Evaluation of Long-Term Safety of Salbutamol Sulfate via MDI with Propellants HFA-152a and HFA-134a in Adults with Asthma

The primary objective of this study is to assess the **safety** and **tolerability** of a 3-month treatment with a formulation of **salbutamol** administered via metered dose inhalers (MDI) containing either the test propellant HFA-152a or the reference propellant HFA-134a in participants aged 18 years and older with **asthma**. This evaluation is clinically relevant as it aims to ensure that the new formulation is safe for long-term use in managing asthma, a chronic respiratory condition that requires effective and safe rescue medications.

Secondary objectives include:

• Assessing the safety and tolerability of the salbutamol test (HFA-152a MDI) or reference (HFA-134a MDI) in participants aged 18 years and older with asthma.
• Evaluating the Asthma Control Questionnaire (ACQ-6) score and Forced Expiratory Volume in 1 second (FEV1) in participants using the salbutamol test (HFA-152a MDI) or reference (HFA-134a MDI).

The clinical trial involves a total of **233 participants** diagnosed with **asthma**. The study population includes both male and female subjects who are **18 years of age or older**. Participants were selected based on specific inclusion criteria, including a documented history of asthma for at least six months and stable asthma treatment for a minimum of 12 weeks prior to the screening visit. The trial does not specify any particular lifestyle considerations such as diet or physical activity. However, participants must be able to withhold short-acting beta-agonists (SABA) for at least six hours and long-acting beta-agonists (LABA) for 24 hours for spirometry purposes. The trial includes a vulnerable population, indicating that additional ethical considerations are in place to protect these participants. The study aims to assess the safety and tolerability of a salbutamol formulation administered via metered-dose inhaler (MDI) in this population.

The clinical trial is designed as a **randomized, double-blind, parallel group, multi-center study** to evaluate the long-term safety of **salbutamol** rescue medication administered via metered dose inhalers (MDIs) containing either the propellant HFA-152a or the reference HFA-134a. The primary objective is to assess the safety and tolerability of a 3-month treatment in participants aged 18 years and older with **asthma**. The trial is expected to commence recruitment on June 21, 2024, and conclude by April 23, 2025, with an estimated duration of participant involvement of approximately 3 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, documented history of asthma, and stable asthma control. The screening visit will also involve assessments like pre-bronchodilator FEV1 and reversibility testing. Following successful screening, participants will enter a run-in period before randomization. Throughout the study, follow-up visits will be conducted to monitor safety endpoints, including the incidence of adverse events (AEs) and serious adverse events (SAEs), as well as secondary endpoints like serum potassium levels, vital signs, and ECG parameters. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate any changes from baseline measurements.

Participants are expected to adhere to the study protocol, including withholding certain medications prior to spirometry assessments. Conditions that may lead to early termination from the study include failure to meet inclusion criteria during the screening period, inability to comply with study procedures, or the occurrence of significant adverse events that warrant discontinuation. The trial is structured to ensure rigorous monitoring and data collection to achieve its primary and secondary objectives, contributing valuable insights into the safety profile of salbutamol administered via different propellants in MDIs.

The clinical trial involves the administration of two formulations of **salbutamol sulfate** via metered dose inhalers (MDIs) to evaluate their long-term safety in participants with asthma. The first formulation, marketed under the name Ventolin 100 microgramos/inhalación suspensión para inhalación en envase a presión, is a **pressurised inhalation suspension**. This formulation utilizes the propellant HFA-134a and is manufactured by GlaxoSmithKline, S.A. The active substance, salbutamol sulfate, is of chemical origin. The maximum daily dose for this formulation is 800 micrograms, with a total maximum dose of 67 milligrams over a treatment period of up to 3 months. The route of administration is inhalation, and the product is delivered using a metered dose inhaler. Compliance with the dosing schedule is monitored throughout the study.

The second formulation, identified by the sponsor product code AH3365, is also a **pressurised inhalation suspension** containing salbutamol sulfate. This formulation employs the test propellant HFA-152a and is developed by GlaxoSmithKline Research & Development Limited. Similar to the reference product, the maximum daily dose is 800 micrograms, with a total maximum dose of 67 milligrams over a 3-month treatment period. The administration route is inhalation, facilitated by a metered dose inhaler. The device used in this test product differs from the commercial Ventolin Evohaler due to a new valve required for compatibility with the new propellant. Participant compliance with the dosing regimen is closely monitored to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed using a range of primary and secondary endpoints. The primary endpoint focuses on the incidence of adverse events (AEs) throughout the 3-month treatment period. Secondary endpoints include the incidence of serious adverse events (SAEs), as well as various clinical and laboratory parameters. These parameters encompass minimum serum potassium levels, absolute values, and changes from baseline for serum potassium at each assessed visit. Additionally, absolute values and changes from baseline for clinical laboratory assessments, vital signs parameters (systolic blood pressure, diastolic blood pressure, pulse rate), and 12 Lead ECGs in QTc and heart rate will be evaluated at each assessed visit. The trial will also measure changes from baseline for the Asthma Control Questionnaire (ACQ-6) score and pre-bronchodilator **FEV1** at each assessed visit.

The collection and analysis of these efficacy parameters will be conducted at specified timepoints throughout the study. These assessments will be performed using validated scales and laboratory tests to ensure accuracy and reliability. The trial is designed to provide comprehensive data on the safety and efficacy of salbutamol administered via metered dose inhalers containing different propellants, HFA-152a and HFA-134a, in participants with asthma. The study aims to gather detailed information on the impact of the treatment on both clinical outcomes and laboratory measures, contributing to a thorough evaluation of the treatment's efficacy.