Hypercholesterolemia or Combined Dyslipidemia and 2 or more risk factors for coronary heart disease (CHD) MedDRA version: 7.1 Level: LLT Classification code 10020604
Conditions
Sponsors
Kowa Research Europe Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females (age range 18-75 years); 2. Non-pregnant, non-lactating females. Women of child bearing potential are allowed to enter the study ONLY if they use sustained contraceptive preparations (e.g., implants or intramuscular [IM] injections) or comply with an approved mechanical contraceptive method. 3. At least two cardiovascular disease risk factors have to be present: - Cigarette smoking; - Hypertension (blood pressure =140/90 mm Hg or on antihypertensive medication); - Low HDL-C (60 mg/dL at Visit 3 (week -1) or Visit 3A (if applicable) then the number of risk factors will be reduced by 1); - Age (men =45 years, women =55 years). 4. Patients who are eligible and able to participate in the study and who have given informed consent after the purpose and nature of the investigation has been explained to them; 5. In order to qualify for randomization at Visit 4 (Week 0), patients must have been following a fat and cholesterol restrictive diet as advised by the EAS during the dietary stabilization lead-in period (i.e. for at least 8 weeks for those patients previously taking lipid lowering medication and at least 6 weeks for those not previously taking lipid lowering medication). Patients must also agree not to eat grapefruit or drink grapefruit juice for the duration of the study; 6. In order to qualify for randomization at Visit 4 (Week 0), patients must present with primary hypercholesterolemia or combined dyslipidemia, as defined by elevated plasma LDL C (LDL C =3.4 mmol/L [130 mg/dL] =5.7 mmol/L [220 mg/dL]) despite dietary therapy and elevated TG levels of =4.6 mmol/L (400 mg/dL) at 2 visits during the dietary lead-in period. If these criteria are not satisfied at Visit 2 (Week –2) and Visit 3 (Week –1), or if the LDL C concentration of the lower qualifying specimen differs by =15% from the higher qualifying specimen, 1 additional lipid sample will be permitted for both variables 1 week after Visit 3 (Visit 3A) to enable the patient to qualify for randomization 7. Patients have to agree to be available for every clinic visit, which will occur in the morning. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Homozygous familial hypercholesterolemia (heterozygous component of familial hypercholesterolemia is acceptable for inclusion); 2. Any conditions which may cause secondary dyslipidemia. 3. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of any drug. 4. Any history of pancreatic injury or pancreatitis, or impaired pancreatic function/injury as indicated by abnormal lipase or amylase; 5. Liver injury, imparied renal function, uncontrolled diabetes mellitus 6. Current obstruction of the urinary tract or difficulty in voiding due to mechanical as well as inflammatory conditions, which is likely to require intervention during the course of the study or is regarded as clinically meaningful by the investigator; 7. Serum CK levels >5 x ULRR over the lead in period. For patients with unexplained serum CK >5 x ULRR at Visit 1 or 2, a repeat CK >5 x ULRR in the absence of conditions explaining the CK elevation is exclusionary; 8. Uncontrolled hypothyroidism. 9. Any severe acute illness or severe trauma in the last 3 months prior to Visit 1 (Week -8/-6); 10. Major surgery, during the 3 months prior to Visit 1 (Week -8/-6); 11. Significant CVD prior to randomization, such as myocardial infarction, coronary or peripheral artery angioplasty, bypass graft surgery or severe or unstable angina pectoris within the last 3 months; 12. Evidence of symptomatic heart failure (New York Heart Association [NYHA] class III or IV), gross cardiac enlargement (cardiothoracic ratio >0.5); significant heart block or cardiac arrhythmias. 13. Left ventricular (LV) ejection fraction 2 teaspoons Metamucil or psyllium containing supplement per day), or other dietary fiber supplements, fish oils, sterol/stanol products, or others at the discretion of the investigator; 23. History of hypersensitivity reactions to other HMG-CoA reductase inhibitors; 24. Any concomitant medication not permitted by this protocol (see Section 4.5.5, Concomitant Therapy); 25. History of being resistant to lipid-lowering m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To compare the efficacy of pitavastatin 4 mg QD vs. simvastatin 40 mg QD with respect to changes from baseline in other lipid and lipoprotein fractions (TC, HDL C, TC:HDL-C ratio, non-HDL:HDL ratio, TG, apolipoprotein B [Apo B] and apolipoprotein A1 [Apo-A1], , Apo-B:Apo-A1 ratio, high sensitivity C-reactive protein [hs-CRP], oxidized LDL, and LDL-C target attainment [European Atherosclerosis Society {EAS} and National Cholesterol Education Program {NCEP}]) To assess the safety and tolerability of pitavastatin 4 mg QD when administered for 12 weeks using an up-titration regimen. ;Main Objective: To demonstrate the non-inferiority of pitavastatin 4 mg once daily (QD) versus (vs.) simvastatin 40 mg QD, with respect to the reduction of LDL-C, when administered for 12 weeks using an up-titration regimen.;Primary end point(s): To demonstrate the non-inferiority of pitavastatin 4 mg once daily (QD) versus (vs.) simvastatin 40 mg QD. | — |
Countries
Denmark, Spain, Sweden, United Kingdom
Outcome results
None listed