Dose-Ranging and Cumulative Dose Studies of Albuterol Sulfate MDI in Co-Suspension Delivery™ Technology (AS MDI; PT007) in Patients with Asthma: the ASPEN and ANTORA Trials

Abstract

Background and Objectives Co-suspension Delivery™ Technology has been developed for the administration of albuterol sulfate pressurised inhalation suspension via metered-dose inhaler (AS MDI, PT007). We assessed the efficacy and safety of AS MDI versus Proventil ® in order to determine the optimal dose of AS MDI to take to Phase III clinical trials. Methods ASPEN (NCT03371459) and ANTORA (NCT03364608) were Phase II, randomised, crossover, multicentre studies of AS MDI versus Proventil ® in patients with persistent asthma. In ASPEN, 46 patients received cumulative-dose treatments (90 μg/inhalation using 1 + 1 + 2 + 4 + 8 inhalations at 30-minute intervals) in 1 of 2 possible sequences: AS MDI/Proventil or Proventil/AS MDI. In ANTORA, 86 patients were randomised to one of 10 treatment sequences of AS MDI (90 μg or 180 μg), placebo MDI, or Proventil (90 μg or 180 μg). The primary endpoints were baseline-adjusted forced expiratory volume in 1 second (FEV 1 ) 30 minutes after each cumulative dose (ASPEN) and change from baseline in FEV 1 area under the curve from 0 to 6 h (ANTORA). Safety was assessed in both studies. Results In ASPEN, AS MDI was equivalent to Proventil (within pre-specified bounds of ± 200 mL) following cumulative doses of albuterol up to 1440 μg for the primary endpoint. In ANTORA, 90 μg and 180 μg doses of AS MDI and Proventil were significantly superior to placebo MDI (p < 0.0001), and AS MDI was non-inferior to Proventil at both doses, based on a margin of 100 mL. No new safety concerns were identified. ConclusionThe effects of albuterol delivered via AS MDI and Proventil on bronchodilation were equivalent, supporting the selection of AS MDI 180 µg to be taken into Phase III clinical trials, either alone or in combination with an inhaled corticosteroid. Trial Registration number ASPEN (NCT03371459); Date of registration: 29/12/2017. ANTORA (NCT03364608); Date of registration: 15/12/2017.

Efficacy and safety of as-needed albuterol/budesonide versus albuterol in adults and children aged ≥4 years with moderate-to-severe asthma: rationale and design of the randomised, double-blind, active-controlled MANDALA study

“…The 180 µg albuterol dose was confirmed in two clinical trials, ANTORA and ASPEN. 27 Dose ranging for budesonide was conducted in study PT008001 in patients with asthma (NCT02105012). The current study included budesonide doses separately investigated in the Single inhaler Maintenance And Reliever Therapy (SMART) trials (ie, 160 µg and 80 µg) in order to provide budesonide dose ranging information for as-needed albuterol/budesonide to reduce the risk of severe asthma exacerbations.…”