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

Asthma Clinical Trial

Official title:

A Phase 1, Randomized, 2-part, 7-way Cross-over (Part 1) and 7-way Cross-over (Part 2), Active Device 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06433921
• Other study ID #: 219729
• Secondary ID: 2024-511220-14-0
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 4, 2024
• Est. completion date: October 15, 2024

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 91
• Est. completion date: October 15, 2024
• Est. primary completion date: October 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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. 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. 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.

10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

11. 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.

Related Conditions & MeSH terms

• Asthma
• Mild Asthma

Intervention

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.
• 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.
• Placebo
A single placebo HFA-152a suspension or placebo HFA-134a suspension dose, given as at 20 second intervals.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PC20	PC of methacholine causing at least a 20% fall in FEV1.	Up to 11 weeks
Secondary	Peak QTc Interval		Up to 11 weeks
Secondary	Peak Heart Rate (HR)		Up to 11 weeks
Secondary	Minimum Serum Potassium		Up to 11 weeks
Secondary	Maximum Observed Plasma Concentration (Cmax)		Up to 11 weeks
Secondary	Time to Reach Cmax (Tmax)		Up to 11 weeks
Secondary	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
Secondary	Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to 11 weeks
Secondary	Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR		Up to 11 weeks
Secondary	Absolute Values for 12-lead ECGs Recording of Intervals	Intervals recorded: PR; QRS; QT; QTc	Up to 11 weeks
Secondary	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
Secondary	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	Baseline and up to 11 weeks
Secondary	Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters		Up to 11 weeks
Secondary	Absolute Values of Vital Signs (Systolic and Diastolic Blood Pressure)		Up to 11 weeks
Secondary	Absolute Values of Vital Signs (Pulse Rate)		Up to 11 weeks