Green (Sustainable) VENTOLIN - Pharmacokinetics (PK) Study in Healthy Participants

A Single Dose Two-way Cross-over Study in Healthy Participants to Compare the Pharmacokinetics (PK) of Salbutamol Administered Via Metered Dose Inhalers Containing Propellants HFA-152a and HFA-134a

This study will be conducted to compare the PK of salbutamol administered via metered dose inhalers (MDI) containing propellants 1,1-difluroethane (HFA-152a) and 1,1,1,2-tetrafluoroethane (HFA-134a) in healthy participants.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Salbutamol HFA-152a; Drug: Salbutamol HFA-134a

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18 to 55 years, inclusive, at screening
• Body mass index 18.0 to 30.0 kilograms per meter square (kg/m^2), inclusive, at screening
• Weight: greater than or equal to (>=)50 kg
• At screening, females must not be pregnant or lactating, or of non-childbearing potential
• Female participants of childbearing potential who have a fertile male sexual partner must agree to use adequate contraception
• Male participants, if not surgically sterilized, must agree to use adequate contraception
• Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, electrocardiogram, and vital signs, as judged by the investigator
• Willing and able to sign the informed consent form

Exclusion Criteria:

• 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; constituting a risk when taking the study intervention or interfering with the interpretation of data
• History or presence of any form of asthma, including childhood asthma and exercise induced asthma
• Current enrollment or past participation in this clinical study
• Participants with clinically significant abnormalities
• A positive pre-study drug/alcohol screen or a history (or suspected history) of alcohol misuse or substance abuse
• Positive nasopharyngeal polymerase chain reaction test for severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) on Day -1 or any known close contact with a person who tested positive for SARS-CoV-2 or with a coronavirus disease 2019 participant within 2 weeks prior to admission
• Impairment which would prevent the correct and consistent use of an MDI, as determined by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Salbutamol HFA-152a MDI followed by Salbutamol HFA-134a MDI; Participants will receive Salbutamol HFA-152a MDI in treatment period 1 followed by Salbutamol HFA-134a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.	Drug: Salbutamol HFA-152a; Salbutamol HFA-152a will be administered.; Drug: Salbutamol HFA-134a; Salbutamol HFA-134a will be administered.
Experimental: Salbutamol HFA-134a MDI followed by Salbutamol HFA-152a MDI; Participants will receive Salbutamol HFA-134a MDI in treatment period 1 followed by Salbutamol HFA-152a MDI in treatment period 2. There will be a minimum washout period of 72 hours between each treatment period.	Drug: Salbutamol HFA-152a; Salbutamol HFA-152a will be administered.; Drug: Salbutamol HFA-134a; Salbutamol HFA-134a will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC (0-30 Min)) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 3, 5, 10, 15, 20 and 30 minutes on Day 1 and Day 4
AUC From Time 0 to Infinity (AUC[0-inf]) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
AUC From Time 0 to Time t (AUC[0-t]) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Maximum Observed Plasma Concentration (Cmax) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Cmax (Tmax) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Apparent Terminal Phase Half-life (t1/2) of Salbutamol	Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.	Pre-dose and post dose 0.05, 0.08, 0.17, 0.25, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24 hours on Day 1 and Day 4
Minimum Observed Serum Potassium Level (Emin, K) After Dosing of Salbutamol	Minimum observed concentration of potassium levels after dose are presented.	0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Weighted Mean Serum Potassium (0-4 Hour) (AUEC, K)	Weighed mean of serum potassium was calculated as summation of each interval. Each interval calculated as: (C2-C1)/2 * (t2-t1), where C2 and t2 are serum potassium and timepoint at the end of each interval, and C1 and t1 are serum potassium and timepoint at the start of each interval.	Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Maximum Observed Heart Rate (Emax, HR) After Dosing of Salbutamol	Maximum observed heart rate (HR) after dose is presented.	0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Weighted Mean Heart Rate (0-4 Hour) (AUEC, HR)	Weighed mean of HR was calculated as summation of each interval. Each interval calculated as: (C2-C1)/2 * (t2-t1), where C2 and t2 are HR and timepoint at the end of each interval, and C1 and t1 are HR and timepoint at the start of each interval.	Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Maximum Observed QTcF (Emax, QTcF) After Dosing of Salbutamol	Maximum observed QTcF after dose are presented.	0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Weighted Mean QTcF (0-4 Hour) (AUEC, QTcF)	Weighed mean of QTcF was calculated as summation of each interval. Each interval calculated as: [(C2+C1)/2×(t2-t1)]/Total time (Tlast-Tfirst, ie 4-0 hour) where C2 and t2 are concentration and timepoint at the end of each interval, and C1 and t1 are concentration and timepoint at the start of each interval. Tlast is the end of the last collection interval, and Tfirst is the start of the first collection interval.	Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is an event that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect. A summary of number of participants with any AEs and SAEs are presented. AEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).	Up to 5 days
Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT (QTc) Interval	A standard 12-lead ECG was obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and QTcF intervals. The ECG was obtained after the participant has been resting for at least 5 minutes in the supine position. Pre-dose 12-lead ECG was measured in triplicate. The 3 pre-dose measures was averaged for QTc interval and HR to derive one baseline value. Each individual capture of the triplicate 12-lead ECG set was separated by 1 to 5 minutes between the first and the third ECG. Baseline is defined as the last observation recorded before the first study drug administration in each dosing period.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTc Interval	A standard 12-lead ECG was obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and QTcF intervals. The ECG was obtained after the participant has been resting for at least 5 minutes in the supine position. Pre-dose 12-lead ECG was measured in triplicate. The 3 pre-dose measures was averaged for QTc interval and HR to derive one baseline value. Each individual capture of the triplicate 12-lead ECG set was separated by 1 to 5 minutes between the first and the third ECG. Screening and post-dose 12-lead ECG measurements were single measurements.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Absolute Values of ECG Parameter: Heart Rate	A standard 12-lead ECG was obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and QTcF intervals. The ECG was obtained after the participant has been resting for at least 5 minutes in the supine position. Pre-dose 12-lead ECG was measured in triplicate. The 3 pre-dose measures was averaged for QTc interval and HR to derive one baseline value. Each individual capture of the triplicate 12-lead ECG set was separated by 1 to 5 minutes between the first and the third ECG. Screening and post-dose 12-lead ECG measurements were single measurements.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Change From Baseline in ECG Parameters: Heart Rate	A standard 12-lead ECG was obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and QTcF intervals. The ECG was obtained after the participant has been resting for at least 5 minutes in the supine position. Pre-dose 12-lead ECG was measured in triplicate. The 3 pre-dose measures was averaged for QTc interval and HR to derive one baseline value. Each individual capture of the triplicate 12-lead ECG set was separated by 1 to 5 minutes between the first and the third ECG. Screening and post-dose 12-lead ECG measurements were single measurements.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Count	Blood samples were collected for analyzing absolute values of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Hematology Parameter: Red Blood Cell (RBC) and Reticulocytes Count	Blood samples were collected for analyzing absolute values of red blood cell (RBC) and reticulocytes count.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Hematology Parameter: Mean Corpuscular Volume (MCV)	Blood samples were collected for analyzing absolute values of Mean Corpuscular Volume (MCV).	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)	Blood samples were collected for analyzing absolute values of Mean corpuscular hemoglobin (MCH).	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Hematology Parameter: Hemoglobin	Blood samples were collected for analyzing absolute values of Hemoglobin.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Hematology Parameter: Hematocrit	Blood samples were collected for analyzing absolute values of Hematocrit.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Phosphokinase (CPK)	Blood samples were collected for analyzing absolute values of Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and Creatine Phosphokinase (CPK).	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine	Blood samples were collected for analyzing absolute values of direct bilirubin, total bilirubin and Creatinine.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Clinical Chemistry Parameter: Total Protein	Blood samples were collected for analyzing absolute values of Total protein.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values for Chemistry Parameters: Calcium, Sodium, Potassium, Blood Urea Nitrogen (BUN)	Blood samples were collected for analyzing absolute values of Calcium, Sodium, Potassium, Blood Urea Nitrogen.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values for Chemistry Parameter: Glucose	Blood samples were collected for analyzing absolute values of glucose.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Number of Participants With Urinalysis Parameters by Dipstick Method	Urine samples were collected to assess glucose, ketones, occult blood, protein, urobilinogen and bilirubin by dipstick method. The dipstick test gave results in a semi-quantitative manner indicating proportional concentrations in the urine sample. Results are presented as'(+)' indicating 'equivocal', '+' indicating 'trace amount', '++' indicating 'positive', and 'negative'.	On Day -1 (admission) and Day 5 (Discharge)
Absolute Values of Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)	Blood pressure measurements were assessed with a completely automated device after the participant has been resting for at least 5 minutes in the supine position. Manual techniques were used only if an automated device was not available.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4
Absolute Values of Pulse Rate	Pulse rate measurements were assessed with a completely automated device after the participant has been resting for at least 5 minutes in the supine position. Manual techniques were used only if an automated device was not available.	Baseline (Pre-dose at Day 1 and Day 4); 0.25, 0.5, 1 hour (h), 1.5 h, 2 h, 4 h post-dose at Day 1 and Day 4

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Actual): May 21, 2023
• Study Completion (Actual): May 21, 2023

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: March 17, 2023
• First Posted (Actual): March 30, 2023

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; Salbutamol; Cross-over
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Anesthetics; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol; Norflurane
• Other Study ID Numbers: 219430

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No