to Evaluate the Safety and Efficacy of Pitavastatin in Patients With IFG and Hyperlipidemia
to Evaluate the Safety and Efficacy of Pitavastatin in Patients With IFG and Hyperlipidemia
Primary Objective

 : To evaluate that there is no different effect on HbA1c between routine lipid lowering
 therapy(Livalo 2mg) and intensive lipid lowering therapy(Livalo 4mg) in the hyperlipidemic
 patients with impaired fasting glucose (IFG).

 H0: µT-µC ≥ 0.4 vs H1: µT-µC < 0.4

 µT = the change of HbA1c in the test drug (Pitavastatin 4 MG) µC = the change of HbA1c in the
 control drug (Pitavastatin 2 MG)
Investigational Product Test group: Pitavastatin calcium (LIVALO) 4mg tab Control group:
 Pitavastatin calcium (LIVALO) 2mg tab

 Study Site: Multi-centers in Korea

 Period: For 24months after IRB approval at each site (Including 12months of subject
 enrollment period)

 Efficacy End points

 A. Primary end point The change of HbA1c before and after taking LIVALO

 B. Secondary end point

 1. Incidence of diabetes within 1year after registration (based; FPG ≥126mg/dL or to need
 taking diabetes medication)

 2. Incidence of major cardiovascular (TLR-MACE) events within 1 year after registration

 3. Incidence of total cardiovascular (TVR-MACE) events within 1 year after registration

 4. The change of the lipid composition (T-chol, TG, LDL-C, HDL-C, ApoA1/ApoB)

 5. The changes of hs-CRP

 6. The changes of Adiponectin

 7. The change of blood glucose and Insulin levels FPG(Fasting Plasma Glucose) Fasting Serum
 Insulin HOMA IR [fasting insulin(µIU/mL) X fasting glucose(mg/dL)]/405 HOMA β [360 X
 fasting insulin(µIU/mL)]/[fasting glucose(mg/dL)-63]

 Statistical Methods

 1. Efficacy A. Primary efficacy endpoint analysis Describe statistics of basic about the
 HbA1c variation before and after taking LIVALO by groups. In order to verify
 noninferiority of test drug, check that upper limit of confidence interval of the
 one-sided 97.5% is less than 0.4% about difference of HbA1c variation between the
 control group and the test group, before and after taking LIVALO.

 B. Secondary efficacy endpoint analysis Continuous variables

 :Present the mean, standard deviation, minimum, and maximum values for TC, TG, LDL-C,
 HDL-C, Fasting serum insulin, Fasting plasma glucose and HOMA IR, HOMA β etc. by each
 visit and in each group. In comparison with intergroup, using two-sample t-test for
 normal distribution and using Wilcoxon rank sum test for non-normal distribution. Also
 In comparison with the same group, using paired t-test for normal distribution and using
 Wilcoxon signed rank test for non-normal distribution.

 Discrete variables

 : The number and percentage of the subjects for incidence of DM and cardiovascular event
 are described of each group and the ratio of the intergroup comparison use χ2-test or
 Fisher's exact test.

 2. Safety All the AEs and the ADRs which manifested more than once are described by the
 frequency and percentage of each group and use χ2-test or Fisher's exact test for
 intergroup comparison about the rate of AEs and ADRs Laboratory tests and vital signs
 are analyzed descriptive statistics quantity of each group, and in comparison with
 intergroup, use two-sample t-test for normal distribution and use Wilcoxon rank sum test
 for non-normal distribution. Also, In comparison with the same group, use paired t-test
 for normal distribution and use Wilcoxon signed rank test for non-normal distribution.

 Clinical laboratory test is analyzed the frequency and percentage of the outside normal range
 of subjects, and using χ2-test or Fisher's exact test with intergroup.
Inclusion Criteria:

 1. Male and Female patients who are more than 20 years old or 70 years old or less.

 2. Patient who voluntarily sign on written informed consent form

 3. Patient who LDL-C ≥ 100mg/dl or was diagnosed with hyperlipidemia

 4. Patient who was suspected with Imparied Fasting Glucose (IFG) and satisfy FPG level ≥
 100mg/dL and < 126mg/dL when FPG measured twice.

 Exclusion Criteria:

 1. Patient who has familial hypercholesterolemia

 2. Patient who has been diagnosed with Type1, Type2 DM or secondary DM(diabetes mellitus)
 at the screening visit (Diagnostic criteria of DM: HbA1c≥ 6.5%)

 3. Patient who has received antidiabetic within 6weeks to the screening visit

 4. Patient who has been taking insulin continuously or to be needed in the future

 5. Patient who has a history of gastrectomy

 6. Patient who is suspected or diagnosed with malignant tumor within last 10 years

 7. Patient who has serious pancreatic disease or endocrine disorders

 8. Patient who currently takes Cyclosporine

 9. Patient who has a medical history of hypersensitivity to Pitavastatin calcium

 10. Patient who has suspected renal failure (serum creatinine ≥2.0 mg/dL)

 11. Patient who has suspected liver dysfunction (more than 2.5 times the upper limit of
 normal AST or ALT)

 12. Patient who has more than 3 times the upper limit of normal CPK

 13. Patient who is breastfeeding, pregnant or planning pregnancy

 14. Patient who deemed inappropriate as subject in the opinion of the Principal
 Investigator or Investigator