BACKGROUND A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia.

OBJECTIVE The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea.

METHODS Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal.

RESULTS A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88).

CONCLUSIONS There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.