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 and older with asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

1 Jul 2024 → 2 Sep 2025

Decision date (initial)

2024-06-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pharma R&D

External identifiers

EU CT number

2023-509001-76-00

ClinicalTrials.gov

NCT06261957

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Assess the safety and tolerability of 3 months treatment with a formulation of salbutamol administered via MDI containing propellant test HFA- 152a or reference HFA-134a in participants 18 years of age and older with asthma

Secondary objectives 2

1. To assess the safety and tolerability of salbutamol test (HFA-152a MDI) or reference (HFA-134a MDI) in participants ≥18 years of age with asthma.
2. To assess ACQ-6 score and FEV1 in salbutamol test (HFA-152a MDI) or reference (HFA-134a MDI) in participants ≥18 years of age with asthma.

Conditions and MedDRA coding

Asthma

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

Yes

IPD plan description

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant must be 18 years of age or older 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 GINA [GINA, 2023]. Receiving one of the following asthma treatments, at a stable dose (applicable to daily ICS, ICS/LABA, and ICS/LABA/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: o SABA used as needed for asthma symptoms o Daily maintenance low to medium dose 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 SABA, which is anticipated to remain stable for the duration of the study. o Daily maintenance low to medium dose ICS/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. o 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. o Subjects who utilize combination budesonide/formoterol as reliever therapy, whether or not this is in addition to a SABA – are not eligible for screening. o Subjects 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: • Baseline pre-bronchodilator FEV1 ≥60% of predicted at screening. o Participants who are unable to perform the pre-bronchodilator FEV1 maneuvers at Visit 1 can, at the discretion of the investigator, attend the clinic once more after Visit 1 to attempt to perform the pre-bronchodilator FEV1 maneuvers again, as well as perform the post-bronchodilator FEV1 maneuvers for the assessment of reversibility (see Inclusion Criterion 5). This must be within the screening period. o Should the participant successfully meet the requirements of Inclusion Criterion 3 at the second attempt then, provided that Inclusion Criterion 5 is met and all eligibility criteria assessed at Visit 1 are met, the participant may enter the run-in period. o Should the participant not successfully meet the requirements of Inclusion Criterion 3 at the second attempt then they will not be considered eligible for further study participation.
4. Asthma Control Status • 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: o Deterioration of asthma-requiring the use of systemic corticosteroids (tablets, suspension or injection), for at least 3 days, OR o An inpatient hospitalization or ED visit because of asthma, requiring systemic corticosteroids.
5. Evidence of reversibility of disease: Airway reversibility is defined as ≥12% and ≥200 mL increase in FEV1 within 20 to 60 minutes following up to 4 inhalations of albuterol/salbutamol aerosol. Subjects 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. o SABA should be withheld for ≥6 hours o If the subject does not meet the above reversibility definition at Visit 1 then the reversibility assessment may be repeated once during the screening period. o Subjects who fail 2 attempts at reversibility testing cannot make another attempt but may be rescreened. Subjects 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. o SABA should be withheld for ≥6 hours o LABA- and LAMA-containing medications should be withheld for ≥24 hours for the characterization of post-bronchodilator change.
6. Subjects should be able to withhold SABA for ≥6 hours and LABA-containing medications for ≥24 hours for the purposes of performing spirometry.

Exclusion criteria 8

1. A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator. NOTE: Life-threatening asthma is defined as an asthma episode that required intubation/non-invasive positive pressure ventilation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
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. Participants must have had no more than 1 severe exacerbation during the 12 months prior to screening.
6. Other concurrent diseases/abnormalities: A participant has any clinically significant or uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the participant at risk through study participation or would confound the interpretation of the study results if the condition/disease exacerbated during the study. (e.g., stroke or MI within 3 months, uncontrolled hypertension, congestive heart failure).
7. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of AEs throughout the 3 months treatment period

Secondary endpoints 12

1. Incidence of SAEs
2. Minimum serum potassium
3. Absolute values for serum potassium at each assessed visit
4. Change from baseline for serum potassium at each assessed visit.
5. Absolute values for clinical laboratory assessments at each assessed visit.
6. Change from baseline for clinical laboratory assessments at each assessed visit
7. Absolute values for vital signs parameters (systolic blood pressure, diastolic blood pressure, pulse rate) at each assessed visit
8. Change from baseline for vital signs parameters (systolic blood pressure, diastolic blood pressure, pulse rate) at each assessed visit.
9. Absolute values for 12 Lead ECGs in QTc and heart rate at each assessed visit
10. Change from baseline for 12 Lead ECGs in QTc and heart rate at each assessed visit.
11. Change from baseline for ACQ-6 score at each assessed visit.
12. Change from baseline for pre-bronchodilator FEV1 at each assessed visit

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 13

Locations

5 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 71 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications