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Purpose: This study aimed to compare the efficacy and safety of generic and branded irbesartan for 8 weeks in patients with mild-to-moderate essential hypertension., Patients and Methods: We screened 221 patients with mild-to-moderate hypertension. After exclusion per study criteria, 177 subjects were randomized to receive 150 mg generic irbesartan (n=91) or branded irbesartan (n=86) as the intention to treat set. The primary efficacy endpoint of this study was the change in mean sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks between the generic and branded irbesartan groups. The secondary efficacy endpoints were the change in mean SiDBP at Week 4 from baseline and the change in mean sitting systolic blood pressure (SiSBP) at Weeks 4 and 8 from baseline in both groups. All safety issues were evaluated., Results: At Week 8, the generic and branded irbesartan groups showed significantly reduced SiDBP (-10.3±8.0, -10.7±7.7 mmHg, all P <0.0001) compared with baseline values, and the mean between-group difference in SiDBP change after 8 weeks of treatment was -0.4±1.2 mmHg, showing the non-inferiority of generic irbesartan vs branded irbesartan. Furthermore, secondary efficacy, which was the mean change of SiDBP from baseline at 4 weeks, was comparable between the two groups (-9.4±8.1 vs -9.9±7.4 mmHg, P =0.69). There were no between-group differences in mean changes of SiSBP after 4 or 8 weeks of treatment ( P =0.78, P =0.97, respectively), or in the incidence of adverse effects (16.7 vs 24.4%, P =0.20)., Conclusion: Generic irbesartan treatment in patients with mild-to-moderate essential hypertension has shown effective antihypertensive effects comparable with the branded irbesartan treatment, with similar incidence of adverse effects., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Acetyl-L-carnitine (ALC) has demonstrated neuroprotective effects in several experiments and is widely prescribed to reduce cognitive impairment in Alzheimer's disease patients or manage neuropathic symptoms in diabetic patients., Objectives: This study was designed to assess the pharmacokinetic (PK) bioequivalence between a new generic (test) formulation of ALC hydrochloride 590 mg and a branded (reference) formulation of ALC hydrochloride 590 mg in healthy Korean male volunteers., Methods: This was a randomizedsequence, single-dose, two-way crossover study. All subjects randomly received one formulation of the test or reference tablet and the other formulation with a 7-day washout period. Blood samples (7 mL) were collected immediately before dosing, and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours postdose. The plasma concentrations of ALC were analyzed using liquid chromatography tandem mass spectrometry. Tolerability was assessed throughout the study., Results: The PK profiles of both formulations showed similar rends. The mean (±SD) baseline (predose) concentration of ALC was 1.23±0.31 μg/mL and 1.09±0.30 μg/mL for the test and the reference formulations, respectively. The mean Cmax for the test and reference formulations were 1.74±0.43 μg/mL and 1.68±0.48 μg/mL, respectively. The mean AUClast of ALC was 12.96±1.89 μg×h/mL and 12.49±2.44 μg×h/mL for the test and reference formulations, respectively. The geometric mean ratios of test/reference (90% CI) were 1.050 (0.960-1.149) for Cmax and 1.048 (1.000-1.099) for AUClast. Both formulations were well tolerated in all treatment groups., Conclusion: The test and the reference formulations of ALC were bioequivalent with regard to the PK parameters.

Background: Tianeptine is widely used for controlling depressive symptoms., Objective: The aim of this study was to evaluate the bioequivalence between the generic (test) formulation containing tianeptine sodium 12.5 mg and the branded (reference) formulation Stablon® with regard to their pharmacokinetic profiles., Methods: A randomized, two-sequence, two-treatment crossover study was conducted in healthy male Korean volunteers. All of the enrolled subjects were allocated to one of two sequence groups. They were administered a tablet of the test or reference formulation and then administered the alternative formulation after a 7-day washout period. The blood samples were taken before dosing and at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, and 10 hours after dosing. The plasma concentrations of tianeptine were analyzed using high-performance liquid chromatography with tandem mass spectrometer. Tolerability was assessed throughout the study., Results: The pharmacokinetic parameters were assessed in the 40 subjects who completed the study. The tianeptine C(max) for the test formulation was 283.13 ± 57.58 ng/mL (mean ± SD) and that for the reference formulation was 272.50 ± 59.00 ng/mL. The AUC(last) of tianeptine was 803.24 ± 180.94 ng×h/mL for the test formulation and 792.27 ± 180.93 ng×h/mL for the reference formulation. The geometric mean ratio (%) of the test to reference formulation was 104.04 (90% CI, 99.66 - 108.61) for C(max) and 101.30 (98.01 - 104.71) for AUC(last). Clinically significant adverse events were not reported during the study., Conclusion: The test and reference formulations of tianeptine were bioequivalent with regard to the pharmacokinetic parameters of Cmax and AUC(last). Both formulations were tolerated by all of the participants.

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., (Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.)

Background: Bicalutamide is an oral nonsteroidal antiandrogenic drug used in the treatment of prostate cancer. A new generic 50-mg tablet formulation of bicalutamide has recently been developed., Objective: This study evaluated the relative bioavailability and tolerability of the new generic formulation of bicalutamide 50-mg tablets (test) and the currently marketed formulation (reference) in healthy Korean male subjects. The study was conducted to meet Korean regulatory requirements for authorization to market the generic formulation., Methods: This was a randomized-sequence, open-label study in which healthy Korean male subjects (aged 20-55 years) received single doses of the test and reference formulations in a 2-period crossover fashion, with a 6-week washout period between doses. Blood samples for the determination of plasma bicalutamide concentrations were obtained at regular intervals over 672 hours after dose administration. Pharmacokinetic parameters were determined using noncompartmental methods. Relative bioavailability was evaluated by comparing the log-transformed C(max) and AUC(0-672) of the 2 formulations; Korean regulatory requirements for the assumption of bioequivalence were met if the 90% CIs fell within the range of 0.80 to 1.25. Tolerability was assessed based on physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and adverse events (AEs) (spontaneously reported or observed by investigators)., Results: Of 47 volunteers screened for inclusion, 38 were enrolled and 32 completed the study (mean [SD] age, 24.9 [3.7] years; mean height, 173.8 [6.2] cm; mean weight, 66.1 [7.1] kg). Median T(max) was 24 hours for both formulations. The C(max) of the test and reference formulations was 1176.2 (191.6) and 1118.9 (209.5) μg/L, respectively. The corresponding values for AUC(0-672) were 277,503 (66,865) and 271,961 (75,597) μg · h/L. The 90% CIs for the geometric mean ratios of log-transformed C(max) and AUC(0-672) were 1.00 to 1.11 and 0.99 to 1.07, respectively. Thirty-three AEs were reported, including 17 events in 9 subjects who received the test formulation and 16 events in 12 subjects who received the reference formulation. All AEs were mild, and no subjects discontinued the study because of AEs., Conclusions: In this single-dose study in healthy Korean male subjects, the pharmacokinetic parameters of the new generic formulation of bicalutamide 50-mg tablets did not differ significantly from those of the reference formulation. The new generic formulation met Korean regulatory criteria for the assumption of bioequivalence to the currently marketed formulation. Both formulations were well tolerated. Korea Food and Drug Administration registration number: PSPD 3057., (Copyright © 2010 Elsevier HS Journals, Inc. All rights reserved.)