Comparison of Systemic Pharmacodynamic Effects of Two Combination Pressurised Metered Dose Inhalers that Deliver Salmeterol and Fluticasone Propionate

Abstract

AIM

The aim was to test the systemic pharmacodynamic effects of the salmeterol component of two pressurized metered dose inhalers that delivered a combination of salmeterol and fluticasone propionate (SM/FP).

METHODS

This was a six-way crossover study in 43 adult subjects, using a single blind design (subject blinded to product and clinical assessor blinded for all measurements). Each subject received single doses of 2, 6, and 12 inhalations from test and reference products that delivered SM/FP as 25/125 mcg per inhalation. Heart rate, QTcB, and plasma potassium and glucose were monitored over 6 hours.

RESULTS

Safety equivalence was shown by relative potency analysis for primary endpoints of maximum heart rate and maximum QTcB, since the 90% confidence intervals for both endpoints were within the acceptance limit of (0.67, 1.50). There were 6 secondary analyses for relative potency and equivalence was met for 5 of these endpoints. There were also 18 pairwise comparisons performed at each dose level. No statistical differences (95% confidence intervals included zero) among these pairwise comparisons were seen at the 2 inhalation dose (therapeutic dose) or the 6 inhalation dose. At the supratherapeutic dose of 12 inhalations, the test product was either comparable to or statistically less than that of the reference product for all comparisons. Overall, the results demonstrated comparable systemic safety. No differences were seen between the products in reported adverse events.

CONCLUSION

The safety equivalence of the systemic pharmacodynamic effects of the SM component of the test and reference SM/FP products was demonstrated.

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