In Vitro Flow Rate Dependency of Delivered Dose and Fine Particle Dose of Salmeterol/Fluticasone Propionate Easyhaler and Seretide Diskus with Patient Flow Rates Collected in a Randomized Controlled Trial

Abstract

Background: The Easyhaler^® device-metered dry powder inhaler containing Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). We report two studies which evaluated the in vitro flow rate dependence of delivered dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide Diskus^®.

Methods: A randomized controlled trial (RCT) assessed inspiratory flow parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with asthma (children, adolescents and adults, and elderly) and in COPD patients. The 10th, 50th, and 90th percentile airflow rates were determined and utilized in vitro, to evaluate flow rate dependence of DD and FPD. Flow rate dependence was evaluated relative to the result obtained at the 50th percentile and any values deviating from 100% indicated flow rate dependence. The volumetric flow rate dependence (Q) index derived from FPD at 10th and 90th percentile airflows was also evaluated.

Results: Overall, 227 patients were enrolled and randomized; 216 completed the RCT. In total, 55.5% of patients were female, and the mean age was 46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into the in vitro study, which demonstrated similar flow rate dependence of DD and FPD for S/F Easyhaler compared with Seretide Diskus; all values were within ±15% limits across the 10th, 50th, and 90th percentile airflow rates. Q index results suggested that both S/F Easyhaler and Seretide Diskus are medium airflow-dependent products.

Conclusions: Similar in vitro flow rate dependence of DD and FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a range of clinically relevant airflow rates, collected from patients with asthma and COPD.

Keywords: Salmeterol/Fluticasone Easyhaler; delivered dose; fine particle dose; flow rate dependency.

FIG. 1.

Patient disposition. *Six exclusions occurred in the subgroup of children with asthma; three patients were excluded from the subgroup of adolescents and adults with asthma; and one patient was excluded from each of the other two subgroups. PP, per protocol.

FIG. 2.

PIF rates (L/min) through Salmeterol/Fluticasone propionate Easyhaler and Seretide Diskus by patient subgroup (PP population; n = 216). COPD, chronic obstructive pulmonary disease; PIF, peak inspiratory flow; SD, standard deviation.

FIG. 3.

Individual PIF rates in each patient subgroup for Salmeterol/Fluticasone propionate Easyhaler (A) and Seretide Diskus (B) (PP population; n = 216).

FIG. 4.

Relative in vitro dependency of Salmeterol and Fluticasone propionate DD at clinically relevant flow rates for Salmeterol/Fluticasone propionate Easyhaler and Seretide Diskus*. *10th, 50th, and 90th percentile airflow rates: 46, 68, and 85 L/min and 44, 71, and 96 L/min for Salmeterol/Fluticasone propionate Easyhaler and Seretide Diskus, respectively; ^†Salmeterol strength: 50 μg/dose in both products; ^‡Fluticasone propionate strength: 250 and 500 μg in the two respective products. DD, delivered dose.

FIG. 5.

Relative in vitro flow rate dependency of Salmeterol and Fluticasone propionate FPD at clinically relevant flow rates for Salmeterol/Fluticasone propionate Easyhaler and Seretide Diskus. 10th, 50th, and 90th percentile airflow rates: 46, 68, and 85 L/min and 44, 71, and 96 L/min for Salmeterol/Fluticasone propionate Easyhaler and Seretide Diskus, respectively; ^†Salmeterol strength: 50 μg/dose in both products; ^‡Fluticasone propionate strength: 250 and 500 μg in the two respective products. FPD, fine particle dose.