Clinical trial NCT00459745: A Study to Evaluate Daily Pravastatin, Fenofibrate or Pravafen in the Treatment of Combined Hyperlipidemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Combined Hyperlipidemia
Keywords: Cardiovascular Disease
Fenofibrate
LDL cholesterol
HDL cholesterol
Hyperlipidemia
Pravastatin
Triglycerides
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
Collaborators: name: Integrium
First posted: 2007-04-12
Enrollment: 481
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

    -

Primary outcomes:
measure: 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.
timeFrame: bBaseline to 12 weeks
Secondary outcomes:
measure: 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
timeFrame: Baseline to 12 weeks
measure: 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
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Anasazi Internal Medicine
state: Arizona
city: Sierra Vista
country: United States
facility: Cochise Clinical Research
state: Arizona
city: Long Beach
country: United States
facility: Memorial Research Medical Clinic
state: California
city: Roseville
country: United States
facility: Clinical Trials Research
state: California
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jupiter
country: United States
facility: Drug Study Institute
state: Florida
city: Melbourne
country: United States
facility: Mima Century Research Associates
state: Florida
city: Ormond Beach
country: United States
facility: Cardiology Research Associates
state: Florida
city: Atlanta
country: United States
facility: Atlanta Vascular Research Foundation
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Evansville
country: United States
facility: Welborn Clinic Research Center
state: Indiana
city: Evansville
country: United States
facility: MediSphere Medical Research Center LLC
state: Indiana
city: Jeffersonville
country: United States
facility: Research Institute of Middle America
state: Indiana
city: Newburgh
country: United States
facility: Welborn Clinic Gateway
state: Indiana
city: Louisville
country: United States
facility: Lemarc Research Center
state: Kentucky
city: Louisville
country: United States
facility: Bluegrass Clinical Research, Inc.
state: Kentucky
city: Auburn
country: United States
facility: Androscoggin Cardiology Associates
state: Maine
city: Baltimore
country: United States
facility: MODEL Clinical Research
state: Maryland
city: Baltimore
country: United States
facility: Health Trends Research, LLC
state: Maryland
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: West Yarmouth
country: United States
facility: Clinical Research Center of Cape Cod, Inc
state: Massachusetts
city: Florissant
country: United States
facility: Clinical Study Site
state: Missouri
city: Manchester
country: United States
facility: Mercy Medical Group
state: Missouri
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Bronx
country: United States
facility: Bronx Nephrology Hypertension, P.C.
state: New York
city: Troy
country: United States
facility: Capital Cardiology Associates
state: New York
city: Charlotte
country: United States
facility: Metrolina Medical Research
state: North Carolina
city: Charlotte
country: United States
facility: Sensenbrenner Primary Care LLC
state: North Carolina
city: Raleigh
country: United States
facility: Triangle Medical Research Associates
state: North Carolina
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Salisbury
country: United States
facility: Crescent Medical Research Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Cincinnati
country: United States
facility: The Lindner Clinical Trial Center
state: Ohio
city: Hudson
country: United States
facility: Ohio Clinical Research
state: Ohio
city: Kettering
country: United States
facility: Wells Institute for Health Awareness
state: Ohio
city: Lyndhurst
country: United States
facility: Ohio Clinical Research, LLC
state: Ohio
city: Bartlesville
country: United States
facility: Bluestem Cardiology
state: Oklahoma
city: Norman
country: United States
facility: Lynn Institute of Norman
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Clinical Studies
state: Oregon
city: Fleetwood
country: United States
facility: Fleetwood Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Clinical Research, LLC
state: Pennsylvania
city: Reading
country: United States
facility: Southern Berks Family Medicine
state: Pennsylvania
city: Tipton
country: United States
facility: Tipton Medical Center
state: Pennsylvania
city: Mount Pleasant
country: United States
facility: Palmetto Medical Research Associates
state: South Carolina
city: Simpsonville
country: United States
facility: Upstate Pharmaceutical Research
state: South Carolina
city: Bristol
country: United States
facility: TriCities Medical Research Associates
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group
state: Tennessee
city: Austin
country: United States
facility: Clinical Trials Research
state: Texas
city: San Antonio
country: United States
facility: Texas Medical Research LLC
state: Texas
city: Norfolk
country: United States
facility: Hampton Roads Center for Clinical Research
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research
state: Virginia
city: Renton
country: United States
facility: Rainier Clinical Research Center Inc.
state: Washington
city: Tacoma
country: United States
facility: Cedar Research LLC
state: Washington
Study officials:
References: