## Protocol Section
### Identification Module
**NCT ID:** NCT06433921

**Brief Title:** A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive

**Official Title:** A Phase 1, Randomized, 2-part, 7-way Cross-over (Part 1) and 7-way Cross-over (Part 2), Active Device Blinded, Single Dose Study in Mild Asthmatics Aged 18-65 to Assess the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers Containing Propellants HFA-152a (Test) and HFA-134a (Reference) Via Methacholine Bronchoprovocation and Systemic Pharmacodynamic Effects

#### Organization Study ID Info
**ID:** 219729
#### Organization
**Class:** INDUSTRY
**Full Name:** GlaxoSmithKline
#### Secondary ID Infos
**Domain:** EU CT number
**ID:** 2024-511220-14-00
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2024-10-15

**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:** 2024-10-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-04

**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 objectives of the study are:

* Part 1: to characterize the potency and variability of dose response on efficacy (Provocative concentration of methacholine causing at least a 20% fall in forced expiratory volume (FEV1) \[PC20\]) of salbutamol administered via MDI with salbutamol HFA-134a or salbutamol HFA-152a in participants with mild asthma.
* Part 2: to compare the comparative dose response on efficacy (PC20) of salbutamol when administered via MDI with salbutamol HFA-134a or salbutamol HFA-152a in participants with mild asthma.

### Conditions Module

**Conditions:**

- Asthma

- Mild Asthma

**Keywords:**

- salbutamol

- propellant HFA-152a

- propellant HFA-134a

- metered dose inhalers

- mild asthma

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** 2-part, 7-way cross-over (Part 1) and up to 7-way cross-over (Part 2).

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 91

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Part 1 will consist of a 7 treatment, 7 period cross-over evaluation with all participants receiving the following treatments once, randomized to varying pre-specified sequences of:

* Zero dose (placebo of both salbutamol HFA-134a and salbutamol HFA-152a)
* 100 μg salbutamol HFA-134a
* 200 μg salbutamol HFA-134a
* 400 μg salbutamol HFA-134a
* 100 μg salbutamol HFA-152a
* 200 μg salbutamol HFA-152a
* 400 μg salbutamol HFA-152a

A minimum of a 2-day and maximum of a 7-day methacholine washout will separate each treatment period.

**Intervention Names:**

- Drug: Salbutamol HFA-152a

- Drug: Salbutamol HFA-134a

- Drug: Placebo

**Label:** Part 1

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Part 2 is proposed to consist of up to a 7 treatment, 7-way cross-over pivotal evaluation with the following treatments given once, randomized to varying pre-specified sequences of:

* Zero dose (placebo of both salbutamol HFA-134a and salbutamol HFA-152a)
* 100 μg salbutamol HFA-134a
* 200 μg salbutamol HFA-134a
* 400 μg salbutamol HFA-134a
* 100 μg salbutamol HFA-152a
* 200 μg salbutamol HFA-152a
* 400 μg salbutamol HFA-152a

A minimum of a 2-day and maximum of a 7-day methacholine washout will separate each treatment period.

**Intervention Names:**

- Drug: Salbutamol HFA-152a

- Drug: Salbutamol HFA-134a

- Drug: Placebo

**Label:** Part 2

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Part 1

- Part 2

**Description:** A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.

**Name:** Salbutamol HFA-152a

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Part 1

- Part 2

**Description:** A single 100, 200 or 400 μg dose, given as 1, 2 or 4 × 100 μg actuations (exvalve) at 20 second intervals.

**Name:** Salbutamol HFA-134a

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Part 1

- Part 2

**Description:** A single placebo HFA-152a suspension or placebo HFA-134a suspension dose, given as at 20 second intervals.

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** PC of methacholine causing at least a 20% fall in FEV1.

**Measure:** PC20

**Time Frame:** Up to 11 weeks

#### Secondary Outcomes

**Measure:** Peak QTc Interval

**Time Frame:** Up to 11 weeks

**Measure:** Peak Heart Rate (HR)

**Time Frame:** Up to 11 weeks

**Measure:** Minimum Serum Potassium

**Time Frame:** Up to 11 weeks

**Measure:** Maximum Observed Plasma Concentration (Cmax)

**Time Frame:** Up to 11 weeks

**Measure:** Time to Reach Cmax (Tmax)

**Time Frame:** Up to 11 weeks

**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:** Up to 11 weeks

**Measure:** Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

**Time Frame:** Up to 11 weeks

**Measure:** Absolute Values for 12-lead Electrocardiogram (ECG) Recording of HR

**Time Frame:** Up to 11 weeks

**Description:** Intervals recorded:

* PR
* QRS
* QT
* QTc

**Measure:** Absolute Values for 12-lead ECGs Recording of Intervals

**Time Frame:** Up to 11 weeks

**Description:** The 3 predose measures will be recorded and will be averaged for HR to derive 1 baseline value.

**Measure:** Change from Baseline for Post-dose 12-lead ECGs Recording of HR

**Time Frame:** Baseline and up to 11 weeks

**Description:** The 3 predose measures will be recorded and will be averaged for QTc interval to derive 1 baseline value.

Intervals recorded:

* PR
* QRS
* QT
* QTc

**Measure:** Change from Baseline for Post-dose 12-lead ECGs Recording of Intervals

**Time Frame:** Baseline and up to 11 weeks

**Measure:** Number of Participants with Clinically Significant Changes in Clinical Laboratory Parameters

**Time Frame:** Up to 11 weeks

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

**Time Frame:** Up to 11 weeks

**Measure:** Absolute Values of Vital Signs (Pulse Rate)

**Time Frame:** Up to 11 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Male or female; females may be of childbearing potential, of nonchildbearing potential, or postmenopausal.
2. Participant must be 18 to 65 years of age inclusive, at the time of screening.
3. ≥50 kg, at the time of screening.
4. Documented history of asthma ≥ 6 months.
5. Receiving 1 of following asthma treatments, at a stable dose, for at least 12 weeks prior to the screening visit and is anticipated to remain stable for the duration of the study:

   i. Short-acting beta-agonist (SABA) only. ii. Daily maintenance low-dose inhaled corticosteroids (ICS) (defined as 100-250 μg/day fluticasone propionate or equivalent plus or minus SABA which is anticipated to remain stable for the duration of the study.

   iii. Daily maintenance low-dose ICS + Long-acting beta-2 agonist (LABA) therapy (low-dose ICS defined as 100-250 μg/day fluticasone propionate or equivalent as defined by GINA \[GINA, 2023\]) plus or minus SABA, which is anticipated to remain stable for the duration of the study.
6. No severe asthma exacerbations within 6 months prior to screening and ≤1 severe exacerbation during the 12 months prior to screening.
7. Pre-bronchodilator FEV1 ≥80% of predicted, at screening
8. PC20 to methacholine of ≤8 mg/mL, at screening.
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and Is a woman of woman of nonchildbearing potential (WONCBP) OR ii. Is a woman of child bearing potential (WOCBP) and using a contraceptive method that is highly effective.
10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
11. Non-smokers who have not used any tobacco containing-products within 12 months prior to study start, and with a total pack year history of ≤10 pack years.

Exclusion Criteria:

1. Medical Conditions

   1. A history of life-threatening asthma or asthma that is unstable in the opinion of the investigator.
   2. A history of respiratory diseases to include (but not limited to): pneumothorax, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, cystic fibrosis, bronchiectasis, interstitial lung disease, emphysema, chronic obstructive pulmonary disease, tuberculosis, or other respiratory abnormalities other than asthma.
   3. Asymptomatic gallstones.
   4. History or current evidence of hematologic, neurologic, psychiatric, or other diseases that, in the opinion of the investigator, would put the participant at risk through study participation, or would affect the study analyses if the disease exacerbates during the study.
   5. Recent eye surgery or any other condition in which raised intracranial pressure (caused by forceful exhalation) would be harmful.
   6. Current use of cholinesterase inhibitor medication e.g., to treat myasthenia gravis.
2. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day or participation in a clinical study within 30 days of study start, or 5 half-lives of study drug if that is longer.
3. Participants who are currently or in the last 15 days have worked nightshifts.
4. Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of \>21 units for males or \>14 units for females.
5. A positive test result for drugs of abuse (including tetrahydrocannabinol) at screening or Day -1.
6. Use of combustible tobacco products, and non-combustible nicotine delivery systems, inclusive of cigarettes, cigars, pipes, and materials used to "vape" within 12 months prior to the start of the study.

**Maximum Age:** 65 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_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

### 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

- Abbrev: Rare

- Name: Rare Diseases

### 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

- ID: T4202

- Name: Oculocerebral Syndrome With Hypopigmentation

- 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: CNSDep

- Name: Central Nervous System Depressants

### Intervention Browse Module - Browse Leaves

- ID: M3767

- Name: Albuterol

- Relevance: HIGH

- As Found: Residual

- ID: M18666

- Name: Methacholine Chloride

- 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
