A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive

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.

Study Overview

• Status: Recruiting
• Conditions: Asthma; Mild Asthma
• Intervention / Treatment: Drug: Salbutamol HFA-152a; Drug: Salbutamol HFA-134a; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9QZ
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Dave S Singh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Part 1 will consist of a 7 treatment, 7 period cross-over evaluation with all participants receiving the following treatments once, randomized to varying pre-specified sequences of: Zero dose (placebo of both salbutamol HFA-134a and salbutamol HFA-152a); 100 μg salbutamol HFA-134a; 200 μg salbutamol HFA-134a; 400 μg salbutamol HFA-134a; 100 μg salbutamol HFA-152a; 200 μg salbutamol HFA-152a; 400 μg salbutamol HFA-152a A minimum of a 2-day and maximum of a 7-day methacholine washout will separate each treatment period.	Drug: Salbutamol HFA-152a; A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.; Drug: Salbutamol HFA-134a; A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.; Drug: Placebo; A single placebo HFA-152a suspension or placebo HFA-134a suspension dose, given as at 20 second intervals.
Experimental: Part 2; Part 2 will consist of a 7 treatment, 7-way cross-over with all participants receiving the following treatments given once, randomized to varying pre-specified sequences of: Zero dose (placebo of both salbutamol HFA-134a and salbutamol HFA-152a); 100 μg salbutamol HFA-134a; 200 μg salbutamol HFA-134a; 400 μg salbutamol HFA-134a; 100 μg salbutamol HFA-152a; 200 μg salbutamol HFA-152a; 400 μg salbutamol HFA-152a A minimum of a 2-day and maximum of a 7-day methacholine washout will separate each treatment period.	Drug: Salbutamol HFA-152a; A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.; Drug: Salbutamol HFA-134a; A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.; Drug: Placebo; A single placebo HFA-152a suspension or placebo HFA-134a suspension dose, given as at 20 second intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Provocative concentration of methacholine causing at least a 20% fall in FEV1 (PC20)	Up to 11 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak QTc Interval		Up to 11 weeks
Peak Heart Rate (HR)		Up to 11 weeks
Minimum Serum Potassium		Up to 11 weeks
Maximum Observed Plasma Concentration (Cmax)		Up to 11 weeks
Time to Reach Cmax (Tmax)		Up to 11 weeks
Area Under the Plasma Concentration-time Curve up to Last Time With Concentrations Above the Lower Limit of Quantification (LLOQ) (AUC[0-last])		Up to 11 weeks
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to 11 weeks
Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR		Up to 11 weeks
Change from Baseline for Post-dose 12-lead ECGs Recording of HR	The 3 predose measures will be recorded and will be averaged for HR to derive 1 baseline value.	Baseline and up to 11 weeks
Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters		Up to 11 weeks
Absolute Values of Vital Signs (Systolic and Diastolic Blood Pressure)		Up to 11 weeks
Absolute Values of Vital Signs (Pulse Rate)		Up to 11 weeks
Absolute Values for 12-lead ECGs Recording of Intervals	Intervals recorded: - PR. - QRS. - QT. - QTc	Up to 11 weeks
Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals	The 3 predose measures will be recorded and will be averaged for QTc interval to derive 1 baseline value. Intervals recorded: - PR. - QRS. - QT. - QTc	Up to 11 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): November 6, 2026

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: May 23, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Mild asthma; Salbutamol; Propellant HFA-152a; Propellant HFA-134a; Metered dose inhalers
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Reproductive Control Agents; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Norflurane
• Other Study ID Numbers: 219729; 2024-511220-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No