Clinical trial NCT06261957: A Study to Assess and Compare Safety and Tolerability of 3 Months Treatment With Salbutamol Administered Via MDI Containing Propellant HFA-152a or HFA-134a in Participants ≥ 18 Years of Age With Asthma
Official title: A Randomized, Double-blind, Parallel Group, Multi-center Study to Evaluate the Long-term Safety of Salbutamol Rescue Medication When Administered Via Metered Dose Inhalers Containing the Propellant HFA-152a or Reference HFA-134a
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Salbutamol
MDI
HFA-152a
HFA-134a
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-02-15
Enrollment: 412
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to assess and compare the safety and tolerability of salbutamol administered via metered dose inhaler (MDI) containing propellant 1,1-difluoroethane (HFA-152a) or 1,1,1,2-tetrafluoroethane (HFA-134a) in participants aged \>=18 years with asthma


Eligibility criteria: Inclusion Criteria:

1. Participant of ≥18 years of age at the time of signing the informed consent or written informed consent is obtained from each study participant's legal guardian.
2. Asthma for ≥ 6 months, defined as:

   * Documented history of asthma, as defined by Global Initiative for Asthma (GINA) (GINA, 2023\]
   * Receiving one of the following asthma treatments, at a stable dose (applicable to daily Inhaled corticosteroid (ICS), ICS/Long-acting bronchodilator (LABA), and ICS/LABA/Long-acting muscarinic antagonist \[LAMA\]), for at least 12 weeks prior to the screening visit, with treatment that is anticipated to remain stable for the duration of the study:

     * Short-Acting Beta-2-Adrenoreceptor Agonists (SABA) used as needed for asthma symptoms
     * Daily maintenance low to medium dose Inhaled corticosteroid (ICS) (low to medium dose ICS defined as 100-500 μg/day fluticasone propionate or equivalent as defined in the 2023 GINA guidelines \[GINA, 2023\], plus Short-Acting Beta-2-Adrenoreceptor Agonists (SABA), which is anticipated to remain stable for the duration of the study.
     * Daily maintenance low to medium dose ICS/ Long-acting bronchodilator (LABA) (low to medium dose ICS defined as 100-500 μg/day fluticasone propionate or equivalent as defined in the GINA guidelines \[GINA, 2023\] plus SABA, which is anticipated to remain stable for the duration of the study.
     * Daily maintenance ICS/LABA/LAMA (low to medium dose ICS defined as 100-500 µg/day fluticasone propionate or equivalent as defined in the GINA guidelines \[GINA, 2023\] plus SABA, which is anticipated to remain stable for the duration of the study.
     * Participants who utilize combination budesonide/formoterol as reliever therapy, whether or not this is in addition to a SABA - are not eligible for screening.
     * Participants who utilize ICS/SABA combination therapy as reliever therapy, in addition to low to medium dose ICS or ICS/LABA as maintenance, are only eligible if they agree to discontinue their ICS/SABA inhaler for the duration of the study (screening through follow-up).
3. Severity of disease assessed by the investigator by baseline pre-bronchodilator Forced expiratory volume in 1 second (FEV1)
4. Asthma Control Status

   * Asthma Control Questionnaire (ACQ) 6 score \<1.5 at screening
   * Asthma that has remained stable with no severe exacerbations in the last 6 months. Severe exacerbation defined as:

     * Deterioration of asthma-requiring the use of systemic corticosteroids (tablets, suspension or injection), for at least 3 days, OR
     * An inpatient hospitalization or Emergency Department (ED) visit because of asthma, requiring systemic corticosteroids.
5. Evidence of reversibility of disease: Airway reversibility is defined as ≥12 percent (%) and ≥200 milliliter (mL) increase in FEV1 within 20 to 60 minutes following up to 4 inhalations of albuterol/salbutamol aerosol.
6. Participants on as-needed SABA only, or daily maintenance ICS (plus as needed SABA):

   * With a documented history of reversibility (as defined above) within 2 years will meet this inclusion criterion. Pre- and post-bronchodilator measurements will still be collected at screening to characterize the degree of reversibility.
   * Who do not have a documented history of reversibility within the past 2 years will need to demonstrate reversibility during the screening period.

