A Study to Evaluate Daily Pravastatin, Fenofibrate or Pravafen in the Treatment of Combined Hyperlipidemia

Condition(s) targeted: Combined Hyperlipidemia

Intervention: Pravastatin (Drug); Fenofibrate (Drug); Pravafen (Combination of Pravastatin and Fenofibrate) (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Sciele Pharma

This is a multi-center, double blind, prospective, longitudinal, randomized, 12-week study with a 52-week open-label follow-up to evaluate the safety and efficacy of daily administration of Pravastatin 40 mg or Fenofibrate 160 mg or Pravafen (the combination of both Pravastatin and Fenofibrate 40/160 mg) in the treatment of combined hyperlipidemia. There will be an open-label, 8-week, Selection Phase prior to randomization in which all patients will be stabilized on Pravastatin 40 mg/day. Following the Selection Phase, and if the patients meet all inclusion/exclusion criteria, they will be randomized to a three arm, double blind, 12-week Efficacy Phase during which they would receive either Pravastatin 40 mg or Fenofibrate 160 mg or Pravafen (the combination of Pravastatin and Fenofibrate 40/160 mg). The 12-week Efficacy Phase will be followed by an open-label, 52-week, Safety Phase in which all patients will receive Pravafen.

After the 8-week Selection Phase, patients that still meet the inclusion/exclusion criteria will be randomized on a 1: 1:2 ratio to Pravastatin 40 mg or Fenofibrate 160 mg or Pravafen (the combination of both Pravastatin and Fenofibrate 40/160 mg) for 12 weeks. After the completion of the 12-week double-blind phase of the study, all patients that haven't had changes in their well being, will be allowed to roll-over into the 52-week, open-label, follow-up portion of the study. During the 52 week, open label, Safety Phase of the study, all patients will receive Pravafen (the combination of Pravastatin and Fenofibrate 40/160 mg).

Patients will be evaluated at baseline and every three weeks thereafter throughout the initial 12-week Efficacy Phase of the study. Patients that roll-over into the 52-week, open-label, follow-up Safety Phase will be evaluated at 12, 24, 36 and 52 weeks.

Participation in the study can be up to 72 weeks.

Official title: A Multi-Center, Prospective, Longitudinal, Randomized, Double-Blind, Phase III Study to Evaluate the Efficacy and Safety of Daily Administration of Pravastatin 40 mg or Fenofibrate 160 mg or Pravafen (the Combination of Pravastatin and Fenofibrate 40/160 mg) for 12 Weeks Followed by a 52-Week Open-Label Safety Phase of the Pravafen Alone in the Treatment of Combined Hyperlipidemia.

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Primary endpoints will assess differences in change from baseline in non-HDL-C, for the patients receiving Pravafen versus the patients receiving Pravastatin or Fenofibrate at the end of the 12-week portion of the study.

Secondary outcome:

Secondary endpoints will assess differences in change from baseline in TC, TG, LDL-C, HDL-C and TC/HDL-C for the pts receiving the combo therapy vs the pts receiving Pravastatin or Fenofibrate

Differences in change from baseline in ALT, AST and CK as well as overall safety for the pts receiving the combo therapy vs the pts receiving Pravastatin or Fenofibrate at the end of the 12-week of the study

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

Patients meeting all the criteria listed below may be selected to enroll into the Selection Phase of the study:

1. Male or female patients from 18-75 years of age, inclusive at the time of dosing with a history of a combined hyperlipidemia.

2. High LDL cholesterol and TG levels as per the table hereunder:

Prior treatment LDL Cholesterol TG Naïve to treatment* > 130 mg/dL and ≥ 150 mg/dL and ≤ 400 mg/dL Lipid Lowering Monotherapy > 130 mg/dL and ≥ 150 mg/dL and ≤ 400 mg/dL Lipid Lowering Combination Therapy > 110 mg/dL and ≥ 150 mg/dL and ≤ 400 mg/dL

* A patient that has received NO lipid lowering therapy within 6 weeks prior to the Selection Visit, will be considered Naïve to treatment.

