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

Combined Hyperlipidemia Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459745
• Other study ID #: Sc-PRAVA-06-02
• Status: Completed
• Phase: Phase 3
• First received: April 9, 2007
• Last updated: April 20, 2018
• Start date: April 2007
• Est. completion date: July 2009

Study information

• Verified date: August 2010
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 481
• Est. completion date: July 2009
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Combined Hyperlipidemia
• Hyperlipidemia, Familial Combined
• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

Drug:
• Pravafen

• Pravastatin

• Fenofibrate

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Shionogi	Integrium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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