A Phase 1, Randomized, 2-part, 7-way Cross-over (Part 1) and 7-way Cross-over (Part 2), Blinded, Single Dose Study in Mild Asthmatics Aged 18-65 to Assess the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers Containing Propellants HFA-152a (Test) and HFA-134a (Reference) Via Methacholine Bronchoprovocation and Systemic Pharmacodynamic Effects
The primary objectives of the study are: Part 1: to characterize the potency and variability of dose response on efficacy (Provocative concentration of methacholine causing at least a 20% fall in forced expiratory volume (FEV1) \[PC20\]) of salbutamol administered via MDI with salbutamol HFA-134a or salbutamol HFA-152a in participants with mild asthma. Part 2: to compare the comparative dose response on efficacy (PC20) of salbutamol when administered via MDI with salbutamol HFA-134a or salbutamol HFA-152a in participants with mild asthma.
• Male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
• Participant must be 18 to 65 years of age inclusive, at the time of screening.
• ≥50 kg, at the time of screening.
• Body mass index (BMI) with 19.0-35.0 kg/m2 inclusive, at the time of screening.
⁃ 4\. Documented history of asthma ≥ 6 months. 5. Receiving 1 of following asthma treatments, at a stable dose, for at least 12 weeks prior to the screening visit and is anticipated to remain stable for the duration of the study: i. Short-acting beta-agonist (SABA) only. ii. Daily maintenance low-dose inhaled corticosteroids (ICS) (defined as 100-250 μg/day fluticasone propionate or equivalent plus or minus SABA which is anticipated to remain stable for the duration of the study.
⁃ iii. Daily maintenance low-dose ICS + Long-acting beta-2 agonist (LABA) therapy (low-dose ICS defined as 100-250 μg/day fluticasone propionate or equivalent as defined by GINA \[GINA, 2023\]) plus or minus SABA, which is anticipated to remain stable for the duration of the study.
⁃ 6\. No severe asthma exacerbations within 6 months prior to screening and ≤1 severe exacerbation during the 12 months prior to screening.
⁃ 7\. Pre-bronchodilator FEV1 ≥80% of predicted, at screening. 8. PC20 to methacholine of ≤8 mg/mL, at screening. 9. Participants should be able to withhold SABA for ≥8 hours and LABA-containing medications for ≥48 hours for the purposes of performing the spirometry and methacholine challenge at screening and during the study visits (treatment periods).
⁃ 10\. A female participant is eligible to participate if she is not pregnant or breastfeeding, and Is a woman of woman of nonchildbearing potential (WONCBP) OR ii. Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective.
⁃ 11\. Provide signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
⁃ 12\. Non-smokers who have not used any tobacco containing-products within 12 months prior to study start, and with a total pack year history of ≤10 pack years.