Overview

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.

Eligibility

Inclusion Criteria:

1. Male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
2. Participant must be 18 to 65 years of age inclusive, at the time of screening.
3. ≥50 kg, at the time of screening.
4. Body mass index (BMI) with 19.0-35.0 kg/m2 inclusive, at the time of screening.
5. 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.

Exclusion Criteria:

1. Medical Conditions
   1. A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator.
   2. A history of respiratory diseases to include (but not limited to): pneumothorax, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, cystic fibrosis, bronchiectasis, interstitial lung disease, emphysema, chronic obstructive pulmonary disease, tuberculosis, or other respiratory abnormalities other than asthma.
   3. Asymptomatic gallstones.
   4. History or current evidence of hematologic, neurologic, psychiatric, or other diseases that, in the opinion of the investigator, would put the participant at risk through study participation, or would affect the study analyses if the disease exacerbates during the study.
   5. Recent eye surgery or any other condition in which raised intracranial pressure (caused by forceful exhalation) would be harmful.
   6. Current use of cholinesterase inhibitor medication e.g., to treat myasthenia gravis.
2. Exposure to more than 4 new chemical entities within 12 months prior to the first

   dosing day or participation in a clinical study within 30 days of study start, or 5 half-lives of study drug if that is longer.

3. Participants who are currently or in the last 15 days have worked nightshifts.
4. Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males or >14 units for females.
5. A positive test result for drugs of abuse (including tetrahydrocannabinol) at screening or Day -1.
6. Use of combustible tobacco products, and non-combustible nicotine delivery systems, inclusive of cigarettes, cigars, pipes, and materials used to "vape" within 12 months prior to the start of the study.