospective, randomized, open-label, blinded endpoint (PROBE) study.

Official Title
-----------------
SUPREME: A 12-Week, Open-Label, Multicenter Study to Compare the Lipid Effects of Niacin ER and Simvastatin (NS) to Atorvastatin in Subjects With Hyperlipidemia or Mixed Dyslipidemia

Conditions
-----------------
Hyperlipidemia, Mixed Dyslipidemia

Intervention / Treatment
-----------------
* Drug: Niacin ER/Simvastatin Tablets
* Drug: atorvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must meet all of the following laboratory criteria: HDL-C <40 mg/dL for men and <50 mg/dL for women. LDL-C ≥130 mg/dL but <250 mg/dL. TG <350 mg/dL. Creatine phosphokinase (CPK) < 3 x upper limit of normal (ULN). Alanine aminotransferase (ALT); serum glutamic pyruvic transaminase [SGPT] and aspartate aminotransferase (AST); serum glutamic oxaloacetic transaminase [SGOT] < 1.3 x ULN. Subjects must also be reasonably compliant with the Therapeutic Lifestyle Changes (TLC) diet during the 4 to 5 week Screening Period prior to randomization (and be willing to comply for the duration of the study). Exclusion Criteria: Subjects who have a history of any important medical conditions or abnormalities (as specified in the protocol) that would preclude study inclusion

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Niacin ER/Simvastatin Tablets<br>* Up to 2000 mg/40 mg at bedtime<br>* Other names: Simcor;|
| Experimental: 2<br> | Drug: atorvastatin<br>* 40 mg at bedtime<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 12 | (Week 12 HDL-C minus baseline HDL-C) x 100/baseline HDL-C | From baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in HDL-C From Baseline to Week 8 | (Week 8 HDL-C minus baseline HDL-C) x 100/baseline HDL-C | From baseline to Week 8 | 
| Percent Change in Non-HDL-C From Baseline to Week 8 | (Week 8 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C | From baseline to Week 8 | 
| Percent Change in Non-HDL-C From Baseline to Week 12 | (Week 12 non-HDL-C minus baseline non-HDL-C) x 100/baseline non-HDL-C | From baseline to Week 12 | 
| Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 12 | (Week 12 LDL-C minus baseline LDL-C) x 100/baseline LDL-C | From baseline to Week 12 | 
| Percent Change in Triglycerides From Baseline to Week 12 | (Week 12 triglycerides minus baseline triglycerides) x 100/baseline triglycerides | From baseline to Week 12 | 
| Percent Change in LDL-C:HDL-C Ratio | (Week 12 LDL-C:HDL-C ratio minus baseline LDL-C:HDL-C ratio) x 100/baseline LDL-C:HDL-C ratio | From baseline to Week 12 | 
| Percent Change in Total Cholesterol From Baseline to Week 12 | (Week 12 total cholesterol minus baseline total cholesterol) x 100/baseline total cholesterol | From baseline to Week 12 | 
| Percent Change in Total Cholesterol:HDL-C Ratio | (Week 12 total cholesterol:HDL-C ratio minus baseline total cholesterol:HDL-C ratio) x 100/baseline total cholesterol:HDL-C ratio | From baseline to Week 12 | 
| Percent Change in Lipoprotein A From Baseline to Week 12 | (Week 12 lipoprotein A minus baseline lipoprotein A) x 100/baseline lipoprotein A | From baseline to Week 12 | 
| Percentage of Subjects Meeting With HDL-C >/= 40 mg/dL at Week 12 |  | 12 weeks | 
| Percentage of Subjects Meeting National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III Goal for LDL-C at Week 12 | For high-risk patients (coronary heart disease or equivalent), LDL-C < 100 mg/dL and non-HDL-C < 130 mg/dL; for moderate risk patients (having 2 risk factors), LDL-C < 130 mg/dL and non-HDL-C < 160 mg/dL; for low-risk patients (having 0 or 1 risk factor): LDL-C < 160 mg/dL and non-HDL-C < 190 mg/dL. | 12 weeks | 
| Percentage of Subjects With Triglycerides < 150 mg/dL at Week 12 |  | 12 weeks | 
| Percentage of Subjects With HDL-C >/= 40 mg/dL, LDL-C Meeting NCEP ATP III Goal, and Triglycerides < 150 mg/dL at Week 12 | NCEP ATP III goals for LDL-C are as follows: For high-risk patients, LDL-C < 100 mg/dL; for moderate risk patients, LDL-C < 130 mg/dL; for low-risk patients: LDL-C < 160 mg/dL. High-risk means coronary heart disease or risk equivalents; moderate risk means having at least 2 risk factors; low-risk means having no or 1 risk factor. | 12 weeks |