28-DAY DOUBLE-BLIND SAFETY STUDY OF AN HFA-134A INHALATION AEROSOL SYSTEM IN HEALTHY-SUBJECTS

A 28-day double-blind parallel group study has been conducted to compa re the safety and tolerability of HFA-134a, a chlorofluorocarbon-free propellant in a pressurized metered-dose inhaler (MDI A), with a chlor ofluorocarbon propellant (MDI C). Sixteen subjects were randomly assig ned to receive one of the two MDIs, either four inhalations four times per day for 14 days or eight inhalations four times a day for 14 days , and were then crossed over to the alternative exposure regime with t he same propellant for the next 14 day period. No clinically significa nt changes occurred in blood pressure, heart rate, electrocardiograms, pulmonary function (FEV(1), FVC, FEF(25-75%)), haematology or serum c hemistry. One subject in the MDI A group had elevated eosinophil count s throughout the study; there were no other remarkable clinical labora tory data. Fifty six adverse events were related to the study propella nts; 34 of these occurred in the MDI C group and 22 in the MDI A group . For each adverse event no statistically significant differences were detected between propellant systems or between exposure levels. The m ost frequent adverse event was headache, which was reported by four su bjects with each propellant system. Blood samples for HFA-134a in the MDI A group were collected on day 28 to measure systemic absorption. B lood levels of HFA-134a were detected in all subjects given this prope llant within 1 min post-exposure, and these levels decreased to one-te nth of the original value by 18 min after the start of exposure. The s afety and tolerability of an HFA-134a chlorofluorocarbon-free system w as demonstrated over 28 days of exposure in healthy subjects. These ne gative results are clinically important because they indicate it will be safe to proceed with the study of this chlorofluorocarbon-free syst em in asthmatic patients.