3. If the patient is female and of childbearing potential and sexually active, an acceptable birth control method must be used (abstinence, IUD, oral, transdermal, injectable or implantable contraceptives, at least 2 years post-menopausal, one year post hysterectomy, double barrier device and/or partner at least one year post vasectomy), a negative serum pregnancy test must be obtained at the Selection Visit (Visit 1) and a negative urine pregnancy test must be obtained prior to study drug administration at Baseline Visit (Visit 3).

4. Able to comply with all study procedures.

5. Patients that provide a written informed consent to participate in the study indicated by a personal signature and date on the patient consent form.

At the end of the Selection Phase, patients meeting all of the criteria listed below may be selected and randomized into the Efficacy Phase of the study:

1. Selected patients with LDL Cholesterol ≥ 100 mg/dl and/or TG ≥ 150 mg/dl and ≤ 400 mg/dl at Week-1 / Visit 2 after taking Pravastatin 40 mg/day from Visit 1.

2. Patients still meeting the selection criteria a, c, d and e as listed under section 4. 1.

3. Patients with a compliance ≥ 80% during the 8-week Pravastatin phase of the study.

Exclusion Criteria:

Patients will be excluded from the study if any one or more of the following apply:

1. Female of childbearing potential who is pregnant and/or lactating and/or sexually active but not using an acceptable method of contraception

2. History of allergy or contraindications to:

- fenofibrate or similar compounds

- HMG-CoA reductase inhibitors

3. History of uncontrolled or unstable;

- diabetes ((i. e., diabetic nephropathy etc.),

- hepatic impairment/insufficiency,

- renal impairment/insufficiency (i. e., nephritis, polycystic kidney disease, acute

or chronic renal failure, end-stage renal disease, GFR < 60 ml/min, etc.),

- neurological,

- gastrointestinal (ulcerative colitis, Barrett's, etc.),

- gallbladder disease (patients with prior cholecystectomy can be allowed to

participate),

- psychiatric disease,

- sleep apnea

- any other clinically significant medical or surgical history that could affect

the safety of the patient or hinder the evaluation of drug effect based on Investigator or Medical Monitor discretion

4. Acute liver disease or persistent elevations in liver function tests (2 times the upper normal limit or greater)

5. Levels of creatine phosphokinase (CK) 3 times the upper normal limit or greater

6. Change in diuretic or β-blocker treatment for hypertension within 30 days of enrollment into the selection phase (Visit 1)

7. Positive personal history of abuse of any of the following:

- Alcohol (as per the DSM-IV criteria) and/or

- Recreational drugs (as per the DSM-IV criteria)

8. Usage of any of the following medications (patients must have discontinued these medications for 5 or more half-lives or for 30 days, whichever is greater prior to study drug administration on Visit 3 / Day 0) :

- Corticosteroids

- Immunosuppressants

- Macrolide antibiotics

- Azole antifungal agents, or

9. Recent use of any investigational drug. These drugs must have been discontinued for either 5 or more half-lives or for 30 days whichever is greater prior to Visit 1

10. Hyperlipidemia type I-IIa-IV-V

11. LDL < 100 mg/dL

12. TG < 150 mg/dL or > 400 mg/dL

13. Uncontrolled primary hypothyroidism

14. History of an acute myocardial infarction, stroke within the last 6 month prior to Visit 1; unstable angina or clinically significant heart failure

15. Uncontrolled hypertension, as defined by SBP >160 mmHg or DBP >100 mmHg while on anti-hypertensive medication

16. Type 1 diabetes or type 2 diabetes mellitus requiring insulin, and diabetic patients with poor control (HbA1c level > 8. 5%), abnormal renal function (GFR < 60 ml/mn) or any renal disease likely to lead to renal dysfunctions)

17. Use of any of the prohibited medications as detailed in the concomitant medication section

18. Non adherence to the American Heart Association Step II diet introduced at Visit 1

19. Presence of any other condition or illness, which, in the opinion of the Principal Investigator, would interfere with the patient's participation in the study

