A Study to Evaluate Daily Pravastatin, Fenofibrate or Pravafen in the Treatment of Combined Hyperlipidemia
- Conditions
- Combined Hyperlipidemia
- Interventions
- Registration Number
- NCT00459745
- Lead Sponsor
- Shionogi
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 481
Patients meeting all the criteria listed below may be selected to enroll into the Selection Phase of the study:
-
Male or female patients from 18-75 years of age, inclusive at the time of dosing with a history of a combined hyperlipidemia.
-
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.
-
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).
-
Able to comply with all study procedures.
-
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:
- 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.
- Patients still meeting the selection criteria a, c, d and e as listed under section 4.1.
- Patients with a compliance ≥ 80% during the 8-week Pravastatin phase of the study.
Patients will be excluded from the study if any one or more of the following apply:
-
Female of childbearing potential who is pregnant and/or lactating and/or sexually active but not using an acceptable method of contraception
-
History of allergy or contraindications to:
- fenofibrate or similar compounds
- HMG-CoA reductase inhibitors
-
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
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Acute liver disease or persistent elevations in liver function tests (2 times the upper normal limit or greater)
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Levels of creatine phosphokinase (CK) 3 times the upper normal limit or greater
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Change in diuretic or β-blocker treatment for hypertension within 30 days of enrollment into the selection phase (Visit 1)
-
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)
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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
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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
-
Hyperlipidemia type I-IIa-IV-V
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LDL < 100 mg/dL
-
TG < 150 mg/dL or > 400 mg/dL
-
Uncontrolled primary hypothyroidism
-
History of an acute myocardial infarction, stroke within the last 6 month prior to Visit 1; unstable angina or clinically significant heart failure
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Uncontrolled hypertension, as defined by SBP >160 mmHg or DBP >100 mmHg while on anti-hypertensive medication
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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)
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Use of any of the prohibited medications as detailed in the concomitant medication section
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Non adherence to the American Heart Association Step II diet introduced at Visit 1
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pravafen (Parvastatin and Fenofibrate) Pravafen Combined Therapy of Pravastatin 40 mg and Fenofibrate 160 mg. Fenofibrate Fenofibrate Fenofibrate 160 mg Pravastatin Pravastatin Pravastatin 40 mg
- Primary Outcome Measures
Name Time Method 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. bBaseline to 12 weeks Change in HDL
- Secondary Outcome Measures
Name Time Method 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 Baseline to 12 weeks Changes in TC, TG, LDL-C, HDL-C and TC/HDL-C
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 Baseline to 12 weeks Changes in ALT, AST and CK and overall safety
Trial Locations
- Locations (55)
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Welborn Clinic Gateway
🇺🇸Newburgh, Indiana, United States
Memorial Research Medical Clinic
🇺🇸Long Beach, California, United States
Cochise Clinical Research
🇺🇸Sierra Vista, Arizona, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Drug Study Institute
🇺🇸Jupiter, Florida, United States
Clinical Trials Research
🇺🇸Austin, Texas, United States
Southern Berks Family Medicine
🇺🇸Reading, Pennsylvania, United States
Wells Institute for Health Awareness
🇺🇸Kettering, Ohio, United States
Texas Medical Research LLC
🇺🇸San Antonio, Texas, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Bluegrass Clinical Research, Inc.
🇺🇸Louisville, Kentucky, United States
Hampton Roads Center for Clinical Research
🇺🇸Norfolk, Virginia, United States
Research Institute of Middle America
🇺🇸Jeffersonville, Indiana, United States
Philadelphia Clinical Research, LLC
🇺🇸Philadelphia, Pennsylvania, United States
Ohio Clinical Research
🇺🇸Hudson, Ohio, United States
Upstate Pharmaceutical Research
🇺🇸Simpsonville, South Carolina, United States
Welborn Clinic Research Center
🇺🇸Evansville, Indiana, United States
Cardiology Research Associates
🇺🇸Ormond Beach, Florida, United States
Bluestem Cardiology
🇺🇸Bartlesville, Oklahoma, United States
Fleetwood Clinical Research
🇺🇸Fleetwood, Pennsylvania, United States
TriCities Medical Research Associates
🇺🇸Bristol, Tennessee, United States
National Clinical Research
🇺🇸Richmond, Virginia, United States
Ohio Clinical Research, LLC
🇺🇸Lyndhurst, Ohio, United States
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
Palmetto Medical Research Associates
🇺🇸Mount Pleasant, South Carolina, United States
Sterling Research Group
🇺🇸Cincinnati, Ohio, United States
The Lindner Clinical Trial Center
🇺🇸Cincinnati, Ohio, United States
Tipton Medical Center
🇺🇸Tipton, Pennsylvania, United States
Atlanta Vascular Research Foundation
🇺🇸Atlanta, Georgia, United States
Mima Century Research Associates
🇺🇸Melbourne, Florida, United States
MediSphere Medical Research Center LLC
🇺🇸Evansville, Indiana, United States
Androscoggin Cardiology Associates
🇺🇸Auburn, Maine, United States
MODEL Clinical Research
🇺🇸Baltimore, Maryland, United States
Lemarc Research Center
🇺🇸Louisville, Kentucky, United States
Health Trends Research, LLC
🇺🇸Baltimore, Maryland, United States
MD Medical Research
🇺🇸Oxon Hill, Maryland, United States
Clinical Research Center of Cape Cod, Inc
🇺🇸West Yarmouth, Massachusetts, United States
Clinical Study Site
🇺🇸Florissant, Missouri, United States
Sensenbrenner Primary Care LLC
🇺🇸Charlotte, North Carolina, United States
Mercy Medical Group
🇺🇸Manchester, Missouri, United States
Bronx Nephrology Hypertension, P.C.
🇺🇸Bronx, New York, United States
Capital Cardiology Associates
🇺🇸Troy, New York, United States
Comprehensive Clinical Research
🇺🇸Berlin, New Jersey, United States
Triangle Medical Research Associates
🇺🇸Raleigh, North Carolina, United States
Wake Research Associates
🇺🇸Raleigh, North Carolina, United States
Piedmont Medical Research Associates
🇺🇸Winston-Salem, North Carolina, United States
Crescent Medical Research Associates
🇺🇸Salisbury, North Carolina, United States
Cedar Research LLC
🇺🇸Tacoma, Washington, United States
Anasazi Internal Medicine
🇺🇸Phoenix, Arizona, United States
Metrolina Medical Research
🇺🇸Charlotte, North Carolina, United States
Willamette Valley Clinical Studies
🇺🇸Eugene, Oregon, United States
Clinical Research Associates of Tidewater
🇺🇸Norfolk, Virginia, United States
Rainier Clinical Research Center Inc.
🇺🇸Renton, Washington, United States
Lynn Institute of Norman
🇺🇸Norman, Oklahoma, United States