Asthma
Conditions
Keywords
Asthma, HFA-152a, HFA-134a, pMDI
Brief summary
The purpose of the study is to assess the propellants,1 - Difluoroethane \[HFA-152a\] (Test) and 1,1,1,2-Tetrafluoroethane \[HFA-134a\] (Reference) for their potential to cause the airways to tighten when delivered through pressurized metered dose inhalers (pMDI). The rationale for this study is to develop a low carbon footprint alternative propellant, HFA-152a, which will have a lower impact on global warming.
Interventions
DRUGHFA-152A propellant
HFA-152A propellant is administered via oral inhalation
DRUGHFA-134A propellant
HFA-134A propellant is administered via oral inhalation
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
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Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Participants are eligible to be included in the study if all the following criteria apply: * Male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal. * Participant must be 18 to 45 years of age inclusive, at the time of screening. * Confirmed diagnosis of asthma: documented, established diagnosis of asthma for at least 6 months. * Receiving 1 of the 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: * As needed short-acting beta-agonists (SABA) only * As needed SABA plus low-dose Inhaled corticosteroids (ICS) (defined as 100-250 µg/day fluticasone propionate or equivalent taken whenever SABA is taken). * Daily maintenance low-dose ICS, plus as needed SABA or ICS-SABA single inhaler combination therapy * Low dose combination single inhaler ICS-formoterol or single inhaler ICS-SABA as needed for symptom relief (and if needed, before exercise) * Leukotriene receptor antagonist (LTRAs) in combination with any of the above therapies * Asthma Control Questionnaire (ACQ)-6 score \<1.5 at screening and Day -1. * No severe asthma exacerbations within 6 months prior to screening and ≤1 severe exacerbation during the 12 months prior to screening. * Lung function: subjects with a pre-bronchodilator FEV1 ≥60% predicted at Screening and Day-1. * A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a Woman of non-childbearing potential (WONCBP) OR * Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1%. * Female participants must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 28 days before the first dose of study intervention. * For male participants, no contraceptive measures are required. * Non-smokers, or previous smokers who have not used any tobacco containing-products or vaping products within 12 months prior to study start, and with a total pack year history of ≤10 pack years. * The use of marijuana, even with a valid prescription, is prohibited within 12 months prior to study start. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and protocol.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator. * Asthma treatment requiring use of biologic agents (e.g. mepolizumab or dupilumab), chronic systemic corticosteroids, or oral controller agents other than LTRAs. * 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, tuberculosis and other respiratory abnormalities other than asthma 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 and/or requires additional therapy during the study. This includes history of lung cancer and previous thoracic surgery such as lung resection. * Asthma Exacerbation: Any severe asthma exacerbation within 6 months prior to screening. (Severe asthma exacerbation defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days, or a single depo injection or an in-patient hospitalization or early discontinuation (ED) visit due to asthma that required systemic corticosteroids). * Biologic/immunosuppressive therapies that can be used for the treatment of respiratory diseases during the 6 months, or 5 half-lives whichever is longer-prior to start of the study. * Participants undergoing de-sensitization therapy. * Administration of systemic, oral, or depot corticosteroids for asthma treatment within 12 weeks of Visit 1. Intranasal corticosteroids are permitted if at a stable dose for at least 3 months prior to screening. * Stable doses (3 months or longer) of the following are permitted: * Intranasal corticosteroids * Oral anti-histamines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at 15 Minutes Post-dose | Baseline (Day 1, pre-dose) and at 15 minutes post-dose | FEV1 is defined as the volume of air that can be forced out in one second, after taking a deep breath and measured using spirometry. Baseline is defined as the latest pre-dose assessment with a non-missing value including those from unscheduled visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve for FEV1 From Time Zero to 15 Minutes (FEV1 AUC0-15 Mins) | Up to 15 minutes post-dose | FEV1 was measured using spirometry. AUC was assessed from the first non-missing timepoint to the 15 minute time point. |
| Percentage Change From Baseline in FEV1 at 5, 60, and 180 Minutes Post-dose | Baseline (Day 1, pre-dose) and at 5, 60, and 180 minutes post-dose | FEV1 is defined as the volume of air that can be forced out in one second, after taking a deep breath and measured using spirometry. Baseline is defined as the latest pre-dose assessment with a non-missing value including those from unscheduled visits. |
| Number of Participants With Percentage Change From Baseline in FEV1 <-15% at Timepoints 5, 15, 60 and 180 Minutes Post-dose | Baseline (Day 1, pre-dose) and at 5, 15, 60 and 180 minutes post-dose | FEV1 is defined as the volume of air that can be forced out in one second, after taking a deep breath and using spirometry. Baseline is defined as the latest pre-dose assessment with a non-missing value including those from unscheduled visits. |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Up to approximately 85 days | An AE is defined as any untoward medical occurrence in a clinical study participant that was temporally associated with the use of a study intervention, regardless of whether it was related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability or incapacity, or was a congenital anomaly, birth defect, or abnormal pregnancy outcome. SAEs are a subset of AEs. AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) coding system. |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 36.0 years STANDARD_DEVIATION 8.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 1 / 20 | 1 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
None listed