Efficacy and Safety of Pitavastatin/Ezetimibe Fixed-Dose Combination vs. Pitavastatin: Phase III, Double-Blind, Randomized Controlled Trial.

AIM: We compared the efficacy and safety of pitavastatin/ezetimibe fixed-dose combination with those of pitavastatin monotherapy in patients with hypercholesterolemia. METHODS: This trial was a multicenter, randomized, double-blind, active-controlled, parallel-group trial. A total of 293 patients were randomly assigned into four groups receiving 2 mg pitavastatin, 4 mg pitavastatin, 2 mg pitavastatin/10 mg ezetimibe (K-924 LD), and 4 mg pitavastatin/10 mg ezetimibe (K-924 HD) once daily for 12 weeks. RESULTS: The percentage changes in low-density lipoprotein cholesterol (LDL-C), the primary endpoint, were -39.5% for 2 mg pitavastatin, -45.2% for 4 mg pitavastatin, -51.4% for K-924 LD, and -57.8% for K-924 HD. Compared with pitavastatin monotherapy, the pitavastatin/ezetimibe fixed-dose combination significantly reduced LDL-C, total cholesterol, and non-high-density lipoprotein cholesterol. Meanwhile, the cholesterol synthesis marker, lathosterol, was significantly decreased with pitavastatin monotherapy and the pitavastatin/ezetimibe fixed-dose combination, although the decrease was attenuated in the latter. On the other hand, the cholesterol absorption markers, beta-sitosterol and campesterol, were reduced with the fixed-dose combination but not with pitavastatin monotherapy. The incidence of adverse events and adverse drug reactions was not significantly different between the two groups receiving the fixed-dose combination and monotherapy. The mean values of laboratory tests that are related to liver function and myopathy increased but remained within the reference range in all groups. CONCLUSIONS: The pitavastatin/ezetimibe fixed-dose combination showed an excellent LDL-C-reducing effect by the complementary pharmacological action of each component, and its safety profile was similar to that of pitavastatin monotherapy (ClinicalTrials.gov Identifier: NCT04289649).

A novel enzyme-linked immunosorbent assay specific for high-molecular-weight adiponectin.

Human plasma contains at least three forms of adiponectin: a trimer, a hexamer, and a high-molecular-weight (HMW) multimer. We purified HMW adiponectin from human plasma using its affinity to gelatin and obtained monoclonal antibodies against it. On Western blot analysis, the reactivity of these monoclonal antibodies was shown to be restricted to a non-heat-denatured form of adiponectin molecules. On heating, the collagen-like domain of adiponectin molecules became denatured, and thus the trimer form could not be maintained. From these, monoclonal antibodies against HMW adiponectin were suggested to react with the intact trimer of adiponectin. With these monoclonal antibodies, we developed a sandwich ELISA system for quantifying adiponectin in human serum. Its specificity was verified by analysis of serum fractions separated by gel-filtration chromatography, and our ELISA system was found to be HMW adiponectin-specific. With this novel ELISA, the HMW adiponectin concentrations were 8.4 +/- 5.5 microg/ml (mean +/- SD) in healthy women and 6.2 +/- 3.6 microg/ml in healthy men. Also, serum with a lower HMW adiponectin concentration was shown to have a lower HMW ratio (i.e., HMW adiponectin/total adiponectin).