The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers

Abstract

Objective

Two studies (Study I and Study II) were conducted in healthy Chinese volunteers to confirm that there was no pharmacokinetic drug interaction between AZE and FLU in MP-AzeFlu. The secondary objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components.

Methods

Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William’s design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC_0-tlast, AUC_0-∞ and C_max were analyzed.

Results

The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC_0–tlast, AUC _0–∞ and C_max were 100.29% (94.31–106.66%), 100.76% (94.60–107.32%) and 93.14% (81.47–106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC_0–tlast, AUC _0–∞ and C_max were 83.48% (69.81–99.82%), 100.19% (87.34–114.94%) and 81.91% (68.50–97.95%).

Conclusion

The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects.

Keywords:

• MP-AzeFlu
• azelastine
• fluticasone
• allergic rhinitis
• pharmacokinetics

Data Sharing Statement

Raw data were generated at Viatris. Derived data supporting the findings of this study are available from the corresponding author K.L. on request.

Acknowledgments

The authors acknowledge Arghya Bhattacharya, Ph.D., and Aswin Kumar A, MBBS, for medical writing support (Viatris).

Disclosure

JCG, ML, TY, DTN and RKR are employees of Viatris. All other authors have no declaration for this manuscript.

Additional information

Funding

The present study was funded by MEDA Pharma GmbH & Co. KG (a Mylan Company) now Viatris. The study sponsor was not involved in the study design; the collection, analysis, and interpretation of data; the writing of the manuscript; and the decision to submit the manuscript for publication.