Clinical trial NCT06433908: A Study to Compare the Pharmacokinetics (PK) of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152A (Test) or HFA-134A (Reference) in Healthy Participants Aged 18 to 55 Inclusive
Official title: A Phase 1, Randomized, Open-label, Single Dose, 2-treatment Arm (200 μg and 800 μg), 4-way Crossover Study in Healthy Participants Aged 18 to 55 to Compare the Pharmacokinetics of Salbutamol Administered Via Metered Dose Inhalers Containing Propellants HFA-152A (Test) and HFA-134A (Reference)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Healthy Participants
Keywords: salbutamol
propellant HFA-152a
propellant HFA-134a
metered dose inhalers
healthy participants
asthma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 4-way crossover study.
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to characterize the PK of single doses of salbutamol in healthy participants delivered via an MDI containing propellant HFA-152a (test), and to compare with an MDI containing propellant HFA-134a (reference).


Eligibility criteria: Inclusion Criteria:

1. Sex: male or female; females may be of childbearing potential, of nonchild bearing potential, or postmenopausal.
2. Age: 18 to 55 years inclusive.
3. Weight: 45 to 110 kg inclusive
4. Status: healthy participants.
5. Females must not be pregnant or lactating.
6. All prescribed medication must have been stopped at least 30 days prior to admission to the clinical research center based on investigator judgment. An exception is made for hormonal contraceptives, which may be used throughout the study.
7. All over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g., St. John's wort) must have been stopped at least 14 days prior to admission to the clinical research center based on investigator judgment. An exception is made for acetaminophen, which is allowed up to admission to the clinical research center.
8. Ability and willingness to abstain from alcohol from 48 hours (2 days) prior to screening, and from 48 hours (2 days) prior to admission until discharge from the clinical research center.
9. Ability and willingness to abstain from methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks) from 48 hours (2 days) prior to admission until discharge from the clinical research center.
10. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs, as judged by the investigator.
11. Serum potassium and serum glucose levels within reference ranges of the clinical research center.
12. Willing and able to sign the informed consent form.
13. Spirometry at screening demonstrating forced expiratory volume ≥80% predicted.

Exclusion Criteria:

1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs.
2. History or presence of any form of asthma, including childhood asthma and exercise induced asthma.
3. At screening, systolic blood pressure \<90 mmHg or \>140 mmHg, or diastolic blood pressure \<50 mmHg or \>90 mmHg.
4. History of pathological tachycardia, or a pulse rate \> 85 beats per minute (bpm) at screening or Day-1.
5. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
6. Breast cancer within the past 10 years.
7. A QTcF value of \>450 msec at screening based on a triplicate measurement taken at a single timepoint.
8. Vaccine(s) within 2 weeks prior to admission, or plans to receive such vaccines during the study.
9. Donation or loss of more than 450 mL of blood within 60 days prior to (the first) drug administration. Donation or loss of more than 1.5 L of blood (for male participants) or more than 1.0 L of blood (for female participants) in the 10 months prior to (the first) drug administration in the current study.
10. Participation in a drug study within 30 days prior to (the first) drug administration in the current study. Participation in 4 or more other drug studies in the 12 months prior to (the first) drug administration in the current study.
11. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
12. Presence of hepatitis B surface antigen at screening or within 3 months prior to first dose of study intervention.
13. Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention. NOTE: Participants with positive hepatitis C antibody test result due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C RNA test is obtained.
14. Positive pre-study drug/alcohol screen, including tetrahydrocannabinol.
15. Positive HIV antibody test.
16. Cotinine levels indicative of smoking or history or use of tobacco- or nicotine containing products within 6 months prior to screening.

    Assessment as ineligible by the investigator based on the results of the clinical laboratory tests or other assessments.
17. Average intake of more than 24 units of alcohol per week: 1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits.
18. Regular use of known drugs of abuse, including tetrahydrocannabinol.
19. Use of combustible tobacco products, and non-combustible nicotine delivery systems, inclusive of cigarettes, cigars, pipes, and materials used to "vape" within 6 months prior to screening.
20. Use of any products intended to treat medical conditions that are not approved by the governing health authority in a given country or region (for example, herbal medicine, health supplements, traditional medicine, homeopathic remedies, etc.).
21. Impairment which would prevent the correct and consistent use of an MDI, as determined by the investigator/delegate.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC[0-30min])
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, and 30 minutes post-dose
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC[0-∞])
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
Secondary outcomes:
measure: Time to Reach Cmax (Tmax)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Apparent Terminal Phase Half-life (t1/2)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Area Under the Plasma Concentration-time Curve up to Last Time with Concentrations Above the Lower Limit of Quantification (LLOQ) (AUC[0-last])
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Intra-participant Variability of AUC(0-30min)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, and 30 minutes post-dose
measure: Intra-participant Variability of AUC(0-∞)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Intra-participant Variability of AUC(0-last)
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Intra-participant Variability of Cmax
timeFrame: On each dosing day (Day 1, 4, 7, and 10) PK blood samples will be taken at pre-dose, at 3, 5, 10, 15, 20, 30, and 45 minutes post-dose; and at 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 18
measure: Absolute Values for 12 Lead Electrocardiogram (ECGs) Recording of Heart Rate (HR)
timeFrame: At screening (Day -28 to -1), admission (Day -1), on each dosing day (Day 1, 4, 7, and 10) at pre-dose and at 30 minutes post-dose and at discharge (Day 11)
measure: Absolute Values for 12 Lead ECGs Recording of QTc Intervals
timeFrame: At screening (Day -28 to -1), admission (Day -1), on each dosing day (Day 1, 4, 7, and 10) at pre-dose and at 30 minutes post-dose and at discharge (Day 11)
measure: Change from Baseline for Post-dose 12 Lead ECGs Recording of HR
timeFrame: Baseline and on each dosing day (Day 1, 4, 7, and 10) at pre-dose and at 30 minutes post-dose and at discharge (Day 11)
measure: Change from Baseline for Post-dose 12 Lead ECGs Recording of QTc Intervals
timeFrame: Baseline and on each dosing day (Day 1, 4, 7 and, 10) at pre-dose and at 30 minutes post-dose and at discharge (Day 11)
measure: Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters
timeFrame: Day-1 (admission) up to discharge (Day 11)
measure: Absolute Values of Vital Signs (Systolic and Diastolic Blood Pressure)
timeFrame: At screening (Day -28 to -1), admission (Day -1), on each dosing day (Day 1, 4, 7, and 10) at pre-dose and at the following time points post-dose: 15, 30 minutes, 1, 2, 4 hours, and at discharge (Day 11)
measure: Absolute Values of Vital Signs (Pulse Rate)
timeFrame: At screening (Day -28 to -1), admission (Day -1), on each dosing day (Day 1, 4, 7, and 10) at pre-dose and at the following time points post-dose: 15, 30 minutes, 1, 2, 4 hours, and at discharge (Day 11)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: GSK Investigational Site
Study officials:
References: