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

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.

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.

Study Overview

• Status: Completed
• Conditions: Combined Hyperlipidemia
• Intervention / Treatment: Drug: Pravastatin; Drug: Fenofibrate; Drug: Pravafen

• Study Type: Interventional
• Enrollment (Actual): 481
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Anasazi Internal Medicine
    • Sierra Vista, Arizona, United States, 85635
      • Cochise Clinical Research
  • California
    • Long Beach, California, United States, 90806
      • Memorial Research Medical Clinic
    • Roseville, California, United States, 95661
      • Clinical Trials Research
    • Tustin, California, United States, 92780
      • Orange County Research Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Jacksonville, Florida, United States, 32205
      • Jacksonville Center for Clinical Research
    • Jupiter, Florida, United States, 33458
      • Drug Study Institute
    • Melbourne, Florida, United States, 32901
      • MIMA Century Research Associates
    • Ormond Beach, Florida, United States, 32174
      • Cardiology Research Associates
  • Georgia
    • Atlanta, Georgia, United States, 30084
      • Atlanta Vascular Research Foundation
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Medisphere Medical Research Center LLC
    • Evansville, Indiana, United States, 47713
      • Welborn Clinic Research Center
    • Jeffersonville, Indiana, United States, 47130
      • Research Institute of Middle America
    • Newburgh, Indiana, United States, 47630
      • Welborn Clinic Gateway
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • Bluegrass Clinical Research, Inc.
    • Louisville, Kentucky, United States, 40213
      • Lemarc Research Center
  • Maine
    • Auburn, Maine, United States, 04210
      • Androscoggin Cardiology Associates
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • MODEL Clinical Research
    • Baltimore, Maryland, United States, 21208
      • Health Trends Research, LLC
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
  • Massachusetts
    • West Yarmouth, Massachusetts, United States, 02673
      • Clinical Research Center of Cape Cod, Inc
  • Missouri
    • Florissant, Missouri, United States, 63031
      • Clinical Study Site
    • Manchester, Missouri, United States, 63021
      • Mercy Medical Group
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • New York
    • Bronx, New York, United States, 10467
      • Bronx Nephrology Hypertension, P.C.
    • Troy, New York, United States, 12180
      • Capital Cardiology Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • Metrolina Medical Research
    • Charlotte, North Carolina, United States, 28277
      • Sensenbrenner Primary Care LLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Raleigh, North Carolina, United States, 27609
      • Triangle Medical Research Associates
    • Salisbury, North Carolina, United States, 28144
      • Crescent Medical Research Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Medical Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Hudson, Ohio, United States, 44236
      • Ohio Clinical Research
    • Kettering, Ohio, United States, 45429
      • Wells Institute for Health Awareness
    • Lyndhurst, Ohio, United States, 44124
      • Ohio Clinical Research, LLC
  • Oklahoma
    • Bartlesville, Oklahoma, United States, 74006
      • BlueStem Cardiology
    • Norman, Oklahoma, United States, 73071
      • Lynn Institute of Norman
  • Oregon
    • Eugene, Oregon, United States, 97404
      • Willamette Valley Clinical Studies
  • Pennsylvania
    • Fleetwood, Pennsylvania, United States, 19522
      • Fleetwood Clinical Research
    • Philadelphia, Pennsylvania, United States, 09114
      • Philadelphia Clinical Research, LLC
    • Reading, Pennsylvania, United States, 19606
      • Southern Berks Family Medicine
    • Tipton, Pennsylvania, United States, 16684
      • Tipton Medical Center
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Palmetto Medical Research Associates
    • Simpsonville, South Carolina, United States, 29681
      • Upstate Pharmaceutical Research
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • TriCities Medical Research Associates
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
  • Texas
    • Austin, Texas, United States, 78705
      • Clinical Trials Research
    • San Antonio, Texas, United States, 78238
      • Texas Medical Research LLC
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater
    • Norfolk, Virginia, United States, 23502
      • Hampton Roads Center for Clinical Research
    • Richmond, Virginia, United States, 23294
      • National Clinical Research
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center Inc.
    • Tacoma, Washington, United States, 98405
      • Cedar Research Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pravastatin; Pravastatin 40 mg	Drug: Pravastatin; Other Names: Pravachol
Active Comparator: Fenofibrate; Fenofibrate 160 mg	Drug: Fenofibrate
Experimental: Pravafen (Parvastatin and Fenofibrate); Combined Therapy of Pravastatin 40 mg and Fenofibrate 160 mg.	Drug: Pravafen; Other Names: Combination of Pravastatin 40 mg and Fenofibrate 160 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Change in HDL	bBaseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Changes in TC, TG, LDL-C, HDL-C and TC/HDL-C	Baseline to 12 weeks
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	Changes in ALT, AST and CK and overall safety	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Shionogi
• Collaborators: Integrium

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 9, 2007
• First Submitted That Met QC Criteria: April 11, 2007
• First Posted (Estimate): April 12, 2007

Study Record Updates

• Last Update Posted (Actual): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Hyperlipidemia; Pravastatin; HDL cholesterol; Triglycerides; LDL cholesterol; Fenofibrate
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipidemias; Hyperlipoproteinemias; Hyperlipidemia, Familial Combined; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin; Fenofibrate
• Other Study ID Numbers: Sc-PRAVA-06-02