## Protocol Section
### Identification Module
**NCT ID:** NCT06433908

**Brief Title:** 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)

#### Organization Study ID Info
**ID:** 219728
#### Organization
**Class:** INDUSTRY
**Full Name:** GlaxoSmithKline
#### Secondary ID Infos
**Domain:** EU CT number
**ID:** 2023-508279-36-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2024-09-27

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-09-13

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-27

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-23
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** GlaxoSmithKline

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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).

### Conditions Module

**Conditions:**

- Asthma

- Healthy Participants

**Keywords:**

- salbutamol

- propellant HFA-152a

- propellant HFA-134a

- metered dose inhalers

- healthy participants

- asthma

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** 4-way crossover study.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive single 200 μg doses given as 2x100 μg (ex-valve) at 20-second intervals. The intervention period will be 10 days with dosing with either HFA-152a or HFA-134a on Day 1, Day 4, Day 7, and Day 10.

**Intervention Names:**

- Drug: Salbutamol HFA-152a

- Drug: Salbutamol HFA-134a

**Label:** Cohort 1: Salbutamol 200 μg

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive single 800 μg doses given as 8x100 μg (ex-valve) at 20-second intervals. The intervention period will be 10 days with dosing with either HFA-152a or HFA-134a on Day 1, Day 4, Day 7, and Day 10.

**Intervention Names:**

- Drug: Salbutamol HFA-152a

- Drug: Salbutamol HFA-134a

**Label:** Cohort 2: Salbutamol 800 μg

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Cohort 1: Salbutamol 200 μg

- Cohort 2: Salbutamol 800 μg

**Description:** 100 µg (ex-valve), given at 20-second intervals.

**Name:** Salbutamol HFA-152a

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Cohort 1: Salbutamol 200 μg

- Cohort 2: Salbutamol 800 μg

**Description:** 100 µg (ex-valve), given at 20-second intervals.

**Name:** Salbutamol HFA-134a

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Area Under the Plasma Concentration-time Curve up to 30 Minutes Post-dose (AUC[0-30min])

**Time Frame:** 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-∞])

**Time Frame:** 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)

**Time Frame:** 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)

**Time Frame:** 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)

**Time Frame:** 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])

**Time Frame:** 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)

**Time Frame:** 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-∞)

**Time Frame:** 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)

**Time Frame:** 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

**Time Frame:** 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)

**Time Frame:** Up to Day 18

**Measure:** Absolute Values for 12 Lead Electrocardiogram (ECGs) Recording of Heart Rate (HR)

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** 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

**Time Frame:** Day-1 (admission) up to discharge (Day 11)

**Measure:** Absolute Values of Vital Signs (Systolic and Diastolic Blood Pressure)

**Time Frame:** 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)

**Time Frame:** 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)

### Eligibility Module

**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.

**Healthy Volunteers:** True

**Maximum Age:** 55 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** US GSK Clinical Trials Call Center

**Phone:** 877-379-3718

**Role:** CONTACT

**Contact 2:**

**Email:** GSKClinicalSupportHD@gsk.com

**Name:** EU GSK Clinical Trials Call Center

**Phone:** +44 (0) 20 89904466

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Groningen

**Contacts:**

***Contact 1:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** US GSK Clinical Trials Call Center

- **Phone:** 877-379-3718

- **Role:** CONTACT

***Contact 2:***

- **Email:** GSKClinicalSupportHD@gsk.com

- **Name:** EU GSK Clinical Trials Call Centre

- **Phone:** +44 (0) 20 8990 4466

- **Role:** CONTACT

***Contact 3:***

- **Name:** Jeroen van de Wetering

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Netherlands

**Facility:** GSK Investigational Site

**Zip:** 9728

### IPD Sharing Statement Module

**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.

**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/

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

- CSR

**IPD Sharing:** YES

**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.

**URL:** https://www.gsk.com/en-gb/innovation/trials/data-transparency/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001982

- Term: Bronchial Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000008173

- Term: Lung Diseases, Obstructive

- ID: D000008171

- Term: Lung Diseases

- ID: D000012130

- Term: Respiratory Hypersensitivity

- ID: D000006969

- Term: Hypersensitivity, Immediate

- ID: D000006967

- Term: Hypersensitivity

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M4556

- Name: Asthma

- Relevance: HIGH

- As Found: Asthma

- ID: M5258

- Name: Bronchial Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11170

- Name: Lung Diseases, Obstructive

- Relevance: LOW

- As Found: Unknown

- ID: M10018

- Name: Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M14967

- Name: Respiratory Hypersensitivity

- Relevance: LOW

- As Found: Unknown

- ID: M10020

- Name: Hypersensitivity, Immediate

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001249

- Term: Asthma

### Intervention Browse Module - Ancestors

- ID: D000001993

- Term: Bronchodilator Agents

- ID: D000001337

- Term: Autonomic Agents

- ID: D000018373

- Term: Peripheral Nervous System Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000018927

- Term: Anti-Asthmatic Agents

- ID: D000019141

- Term: Respiratory System Agents

- ID: D000015149

- Term: Tocolytic Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000058666

- Term: Adrenergic beta-2 Receptor Agonists

- ID: D000000318

- Term: Adrenergic beta-Agonists

- ID: D000000322

- Term: Adrenergic Agonists

- ID: D000018663

- Term: Adrenergic Agents

- ID: D000018377

- Term: Neurotransmitter Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000777

- Term: Anesthetics

- ID: D000002492

- Term: Central Nervous System Depressants

### Intervention Browse Module - Browse Branches

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: Resp

- Name: Respiratory System Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaCoAg

- Name: Vasoconstrictor Agents

- Abbrev: CaAg

- Name: Cardiotonic Agents

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

### Intervention Browse Module - Browse Leaves

- ID: M3767

- Name: Albuterol

- Relevance: HIGH

- As Found: Residual

- ID: M13031

- Name: Oxymetazoline

- Relevance: LOW

- As Found: Unknown

- ID: M13561

- Name: Phenylephrine

- Relevance: LOW

- As Found: Unknown

- ID: M353106

- Name: Norflurane

- Relevance: HIGH

- As Found: Aldara

- ID: M5269

- Name: Bronchodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20963

- Name: Anti-Asthmatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M21137

- Name: Respiratory System Agents

- Relevance: LOW

- As Found: Unknown

- ID: M17869

- Name: Tocolytic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20746

- Name: Adrenergic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M3670

- Name: Adrenergic beta-Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M3673

- Name: Adrenergic Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M20504

- Name: Neurotransmitter Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4107

- Name: Anesthetics

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000063006

- Term: Norflurane

- ID: D000000420

- Term: Albuterol

### Misc Info Module

- Version Holder: 2024-05-31