-

Cochise Clinical Research, Sierra Vista, Arizona 85635, United States

Anasazi Internal Medicine, Phoenix, Arizona 85032, United States

Memorial Research Medical Clinic, Long Beach, California 90806, United States

Orange County Research Center, Tustin, California 92780, United States

Clinical Trials Research, Roseville, California 95661, United States

Mima Century Research Associates, Melbourne, Florida 32901, United States

Cardiology Research Associates, Ormand Beach, Florida 32174, United States

Jacksonville Center for Clinical Research, Jacksonville, Florida 32216, United States

Jacksonville Center for Clinical Research, Jacksonville, Florida 32205, United States

Drug Study Institute, Jupiter, Florida 33458, United States

Atlanta Vascular Research Foundation, 30084, Georgia 30084, United States

East-West Medical Research Institute, Honolulu, Hawaii 96814, United States

Research Institute of Middle America, Jeffersonville, Indiana 47130, United States

MediSphere Medical Research Center LLC, Evansville, Indiana 47714, United States

Welborn Clinic Research Center, Evansville, Indiana 47713, United States

Welborn Clinic Gateway, Newburgh, Indiana 47630, United States

Lemarc Research Center, Lousville, Kentucky 40213, United States

Bluegrass Clinical Research, Inc., Louisville, Kentucky 40291, United States

Androscoggin Cardiology Associates, Auburn, Maine 04210, United States

Health Trends Research, LLC, Baltimore, Maryland 21208, United States

MD Medical Research, Oxon Hill, Maryland 20745, United States

MODEL Clinical Research, Baltimore, Maryland 21204, United States

Clinical Research Center of Cape Cod, Inc, West Yarmouth, Massachusetts 02673, United States

Mercy Medical Group, Manchester, Missouri 63021, United States

Clinical Study Site, Florissant, Missouri 63031, United States

Comprehensive Clinical Research, Berlin, New Jersey 08009, United States

Capital Cardiology Associates, Troy, New York 12180, United States

Bronx Nephrology Hypertension, P.C., Bronx, New York 10467, United States

Piedmont Medical Research Associates, Winston-Salem, North Carolina 27103, United States

Metrolina Medical Research, Charlotte, North Carolina 28209, United States

Wake Research Associates, Raleigh, North Carolina 27612, United States

Sensenbrenner Primary Care LLC, Charlotte, North Carolina 28277, United States

Crescent Medical Research Associates, Salisbury, North Carolina 28144, United States

Triangle Medical Research Associates, Raleigh, North Carolina 27609, United States

Wells Institute for Health Awareness, Kettering, Ohio 45429, United States

Sterling Research Group, Cincinnati, Ohio 45219, United States

Ohio Clinical Research, LLC, Lyndhurst, Ohio 44124, United States

The Lindner Clinical Trial Center, Cincinnati, Ohio 45219, United States

Ohio Clinical Research, Hudson, Ohio 44236, United States

Lynn Institute of Norman, Norman, Oklahoma 73071, United States

Bluestem Cardiology, Bartlesville, Oklahoma 74006, United States

Willamette Valley Clinical Studies, Eugene, Oregon 97404, United States

Fleetwood Clinical Research, Fleetwood, Pennsylvania 19522, United States

Tipton Medical Center, Tipton, Pennsylvania 16684, United States

Philadelphia Clinical Research, LLC, Philadelphia, Pennsylvania 09114, United States

Southern Berks Family Medicine, Reading, Pennsylvania 19606, United States

Upstate Pharmaceutical Research, Simpsonville, South Carolina 29681, United States

Palmetto Medical Research Associates, Mt. Pleasant, South Carolina 29464, United States

Holston Medical Group, Kingsport, Tennessee 37660, United States

TriCities Medical Research Associates, Bristol, Tennessee 37620, United States

Texas Medical Research LLC, San Antonio, Texas 78238, United States

Clinical Trials Research, Austin, Texas 78705, United States

Hampton Roads Center for Clinical Research, Norfolk, Virginia 23502, United States

Clinical Research Associates of Tidewater, Norfolk, Virginia 23507, United States

National Clinical Research, Richmond, Virginia 23294, United States

Cedar Research LLC, Tacoma, Washington 98405, United States

Rainier Clinical Research Center Inc., Renton, Washington 98057, United States

Starting date: April 2007
Last updated: January 25, 2008