Efficacy and tolerability of a generic and a branded formulation of atorvastatin 20 mg/d in hypercholesterolemic Korean adults at high risk for cardiovascular disease: A multicenter, prospective, randomized, double-blind, double-dummy clinical trial
Kim S.-H.,Seoul National University |
Kim S.-H.,Seoul Metropolitan Boramae Hospital |
Park K.,Seoul National University |
Hong S.-J.,Korea University |
And 8 more authors.
Clinical Therapeutics | Year: 2010
Background: The reduction in plasma LDL-C concentrations with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has been reported to reduce cardiovascular risk and mortality in individuals with or without preexisting coronary artery disease and elevated LDL-C concentrations. Atorvastatin is a statin used for lowering LDL-C concentrations. A generic formulation of atorvastatin is being developed in Korea. This study was undertaken for the purposes of marketing the generic formulation.Objective: This study was designed to compare the efficacy and tolerability of a generic formulation of atorvastatin 20 mg/d versus a branded formulation at the same dosage in hypercholesterolemic Korean adults at high risk for cardiovascular events.Methods: This 8-week, multicenter, randomized, double-blind, double-dummy study was conducted at 10 clinical centers in Korea between September 2008 and May 2009. Male and female patients aged 20 to 85 years at high risk for cardiovascular events (defined as an elevated LDL-C concentration [≥100 mg/dL]) were enrolled. Eligible patients were randomly assigned to receive generic or branded atorvastatin 20 mg once daily for 8 weeks. The primary end point was the percentage change from baseline to 8 weeks in LDL-C concentration. Secondary end points were the percentage changes from baseline in total cholesterol (TC), triglycerides (TG), HDL-C, apolipoprotein (apo) A1 and B, and high-sensitivity C-reactive protein concentrations; small, dense LDL (sdLDL) fraction; and tolerability. Tolerability was assessed using physical examination, laboratory testing, and by recording adverse events (AEs) at each visit. An additional secondary end point was the proportion of patients who achieved an LDL-C goal of <100 mg/dL.Results: A total of 244 patients were randomized to treatment, and 33 patients were withdrawn from the study (9 patients did not receive the study medication, 11 patients due to AEs, and 13 patients due to withdrawal of consent). A total of 211 patients completed the study (50.7% male; 100% Asian; mean [SD] age, 61.7 [9.2] years) (106 patients in the group that received Accepted for publication October 5, 2010. the generic formulation and 105 patients in the group that received the branded formulation). LDL-C concentrations were reduced from the baseline by 44% and 46% after 8 weeks of treatment with the generic and branded formulations, respectively (P = NS). The percentage changes from baseline to study end in HDL-C, TC, TG, apo A1, apo B, and hsCRP concentrations and sdLDL fraction the proportions of patients who achieved the LDL-C goal between the 2 groups did not reach statistical significance. The most commonly reported events were hepatobiliary laboratory abnormality (1.7%), general somatic discomfort (1.7%), and epigastric pain (0.8%) in the group that received the generic formulation, and myalgia (1.7%), epigastric pain (0.9%), and elevation of creatinine phosphokinase (0.9%) in the group that received the branded formulation. No serious AEs were reported in either group.Conclusions: After 8 weeks of treatment, the differences in the LDL-C-lowering effects between the generic and branded formulations of atorvastatin 20 mg/d did not reach statistical significance in these Korean patients at high risk for cardiovascular events. Both formulations were generally well tolerated. © 2010 Excerpta Medica Inc.
Fischer E.-M.,Stvincent Hospital |
Patsch J.,Stvincent Hospital |
Muschitz C.,Stvincent Hospital |
Becker S.,Orthopedic Hospital |
Resch H.,Stvincent Hospital
Gynecological Endocrinology | Year: 2011
Objective. We report about a 49-years-old patient with severe osteoporosis and multiple vertebral fractures after male-to-female reassignment therapy. The patient had 12 years of hormone replacement therapy (HRT) with very low serum levels of estradiol and testosterone at the time the fractures occurred. The reasons are currently not known. Most likely the patient seems to be non-compliant with the HRT intake. Results. Bone mineral density (BMD) measurements showed highly decreased T-Scores between -3.5 and -4.5. All routine laboratory parameters, especially the markers of bone turnover, were within the normal range. μ-CT 3D-structural analysis of the bone biopsy showed a highly reduced trabecular connectivity (Conn.Dens.). Bone mineral density distribution (BMDD), measured by quantitative backscattered electron imaging (qBEI), showed a BMDD within normal range, except heterogeneity index (CaWIDTH) and fraction of highly mineralised bone (CaHIGH), which were increased. Conclusions. We conclude that our patient has a cross-sex hormonal therapy induced total imbalance of bone homeostasis, because of the long lasting under monitored hormone therapy which led to severe interferences in physiological maturities. Male-to-female transsexuals without an adequate estrogen treatment are at increased risk of developing osteoporosis. © 2011 Informa UK, Ltd.