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.
Overview
- Phase
- Phase 3
- Intervention
- Pravastatin
- Conditions
- Combined Hyperlipidemia
- Sponsor
- Shionogi
- Enrollment
- 481
- Locations
- 55
- Primary Endpoint
- 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.
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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,
Arms & Interventions
Pravastatin
Pravastatin 40 mg
Intervention: Pravastatin
Fenofibrate
Fenofibrate 160 mg
Intervention: Fenofibrate
Pravafen (Parvastatin and Fenofibrate)
Combined Therapy of Pravastatin 40 mg and Fenofibrate 160 mg.
Intervention: Pravafen
Outcomes
Primary Outcomes
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.
Time Frame: bBaseline to 12 weeks
Change in HDL
Secondary Outcomes
- 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)
- 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)