Drugs in R & D最新文献

Background and Objective

Adult-onset Still’s disease (AOSD) is a recognized autoinflammatory disorder of unknown etiology. The standard initial management for AOSD includes conventional corticosteroids and disease-modifying antirheumatic drugs. In cases that are resistant to these treatments, additional therapeutic options such as immunosuppressants, biologics, and other alternative treatments may be considered. Yet, a significant proportion of patients remain unresponsive to these therapeutic interventions. Herein, a case is reported involving a patient with AOSD who had persistent pruritic lesions that did not respond to conventional therapy, but were alleviated with Janus kinase inhibitors (JAKi), namely baricitinib and upadacitinib. The objective is to expand the number of refractory AOSD cases treated with JAKi in clinical practice. Another aim is to offer potentially effective therapeutic options for AOSD patients who experience persistent pruritus.

Methods

A case was reported involving AOSD characterized by persistent pruritic lesions that failed to respond to conventional treatment, but showed favorable outcomes with JAKi therapy. An analysis of the PubMed literature was performed to assess the medication’s efficacy and explore possible mechanisms.

Results

The present case study is one of the few documented instances exploring the use of JAKi for treating AOSD, aligning with previously published research. After initiating JAKi therapy, the patient exhibited significant improvement in symptoms, most notably a reduction in persistent pruritus. Additionally, there was a substantial decrease in the patient’s glucocorticoid dosage. Aside from minor renal function anomalies, no adverse reactions were observed.

Conclusions

The present case illustrates that JAKi can provide rapid and sustained clinical improvement in patients with AOSD, especially those who have not responded to conventional treatment, and they have the ability to alleviate persistent itching. Further investigation is needed to ascertain the precise mechanism.

Clinical trials on innovative drugs in China have witnessed a stage of rapid development in recent years. The introduction of a number of government policies has stimulated enthusiasm for research and development in the pharmaceutical industry. We analyzed the data of the early-phase clinical trials registered in the Chinese Center for Drug Evaluation (CDE) from September 6, 2013, to December 31, 2022. All related registration information disclosed on the CDE website, including posted time, drug classification, dosing formula, indications, trial design, and trial status, were summarized and analyzed. A total of 5336 early-phase clinical trials were identified. The quantity and growth rate of early-phase clinical trials have increased substantially each year. Chemical drugs accounted for the largest proportion of early-phase clinical trials, although it dropped from 85.7% in 2013 to 59.5% in 2022. Moreover, the number of oncology drugs has increased yearly, accounting for 49.2% of all early-phase clinical trials in 2022. We can conclude that during 2013–2022, the development of early-phase clinical trials has progressed due to government support and advanced development techniques. To enhance the efficiency and success rate of early-phase clinical trials in the future, it is necessary to acquire advanced technical support and improve standardized supervision systems.

Background and Objective

Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters.

Patients and Methods

Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC–MS/MS) to evaluate ornidazole contents. maximum plasma concentration (C_max), time to C_max (T_max), the area under the curve (AUC) from t = 0 to infinity (AUC_0–∞), AUC from t = 0 to the last quantifiable concentration (AUC_0–t), half-life (t_1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure).

Results

For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC_0–t, C_max, and AUC_0–∞ were 100.97% (99.12–102.85%), 99.88% (90.63–110.08%), and 101.12% (99.17–103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC_0–t, C_max, and AUC_0–∞ were 103.00% (100.94–105.11%), 101.90% (99.63–104.22%), and 102.99% (100.87–105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (C_max, AUC_0–72, and AUC_0–∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00–125.00% for both the fasting and fed states. Both treatments have comparable safety profiles.

Conclusion

The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated am