Safety and effectiveness of 4-week therapy with aceclofenac controlled release once a day.

Aceclofenac controlled-release (CR) is a once-a-day tablet with 200 mg of aceclofenac, and is bioequivalent to conventional aceclofenac. However, its safety in humans has not been well studied in Korea. Therefore, we aimed to evaluate the overall incidence and patterns of adverse events (AEs), the effectiveness of aceclofenac CR, and the differences in incidence rates of the AEs based on each patient's baseline charateristics. This study was conducted on patients receiving aceclofenac CR in clinical practice at each investigational institution to treat musculoskeletal pain and inflammation. The subjects were administered one tablet of aceclofenac CR (200 mg once-a-day) and were observed for 4 weeks post-administration. Factors affecting the occurrence of AEs were evaluated, and the Visual Analogue Scale (VAS) was used to measure the pain intensity. Among 14,543 subjects, the incidence rate of AEs was 0.86%, and that of adverse drug reactions was 0.74%. No serious AEs and unexpected adverse drug reactions were monitored. The incidence rates of AEs were significantly higher in females, inpatient treatment, individuals with concurrent disorders, and those receiving concomitant medications, respectively (all P < 0.05). Four weeks post-using aceclofenac CR, the mean changes in VAS was significantly decreased compared to prior administration. The overall clinical efficacy rate was 91.63%. This study confirmed that no severe adverse reactions were observed for aceclofenac CR exceeding those previously reported for safety results of conventional formulation of this drug in routine clinical practice settings. The use of aceclofenac CR might not violate the previously reported information on the safety and effectiveness of aceclofenac.

Abietic acid alleviates endoplasmic reticulum stress and lipid accumulation in human primary hepatocytes through the AMPK/ORP150 signaling.

Abietic acid (AA), the main component of pine resin that has been traditionally used as Asian medicine, has been reported to demonstrate anti-inflammatory activities. Despite this, little is known about the effects of AA on hepatic endoplasmic reticulum (ER) stress and lipid metabolism. This study investigated the impacts of AA on ER stress and steatosis in in vitro obesity models. We found that Treatment with AA reduced lipid deposition and lipogenesis-related proteins expression in human primary hepatocytes. Augmented expression of ER stress markers (phospho-eukaryotic initiation factor-2α (eIF2α) and C/EBP homologous protein (CHOP)) in palmitate-treated hepatocytes were reversed by AA treatment. Further, AA treatment increased the expression of phospho-AMPK and oxygen-regulated protein 150 (ORP150) in hepatocytes. siRNA-associated knockdown of AMPK or ORP150 expression reduced the effects of AA on not only hepatic ER stress but also lipogenesis and apoptosis. These results denote that AA attenuates lipid accumulation in hepatocytes in the presence of palmitate through the suppression of ER stress by AMPK/ORP150 signaling. AA could be a potential candidate for treating non-alcoholic fatty liver disease.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Efficacy and Safety of UI05MSP015CT in Functional Dyspepsia: A Randomized, Controlled Trial.

Background/Aims: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). Methods: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. Results: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were -9.69±6.44 and -10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, -1.75 to 2.41), demonstrating non-inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. Conclusions: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD.