Study of the Effect of HFA-152a and HFA-134a Propellants on Mucociliary Clearance in Healthy Participants

A Randomized, Double-blind, Single-site, Two-way Crossover Phase 1 Study to Assess the Effect of Repeated Doses of Test Propellant (HFA-152a) on Mucociliary Clearance as Compared to Reference Propellant (HFA-134a) in Healthy Male and Female Participants

The main goal of the study is to assess the effect of the administration of reference propellant [HFA-134a (1,1,1,2 - Tetrafluoroethane)] and test propellant [HFA-152a (1 - Difluoroethane)] in healthy adults on mucociliary clearance (MCC).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: HFA-152a; Other: HFA-134a; Other: Radiolabeled saline solution

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all following criteria apply:

• Male or Female, age 30 to 55 years
• Body Mass Index (BMI): 18.0 to 32.0 kg/m2, inclusive, at screening
• Weight: ≥50 kg
• Nonsmokers or ex-smokers for more than 6 months with a smoking history of <10 pack years
• Status: healthy participants

• Spirometry data.

  • Forced Expiratory Volume in 1 second (FEV1) ≥80% of predicted values.
  • FEV1: Forced vital capacity (FVC) ratio >70%.
• Females must be of nonchildbearing potential, and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during the study intervention period and at least 30 days after the last dose of study intervention.

• Male participants are eligible to participate if they agree to:

  • Refrain from donating sperm
  • Either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
  • Or must agree to use a male condom when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. The female partner should additionally use a highly effective contraceptive method with a failure rate of <1% per year.
• All prescribed medication must have been stopped at least 30 days prior to admission to the clinical research centre based on investigator judgment. An exception is made for Hormonal Replacement Therapy (HRT), and occasional paracetamol which may be used throughout the study.
• Capable of giving written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Capable of using inhaler device with no physical or other issues which would impair the participant's ability to successfully use a metered dose inhaler (MDI) inhaler as instructed in this study.
• Ability to comply with the protocol. Participants have capacity and no issues which would impair their ability to comply with all aspects of the protocol during the study

Exclusion Criteria:

Participants who meet any of the following exclusion criteria at screening will not be eligible to participate in the study:

• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker shall participate in the study.
• History or presence of any form of asthma, including childhood asthma and exercise induced asthma.
• Respiratory disorders other than asthma. 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 (COPD), tuberculosis, known alpha 1 antitrypsin deficiency and other respiratory abnormalities other than asthma that, in the opinion of the investigator, could put the participant at risk through study participation or could affect the study analyses and data interpretation.
• Recent history of mild conditions potentially affecting Mucociliary clearance (MCC) (viral infections, cough, cold, active hay fever etc.) in the last 14 days.
• Recent use of drugs for treating conditions potentially affecting MCC (viral infections, cough, cold, etc.) in the last 30 days.
• Vaccine(s) within 2 weeks prior to admission or plans to receive such vaccines during the study.
• Current enrolment or past participation in this clinical study.
• Positive human immunodeficiency virus (HIV) antibody test.
• Regular use of known drugs of abuse, including Tetrahydrocannabinol (THC).
• Average intake of more than 21 units of alcohol per week in males and 14 units per week in females (clinical site standard: unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits) based on breath alcohol test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HFA-152a followed by HFA-134a	Other: HFA-152a; HFA-152a is administered via oral inhalation; Other: HFA-134a; HFA-134a is administered via oral inhalation; Other: Radiolabeled saline solution; Radiolabeled saline solution is administered via oral inhalation
Experimental: HFA-134a followed by HFA-152a	Other: HFA-152a; HFA-152a is administered via oral inhalation; Other: HFA-134a; HFA-134a is administered via oral inhalation; Other: Radiolabeled saline solution; Radiolabeled saline solution is administered via oral inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Percent Radiolabeled Particle Retention-time Curve up to 4 Hours [AUC(0-4h)] After Nebulized 99mTechnetium (99mTc) Inhalation on Day 7	[AUC(0-4h)] was assessed for Mucociliary clearance (MCC) in participants following administration of nebulized 99mTc on Day 7. Gamma scintigraphy was utilized to conduct assessments.	At 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 minutes on Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Radiolabeled Particle Retention at 1 Hour After Nebulized 99mTechnetium (99mTc) Inhalation on Day 7	Gamma scintigraphy was utilized to conduct assessments.	1 hour after inhalation on Day 7
Percentage of Radiolabeled Particle Retention at 1.5 Hours After Nebulized 99mTechnetium (99mTc) Inhalation on Day 7	Gamma scintigraphy was utilized to conduct assessments.	1.5 hours after inhalation on Day 7
Percentage of Radiolabeled Particle Retention at 3 Hours After Nebulized 99mTechnetium (99mTc) Inhalation on Day 7	Gamma scintigraphy was utilized to conduct assessments.	3 hours after inhalation on Day 7
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)	An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose, results in death; was life threatening; required hospitalization or prolongation of existing hospitalization; resulted in disability/incapacity; was a congenital anomaly/birth defect, abnormal pregnancy outcomes. SAEs are subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. The AE data presented below is of frequency threshold - 0%.	Up to approximately 13 weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Actual): October 24, 2024
• Study Completion (Actual): October 24, 2024

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Crossover; MCC; HFA-134a; HFA-152a
• 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; Anesthetics; Central Nervous System Depressants; norflurane
• Other Study ID Numbers: 221781

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
• product manufactured in and exported from the U.S.: No