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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Salbutamol HFA-152a
* Drug: Salbutamol HFA-134a


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a 2-way cross-over study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salbutamol HFA-152a MDI followed by Salbutamol HFA-134a MDI<br>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<br>* Salbutamol HFA-152a will be administered.<br>Drug: Salbutamol HFA-134a<br>* Salbutamol HFA-134a will be administered.<br>|
| Experimental: Salbutamol HFA-134a MDI followed by Salbutamol HFA-152a MDI<br>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<br>* Salbutamol HFA-152a will be administered.<br>Drug: Salbutamol HFA-134a<br>* Salbutamol HFA-134a will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) up to 30 minutes post-dose (AUC[0-30 minute]) of salbutamol |  | Pre-dose and at 3, 5, 10, 15, 20 and 30 minutes post-dose on Days 1 and 4 | 
| AUC from time 0 to infinity (AUC[0-inf]) of salbutamol |  | Up to Day 5 | 
| AUC from time 0 to time t (AUC[0-t]) of salbutamol |  | Up to Day 5 | 
| Maximum observed plasma concentration (Cmax) of salbutamol |  | Up to Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cmax (Tmax) of salbutamol |  | Up to Day 5 | 
| Apparent terminal phase half-life (t1/2) of salbutamol |  | Up to Day 5 | 
| Minimum serum potassium level following administration of salbutamol |  | Up to Day 5 | 
| Weighted mean (0-4 hours) serum potassium level following administration of salbutamol |  | Pre-dose and at 15 minutes, 30 minutes, 1, 1.5, 2 and 4 hours post-dose on Days 1 and 4 | 
| Maximum heart rate following administration of Salbutamol |  | Up to Day 5 | 
| Weighted mean (0-4 hours) heart rate following administration of Salbutamol |  | Pre-dose and at 15 minutes, 30 minutes, 1, 1.5, 2 and 4 hours post-dose on Days 1 and 4 | 
| Maximum corrected QT (QTc) interval following administration of Salbutamol |  | Up to Day 5 | 
| Weighted mean (0-4 hours) QTc interval following administration of Salbutamol |  | Pre-dose and at 15 minutes, 30 minutes, 1, 1.5, 2 and 4 hours post-dose on Days 1 and 4 | 
| Number of participants with non-serious adverse events and serious adverse events |  | Up to Day 5 | 
| Absolute values of Electrocardiogram (ECG) parameters: PR interval, QRS duration, QT interval and corrected QT (QTc) interval (Milliseconds) |  | Up to Day 5 | 
| Change from Baseline in ECG parameters: PR interval, QRS duration, QT interval and QTc interval (Milliseconds) |  | Baseline and up to Day 5 | 
| Absolute values of ECG parameter: Heart rate (Beats per minute) |  | Up to Day 5 | 
| Change from Baseline in ECG parameters: Heart rate (Beats per minute) |  | Baseline and up to Day 5 | 
| Absolute values of hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet count (Giga cells per liter) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Red blood cell (RBC) count (Trillion cells per liter) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Mean Corpuscular Volume (MCV) (Femtoliters) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Mean corpuscular hemoglobin (MCH) (Picograms) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Percentage of reticulocytes (Percentage of reticulocytes) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Hemoglobin (Grams per Liter) |  | Up to Day 5 | 
| Absolute values of hematology parameter: Hematocrit (Proportion of red blood cells in blood) |  | Up to Day 5 | 
| Absolute values of clinical chemistry parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and Creatine Phosphokinase (CPK) (International units per Liter) |  | Up to Day 5 | 
| Absolute values of clinical chemistry parameters: direct bilirubin, total bilirubin and Creatinine (Micromoles per liter) |  | Up to Day 5 | 
| Absolute values of clinical chemistry parameter: Total protein (Grams per liter) |  | Up to Day 5 | 
| Absolute Values for Chemistry Parameters: Glucose, Calcium, Sodium, Potassium, Blood Urea Nitrogen (Millimoles per liter) |  | Up to Day 5 | 
| Number of participants with abnormal urinalysis parameters by Dipstick Method |  | Up to Day 5 | 
| Absolute values of diastolic blood pressure (DBP) and systolic blood pressure (SBP) (Millimeters of mercury [mmHg]) |  | Up to Day 5 | 
| Absolute values of pulse rate (Beats per minute) |  | Up to Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cross-over, Healthy volunteers, Salbutamol, Pharmacokinetics