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

GlaxoSmithKline28 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Asthma

Interventions

Salbutamol HFA-152aDRUG

Salbutamol HFA-152a will be administered.

Salbutamol HFA-134aDRUG

Salbutamol HFA-134a will be administered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

GSK Investigational Site

Groningen, Netherlands

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 Outcomes

Time to Cmax (Tmax) of Salbutamol

Blood samples were collected for pharmacokinetic (PK) analysis. PK parameter was determined using standard non-compartmental methods.

Time frame: 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

Data from ClinicalTrials.gov

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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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.