The purpose of this study is to evaluate the effectiveness of first-line treatment using Niaspan (an extended release version of niacin) and statins versus other drugs that lower lipid levels, in subjects with elevated fat levels in their blood (dyslipidemia). Statins are a class of medication that is often prescribed to patients who need to lower their cholesterol levels.

Condition	Treatment or Intervention	Phase
Dyslipidemia Coronary Heart Disease Atherosclerosis Stroke Diabetes	Drug: Niacin  Drug: Atorvastatin  Drug: Simvastatin  Drug: Ezetimibe  Drug: Rosuvastatin	Phase IV

Further Study Details: 

Expected Total Enrollment:  300

Name of Drugs: Niaspan (niacin extended-release tablets), Lipitor® (atorvastatin), Zocor® (simvastatin), Zetia™ (ezetimibe), and Crestor® (rosuvastatin)

Study Treatment: Four open-label parallel treatment groups for 12 weeks of observation

• Niaspan and atorvastatin combination treatment titrated to 2000 mg and 40 mg, respectively;
• combination treatment of simvastatin titrated to 40 mg and ezetimibe maintained at 10 mg;
• rosuvastatin monotherapy treatment titrated to 40 mg; and
• Niaspan and rosuvastatin combination treatment titrated to 1000 mg and 20 mg, respectively.

Objective: To evaluate the relative efficacy of first-line therapy using the combination of Niaspan and atorvastatin versus the combination of simvastatin and ezetimibe versus rosuvastatin monotherapy versus the combination of Niaspan and rosuvastatin in patients with dyslipidemia.

Population:

• Male or female patients 21 years of age or older
• Patients who are eligible for treatment based upon National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) recommendations at the end of the Qualification period;
• All patients must have mean triglycerides (TG) ≤ 300 mg/dL.

Design: A Phase IV, 12-week, randomized, multi-center, open-label, four-arm, parallel-group study evaluating the efficacy of Niaspan and statin therapy versus other lipid-modifying therapies preceded by a four-week washout of any previous lipid-lowering therapy.

Sample Size: Approximately 300 patients will be randomized equally to the four treatment groups.

Multi-center: Approximately 35 sites will participate.

Primary Endpoint: Mean percent change in LDL-C from Baseline to Week 12.

Secondary Endpoints: Mean percent change in high density lipoprotein cholesterol (HDL-C), TG, and non-high density lipoprotein cholesterol (non-HDL-C) from Baseline to Week 12.

Tertiary Endpoints: Lipid values including mean percent change in total cholesterol (TC) and the ratios of TC to HDL-C and LDL-C to HDL-C to Week 12. Safety variables such as serum transaminases, routine chemistry parameters, hematology, urinalysis, and adverse events will be evaluated as tertiary endpoints.

Adverse Events: Adverse events and flushing will be volunteered by patients and elicited by study staff.

Statistical Plan: All hypothesis tests will be two-sided and use a Type I error rate of 5%. The primary endpoint of mean percent change in LDL-C from Baseline to Week 12 will be evaluated using an ANOVA to assess differences across treatment groups. The secondary and tertiary endpoints will each be compared similarly across treatment groups in separate ANOVA models. If a statistically significant treatment group difference is found in an efficacy endpoint, relevant pairs of treatment groups will be compared using a procedure to control for Type I error in multiple comparisons. Adverse events will be tabulated by term and system organ class according to the MedDRA dictionary. Chi-square or Fisher’s Exact test will be used as appropriate to compare incidences between groups. Continuous-valued safety and efficacy variables will be summarized by treatment group and week using means (of observed and percent change values), the standard error of the mean, the median, the minimum, and the maximum. Discrete-valued safety and efficacy variables will be summarized by treatment group and week using frequencies and percents.

Ages Eligible for Study:  21 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

All of the following criteria must be answered “Yes”:

1. Patient is 21 years of age or older and willing to participate for the duration of the study;

2. Patient has read, signed, and agreed to the items listed in the informed consent form and HIPAA authorization form prior to the initiation of any study procedures and/or discontinuing any medications;

3. Patient is eligible for treatment following the drug washout period based upon the NCEP ATP III entry criteria and the LDL-C variability ≤ 15%;

4. Patient has mean triglyceride level (TG) ≤ 300 mg/dL;

5. Patient is willing to withdraw from any current anti-dyslipidemic medications or other prohibited medication for approximately 6 weeks prior to randomization (4 weeks prior to qualification visits) and for the duration of the study;

6. If the patient is female, the patient must not be pregnant or breast-feeding and not planning to become pregnant or to breast-feed for the duration of the study. Women of childbearing potential must commit to using a medically acceptable method of birth control such as oral contraception, intrauterine device (IUD), or a double-barrier method of contraception. Women using oral contraception must have done so for at least 3 months prior to randomization, and continue to do so for the duration of the study. To be considered not of childbearing potential, women must be post-menopausal for at least 2 years or surgically sterile.

Exclusion Criteria:

All the following criteria must be answered “No”:

1. Patient has an allergy, hypersensitivity, or intolerance to niacin, simvastatin, atorvastatin, ezetimibe, rosuvastatin or their derivatives;

2. Patient drinks more than 14 alcoholic drinks per week or has a previous history (within 12 months of screening) of substance abuse or dependency;

3. Patient has untreated or unsuccessfully treated psychiatric disease;

4. Patient has used an investigational study medication or participated in an investigational study within 30 days of obtaining qualification labs;

5. Patient has taken a prohibited medication within 4 weeks of obtaining qualification labs for the study (See section 8.0 - Concomitant Medications);

6. Patient has a history of any of the following:

• active gallbladder disease within the preceding 12 months (cholecystectomy is allowed);
• pancreatitis;
• liver disease (e.g., hepatitis B and/or C);
• persistent uncontrolled or untreated severe hypertension;
• Type I or Type II diabetes;
• persistent uncontrolled or untreated hypothyroidism;
• arterial bleeding;
• unstable angina;
• myocardial infarction, coronary artery bypass graft surgery, or angioplasty within the preceding 6 months;
• stroke, transient ischemic attack (TIA), or deep vein thrombosis (DVT) within the preceding 6 months;
• congestive heart failure NYHA class III or IV;
• active cancer within the last 5 years or a diagnosis of cancer within the last 5 years (excluding basal cell carcinoma);
• fibromyalgia, myopathy, rhabdomyolysis, unexplained muscle pain or weakness, and/or discontinuation of a statin because of myalgia; and/or
• life expectancy < 2 years.

7. Patient has any of the following abnormalities at any of the Screening or Qualification Visits:

• CPK elevation > 3xULN;
• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.3xULN;
• serum creatinine ≥ 1.5 mg/dL;
• creatinine clearance < 30 mL/min, as calculated using the Cockroft and Gault formula by the central laboratory;
• active gout symptoms and/or uric acid level > 1.3xULN;
• and/or active peptic ulcer disease;

8. Patient is planning to undergo major surgery within the next 6 months;

9. Patient has any health condition or laboratory abnormality that, in the opinion of the Principal Investigator, may be adversely affected by the procedures or medications in this study.

Roger Kohler, MS      (800) 722-4567 

Arizona
      Tatum Ridge Internal Medicine, Phoenix,  Arizona,  85032,  United States; Recruiting
California
      The Lindner Clinical Trial Center, Long Beach,  California,  90822,  United States; Recruiting
      Clinical Research Center of California, San Diego,  California,  92117,  United States; Recruiting
      Western Clinical Research, Inc., Torrance,  California,  90505,  United States; Recruiting
Connecticut
      Clinical Research Consultants, Inc., Trumbull,  Connecticut,  06611,  United States; Recruiting
Florida
      Meridian Research, St. Petersburg,  Florida,  33709,  United States; Recruiting
      University of Miami, Miami,  Florida,  33136,  United States; Recruiting
      Renstar Medical Research, Plantation,  Florida,  33324,  United States; Recruiting
      Miami Cardiology Group, Miami,  Florida,  33176,  United States; Recruiting
      Jacksonville Heart Center, PA, Jacksonville,  Florida,  32250,  United States; Recruiting
Illinois
      Fox Valley Cardiovascular Consultants, Aurora,  Illinois,  60506,  United States; Recruiting
Indiana
      Indiana University School of Medicine, Indianapolis,  Indiana,  46202,  United States; Recruiting
      Research Institute of Middle America River City Cardiology, Jeffersonville,  Indiana,  47130,  United States; Recruiting
Iowa
      Iowa Heart Center, PC, Des Moines,  Iowa,  50314,  United States; Recruiting
Kentucky
      L-MARC Research Center, Louisville,  Kentucky,  40213,  United States; Recruiting
Massachusetts
      Future Care Studies, Springfield,  Massachusetts,  01107,  United States; Recruiting
      Primary Care Cardiology Research, Inc., Ayer,  Massachusetts,  01432,  United States; Recruiting
Michigan
      Westside Family Medical Center, PC, Kalamazoo,  Michigan,  49009,  United States; Recruiting
Missouri
      Saint Luke's Lipid and Diabetes Research Center, Kansas City,  Missouri,  64111,  United States; Recruiting
New York
      Hudson Valley Clinical Research Center, Kingston,  New York,  12401,  United States; Recruiting
North Carolina
      Carolina Pharmaceutical Research, Statesville,  North Carolina,  28625,  United States; Recruiting
Ohio
      Riverside Methodist Hospital, Columbus,  Ohio,  43214,  United States; Recruiting
      The Lindner Clinical Trial Center, Cincinnati,  Ohio,  45219,  United States; Recruiting
Oklahoma
      COR Clinical Research, Oklahoma City,  Oklahoma,  73103,  United States; Recruiting
Pennsylvania
      Research Across America, Reading,  Pennsylvania,  19606,  United States; Recruiting
Rhode Island
      Omega Medical Research, Warwick,  Rhode Island,  02886,  United States; Recruiting
Texas
      Baylor College of Medicine / The Medicine / The Methodist Hospital, Houston,  Texas,  77030,  United States; Recruiting
      Cardiac Center of Texas, McKinney,  Texas,  75069,  United States; Recruiting
      Wilford Hall US Air Force Medical Center, Lackland AFB,  Texas,  78239-5300,  United States; Recruiting
      Tyler Cardiovascular Consultants, Tyler,  Texas,  75701,  United States; Recruiting
Virginia
      Hampton Roads Center for Clinical Research, Norfolk,  Virginia,  23532,  United States; Recruiting
      National Clinic Research, Richmond,  Virginia,  23294,  United States; Recruiting
Washington
      Northwest Lipid Research Clinic, Seattle,  Washington,  75069,  United States; Recruiting
Wisconsin
      Heart Care Associates, LLC, Milwaukee,  Wisconsin,  53233,  United States; Recruiting

Study ID Numbers:  001-09-03-CR; COMPELL
Record last reviewed:  October 2004
Last Updated:  October 29, 2004
Record first received:  March 10, 2004
ClinicalTrials.gov Identifier:  NCT00079638
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08