     * SABA should be withheld for ≥6 hours
     * Participants on daily maintenance ICS/LABA or ICS/LABA/LAMA:
7. Participants on daily maintenance ICS/LABA or ICS/LABA/LAMA:

   * Do not need to demonstrate reversibility in accordance with the above definition during the screening period. A reversibility maneuver will be performed to characterize the degree of post-bronchodilator change.

     * SABA should be withheld for ≥6 hours
     * LABA- and LAMA-containing medications should be withheld for \>=24 hours for the characterization of post-bronchodilator change.

Participants should be able to withhold SABA for ≥6 hours and LABA-/ LAMA containing medications for ≥24 hours for the purposes of performing screening spirometry.

Exclusion Criteria:

1. A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator.
2. Other significant pulmonary diseases to include (but not limited to): pneumothorax, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, tuberculosis or other respiratory abnormalities other than asthma.
3. Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of screening that led to a change in asthma management, OR in the opinion of the Investigator, is expected to affect the participant's asthma status, OR the participant's ability to participate in the study.
4. Asthma Exacerbation: Any severe asthma exacerbation within 6 months prior to screening.
5. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) Biologic/immunosuppressive therapies used for the treatment of respiratory diseases during the 6 months, or 5 half-lives-whichever is longer-prior to start of the study.

