Clinical trial NCT05791565: Green (Sustainable) VENTOLIN - Pharmacokinetics (PK) Study in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Cross-over
Healthy volunteers
Salbutamol
Pharmacokinetics
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2023-03-30
Enrollment: 28
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: This is a 2-way cross-over study.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC (0-30 Min)) of Salbutamol
timeFrame: Pre-dose and post dose 3, 5, 10, 15, 20 and 30 minutes on Day 1 and Day 4
measure: AUC From Time 0 to Infinity (AUC[0-inf]) of Salbutamol
timeFrame: 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
measure: AUC From Time 0 to Time t (AUC[0-t]) of Salbutamol
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Salbutamol
timeFrame: 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:
measure: Time to Cmax (Tmax) of Salbutamol
timeFrame: 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
measure: Apparent Terminal Phase Half-life (t1/2) of Salbutamol
timeFrame: 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
measure: Minimum Observed Serum Potassium Level (Emin, K) After Dosing of Salbutamol
timeFrame: 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Weighted Mean Serum Potassium (0-4 Hour) (AUEC, K)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Maximum Observed Heart Rate (Emax, HR) After Dosing of Salbutamol
timeFrame: 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Weighted Mean Heart Rate (0-4 Hour) (AUEC, HR)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Maximum Observed QTcF (Emax, QTcF) After Dosing of Salbutamol
timeFrame: 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Weighted Mean QTcF (0-4 Hour) (AUEC, QTcF)
timeFrame: Pre-dose and 0.25, 0.5, 1, 1.5, 2 and 4 hours post-dose on each dosing day (Days 1 and 4)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 5 days
measure: Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT (QTc) Interval
timeFrame: 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
measure: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTc Interval
timeFrame: 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
measure: Absolute Values of ECG Parameter: Heart Rate
timeFrame: 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
measure: Change From Baseline in ECG Parameters: Heart Rate
timeFrame: 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
measure: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Count
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Hematology Parameter: Red Blood Cell (RBC) and Reticulocytes Count
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Hematology Parameter: Mean Corpuscular Volume (MCV)
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Hematology Parameter: Hemoglobin
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Hematology Parameter: Hematocrit
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Phosphokinase (CPK)
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Clinical Chemistry Parameter: Total Protein
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values for Chemistry Parameters: Calcium, Sodium, Potassium, Blood Urea Nitrogen (BUN)
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values for Chemistry Parameter: Glucose
timeFrame: 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
measure: Number of Participants With Urinalysis Parameters by Dipstick Method
timeFrame: On Day -1 (admission) and Day 5 (Discharge)
measure: Absolute Values of Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: 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
measure: Absolute Values of Pulse Rate
timeFrame: 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
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: