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Safety, Tolerance and Pharmacokinetics of HFA-152a in Healthy Volunteers

Kuehl PJ, Corr S, Leach CL.

Respiratory Drug Delivery 2022. Volume , 2022: 87-96.

Abstract:

HFA-152a (1, 1-difluoroethane) is being developed as an alternative propellant in pressurized metered dose inhalers (pMDIs). A comprehensive HFA-152a development program is being conducted to support a drug master file suitable for global regulatory submissions. A global regulatory strategy was developed to include analytical assay development, aerosol development, bioanalytical assay development, respiratory sensitization, toxicology (multiple species, acute, sub-chronic, chronic, reproductive and carcinogenicity) to support a US Investigational New Drug (IND) approval to conduct a Phase I propellant-only clinical study.

The Phase I human study was conducted in healthy male volunteers. The volunteers were administered four consecutive doses of 50 μL/actuation from a pMDI within a six-minute timespan which represented the maximum anticipated single dosing session currently utilized in pMDI treatment. Immediately following the last actuation, blood samples were collected for gas chromatography (GC)-headspace analysis for HFA-152a to support pharmacokinetic studies. Additionally, quantitative end points for safety and tolerance were conducted to include pulmonary function testing (PFT), vital signs, taste, clinical chemistry, and clinical observations.

Overall, the data showed that following oral inhalation from a pMDI, HFA-152a was well tolerated, had minimal impact on main aspects of taste scoring and was rapidly cleared from the blood. There were no adverse events during the study. These data support the continued development and utilization of HFA-152a as a safe alternative propellant for use in pMDIs.