PRIMARY HYPERCHOLESTEROLEMIA OR COMBINED DYSLIPIDEMIA 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 18-75 years). Non-pregnant, non-lactating females; 2. 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. A woman is considered to be of childbearing potential unless she is post hysterectomy or at least 1-year post-menopausal or post-tubal ligation. All women of child bearing potential must have a negative pregnancy test at the beginning of the dietary lead-in period (Visit 1/Week 8/ 6), and before initiating active treatment (Visit 4/Week 0); 3. 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; 4. In order to qualify for randomization, 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; 5. 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 [ mean LDL C =4.2 mmol/L (160 mg/dL) = 5.7 mmol/L (220 mg/dL) with the lower qualifying value being within 15% of he higher qualifying measurement] despite dietary therapy and elevated TG levels of = 4.6 mmol/L (400 mg/dL) at both consecutive visits (Visit 2 and 3 or Visits 3 and 3A as applicable) 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; and 6. Patients who 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) or familial hypoalphalipoproteinemia 2. Any conditions which may cause secondary dyslipidemia 3. Uncontrolled diabetes mellitus as defined by glycosylated hemoglobin A1c (HbA1c) >8%. 4. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. 5. Any history of pancreatic injury or pancreatitis, or impaired pancreatic function/injury as indicated by abnormal lipase or amylase 6. Liver injury as indicated by serum transaminase levels (ALAT/serum glutamic pyruvic transminase (SGPT), ASAT/serum glutamic oxaloacetic transminase (SGOT) >1.5 x upper limit of the reference range (ULRR) over the lead in period. 7. Impaired renal function as indicated by serum creatinine levels >1.5 x ULRR at Visit 1 (Week –8/-6). 8. 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; 9. Serum CK >5 x ULRR without clinical explanation. 10. Uncontrolled hypothyroidism defined as TSH > ULRR. 11. Any severe acute illness or severe trauma in the last 3 months prior to Visit 1 (Week 8/ 6); 12. Major surgery, during the 3 months prior to Visit 1 (Week 8/ 6); 13. Significant CVD prior to randomization such as myocardial infarction, coronary or peripheral artery angioplasty, bypass graft surgery, or severe or unstable angina pectoris. 14. 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 arrhythmia 15. Left ventricular (LV) ejection fraction 10 years. Patients with prior history of basal cell carcinoma or squamous cell carcinoma of the skin remain eligible if they have been cancer free for >5 the past years; 22. Within the last 2 years, a history of drug abuse or continuous consumption of more than 65 mL pure alcohol per day 23. Exposure to any investigational new drug within 30 days of study entry 24. Current or recent (within 4 weeks of Visit 1/Week 8/ 6) use of supplements known to alter lipid metabolism e.g. soluble fibers (including >2 teaspoons Metamucil or psyllium containin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the non-inferiority of pitavastatin 2 mg once daily (QD) versus (vs.) simvastatin 20 mg QD and pitavastatin 4 mg QD vs. simvastatin 40 mg, with respect to the reduction of LDL-C, when administered for 12 weeks using an up titration regimen for the higher doses (i.e., 4 mg pitavastatin and 40 mg simvastatin).;Secondary Objective: To compare the efficacy of pitavastatin 2 mg QD vs. simvastatin 20 mg QD and 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, Apo B and apolipoprotein A1 [Apo-A1], Apo-B:Apo-A1 ratio, high sensitivity C-reactive protein (hs-CRP), and LDL-C target attainment [European Atherosclerosis Society {EAS} and National Cholesterol Education Program {NCEP}]); andTo assess the safety and tolerability of pitavastatin 2 mg QD and pitavastatin 4 mg QD when administered for 12 weeks using an up titration regimen for the higher doses (i.e., 4 mg pitavastatin and 40 mg simvastatin). ;Primary end point(s): To demonstrate the non-inferiority of pitavastatin 2 mg versus (vs.) simvastatin 20 mg and pitavastatin 4 mg vs. simvastatin 40 mg | — |
Countries
Finland, Italy, United Kingdom
Outcome results
None listed