Primary outcomes:
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to 3 months
Secondary outcomes:
measure: Number of participants with Serious Adverse Events (SAEs)
timeFrame: Up to 3 months
measure: Absolute Values of Minimum serum potassium (milliequivalents per litre [mEq/L])
timeFrame: Up to 3 months
measure: Absolute values of serum potassium (milligrams per decilitre)
timeFrame: Up to 3 months
measure: Change from baseline in serum potassium (milligrams per decilitre)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Absolute value of haematology parameter: Platelet count (cells per microliter)
timeFrame: Up to 3 months
measure: Absolute value of haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)
timeFrame: Up to 3 months
measure: Absolute value of haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)
timeFrame: Up to 3 months
measure: Absolute value of haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)
timeFrame: Up to 3 months
measure: Absolute values of haematology parameter: Reticulocytes (Percentage of reticulocytes)
timeFrame: Up to 3 months
measure: Absolute values of haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)
timeFrame: Up to 3 months
measure: Absolute values of haematology parameter: haemoglobin (Hgb) (grams per decilitre)
timeFrame: Up to 3 months
measure: Absolute values of haematology parameter: haematocrit (Proportion of red blood cells in blood)
timeFrame: Up to 3 months
measure: Absolute values of Clinical Chemistry parameters: Glucose (non-fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per decilitre)
timeFrame: Up to 3 months
measure: Absolute values of Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase, Alanine aminotransferase/serum glutamic-pyruvic transaminase, Alkaline phosphatase, Creatine phosphokinase (International Units per litre)
timeFrame: Up to 3 months
measure: Absolute value of routine urinalysis: potential of hydrogen (pH)
timeFrame: Up to 3 months
measure: Number of participants with abnormal urinalysis dipstick results: glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase
timeFrame: Up to 3 months
measure: Change from baseline in haematology parameter: Platelet count (cells per microliter)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameter: Red Blood Cell Count (RBC) (million cells per microliter)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameter: Mean Corpuscle Volume (MCV) (Femtoliters)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameter: Mean Corpuscle haemoglobin (MCH) (Picograms)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameter: Reticulocytes (Percentage of reticulocytes)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameters: Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (giga cells per litre)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameter: haemoglobin (Hgb) (grams per decilitre)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in haematology parameters: haematocrit (Proportion of red blood cells in blood)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in Clinical Chemistry parameters: Glucose (non-fasting), Blood Urea Nitrogen (BUN), Creatinine, Sodium, Potassium, Calcium, Direct Bilirubin and Total Bilirubin (milligrams per decilitre)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in Aspartate aminotransferase/ serum glutamic-oxaloacetic transaminase,Alanine aminotransferase/serum glutamic-pyruvic transaminase, Alkaline phosphatase, Creatine phosphokinase (International Units per litre)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in routine urinalysis: pH
timeFrame: Baseline (Day 1) and up to 3 months
measure: Absolute values for vital signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [millimeters of mercury (mm Hg)]
timeFrame: Up to 3 months
measure: Absolute values for vital sign: pulse rate [beats per min (bpm)]
timeFrame: Up to 3 months
measure: Change from baseline in vital signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [millimeters of mercury (mm Hg)]
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in vital sign: pulse rate [beats per min (bpm)]
timeFrame: Baseline (Day 1) and up to 3 months
measure: Absolute values for 12 Lead Electrocardiograms (ECGs) in Corrected QT interval (QTc) (milliseconds)
timeFrame: Up to 3 months
measure: Absolute values for heart rate [beats per min (bpm)]
timeFrame: Up to 3 months
measure: Change from baseline for 12 Lead ECGs in QTc (milliseconds)
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline for heart rate [beats per min (bpm)]
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline in Asthma Control Questionnaire (ACQ-6) score
timeFrame: Baseline (Day 1) and up to 3 months
measure: Change from baseline for pre-bronchodilator Forced expiratory volume in 1 second (FEV1)
timeFrame: Baseline (Day 1) and up to 3 months
Other outcomes:
Locations:
city: North Hollywood
country: United States
facility: GSK Investigational Site
state: California
city: San Mateo
country: United States
facility: GSK Investigational Site
state: California
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Clearwater
country: United States
facility: GSK Investigational Site
state: Florida
city: DeLand
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Naples
country: United States
facility: GSK Investigational Site
state: Florida
city: Plantation
country: United States
facility: GSK Investigational Site
state: Florida
city: Winter Park
country: United States
facility: GSK Investigational Site
state: Florida
city: Rincon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Stonecrest
country: United States
facility: GSK Investigational Site
state: Georgia
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Owensboro
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Minnesota
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Olive Branch
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Jersey City
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Riverdale
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Brooklyn
country: United States
facility: GSK Investigational Site
state: New York
city: Asheville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dublin
country: United States
facility: GSK Investigational Site
state: Ohio
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: DuBois
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pottstown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rock Hill
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Tomball
country: United States
facility: GSK Investigational Site
state: Texas
city: Bellingham
country: United States
facility: GSK Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: La Plata
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Botany
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Coffs Harbour
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Kanwal
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Murdoch
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Amiens Cedex 1
country: France
facility: GSK Investigational Site
city: Argenteuil cedex
country: France
facility: GSK Investigational Site
city: Cannes
country: France
facility: GSK Investigational Site
city: CrEteil cedex
country: France
facility: GSK Investigational Site
city: Poitiers
country: France
facility: GSK Investigational Site
city: Pontoise
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Alexandroupolis
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Cagliari
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Foggia
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Torino
country: Italy
facility: GSK Investigational Site
city: Tradate VA
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Ciudad de Panama
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Iloilo City
country: Philippines
facility: GSK Investigational Site
city: Iloilo
country: Philippines
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Bielsko-Biala
country: Poland
facility: GSK Investigational Site
city: Chorzow
country: Poland
facility: GSK Investigational Site
city: Elblag
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Ostrowiec Swietokrzyski
country: Poland
facility: GSK Investigational Site
city: Plock
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: BenalmAdena
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Marbella
country: Spain
facility: GSK Investigational Site
city: Pozuelo De AlarcOn Madr
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Pathumthani
country: Thailand
facility: GSK Investigational Site
city: Bebington
country: United Kingdom
facility: GSK Investigational Site
city: Cambridgeshire
country: United Kingdom
facility: GSK Investigational Site
city: Corby
country: United Kingdom
facility: GSK Investigational Site
city: Greater Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Guisborough
country: United Kingdom
facility: GSK Investigational Site
city: Hounslow
country: United Kingdom
facility: GSK Investigational Site
city: Rhyl
country: United Kingdom
facility: GSK Investigational Site
city: Uttoxeter
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: