Efficacy and Safety Study of Pitavastatin for Hypercholesterolemia

1PC002 is a newly developed synthetic and highly potent HMG-CoA reductase inhibitor. Its active compound, pitavastatin has recently been approved by US FDA for indications of primary hypercholesterolemia and combined dyslipidaemia. It exhibits unique pharmacokinetic properties. Unlike atorvastatin which is metabolized by CYP3A4, metabolism of 1PC002 does not depend on CYP3A4. This multi-center study is conducted to confirm the efficacy and safety of 1PC002 administered for 12 weeks is non-inferior to atorvastatin.

This is a prospective, active-controlled, double-blind, randomized, parallel, and multi-center study. To target 150 evaluable subjects, approximately 200 Taiwanese patients with primary hypercholesterolemia or combined dyslipidemia will be enrolled in this study.

After providing the written inform consent, patients will undergo a complete physical examination, vital sign (brachial BP / HR), medical history, and lab assessment, including fasting serum LDL-C, TC, HDL-C, TG, and non-HDL. They should not take any hypolipidemic drugs for at least 4 weeks prior to initiation of study treatment. All eligible subjects will be randomized into 2 groups in a 1:1 ratio to receive either 2 mg 1PC002 or 10 mg atorvastatin once daily for 12 weeks.

* Study Group: 1PC002 1 cap. q.d. p.o.
* Control Group: Atorvastatin 1 cap. q.d. p.o.

After entering the baseline visit, lipid profiles (including fasting serum LDL-C, TC, HDL-C, TG, non-HDL, Apo A1, Apo B and Apo B / Apo A1 ratio), hs-CRP, eGFR, spot urinary albumin / creatinine ratio (ACR) and central BP values will be obtained at baseline, Week 4 and Week 12 for evaluating the effectiveness of study drugs and for any possible changes in laboratory data. Non-HDL value will be calculated by subtracting HDL-C from TC. Moreover, serum Cystatin C, another biomarker of renal function, will also be assessed at baseline and Week 12.

For monitoring the safety, biochemical and hematological assessment will be performed at baseline, Week 4 and 12. Additional liver function and CK test will be conducted at Week 8. The occurring AE(s) and SAE will be followed until resolution or the event is considered stable.

Eligibility Criteria:
Inclusion Criteria:

1. Females or males aged between 20 and 80 years.
2. Subjects who meet All of the following diagnosis at screening visit:

   * Primary hypercholesterolemia or combined dyslipidemia
   * TC ≥ 220 mg/dL or LDL-C ≥ 130 mg/dL
   * TG \< 400 mg/dL
3. Subjects who is willing and able to provide ICF.

Exclusion Criteria:

1. Females who are pregnant, breast-feeding or intent to be pregnant during study period, or those of childbearing potential not using effective contraception.
2. Subject with documented homozygous familial hypercholesterolemia.
3. Subject with documented HIV.
4. Subject with documented hypothyroidism and inadequate treatment judged by investigator.
5. Subjects with unstable cardiovascular disease (CVD) prior to randomization.
6. Subjects with hepatic or biliary disorders, such as acute hepatitis, acute exacerbation of chronic hepatitis, liver cirrhosis, liver cancer and jaundice.
7. Any condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.
8. Subjects with the following lab data at screening visit:

   * serum creatine kinase (CK) \> 5 x upper limit of normal (ULN)
   * ALT or AST of \> 3 x ULN
   * serum creatinine ≥ 1.5 mg/dL
   * HbA1c \> 8.0%
9. Subject with the following past histories:

   * hypersensitivity to statins or any other ingredients of study drugs
   * resistant to statins treatment
10. Use of any lipid-lowering agents within 4 weeks prior to the initiation of study treatment.
11. Use of any investigational product within 4 weeks prior to screening.
12. Any unstable concomitant disease or clinical condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk to participate in the study or confounds the ability to interpret data from the study.