A Study to Compare the Effects of Two Propellants in Adults With Mild Asthma

A Single-dose, Randomised, Double-blind, Controlled, 2-way Cross-over Study to Assess the Potential for Bronchoconstriction of the New Propellant HFA-152a Versus the Marketed HFA-134a Propellant, in Adult Subjects With Mild Asthma

This is a Phase IIa, multicentre, single dose, randomised, double blind, controlled, 2 way cross-over study to evaluate the potential for bronchoconstriction of the new HFA-152a propellant (single dose) versus the marketed HFA-134a propellant (single dose) in adults with mild asthma.

HFA=Hydrofluoroalkane

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo 152a; Drug: Placebo 134a

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Medicine Evaluation Unit Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject's written informed consent obtained prior to any study related procedure.
2. Gender and age: Male or female adults aged from 18 to 75 years old (inclusive).
3. Diagnosis of asthma: documented established diagnosis of mild asthma for at least 6 months according to Step 1 of the Global Initiative for Asthma (GINA) 2021 guidelines.
4. Lung function: subjects with a pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≥60% of the predicted normal value and ≥1.5 L at screening and prior to randomisation, after appropriate wash-out from bronchodilators.
5. Documented excessive variability in lung function.
6. Current asthma therapy: as needed low-dose inhaled corticosteroids (ICS)-formoterol, as needed short-acting β2-agonists (SABA), or low-dose ICS whenever SABA was taken taken not more than twice a week (2 events) in the 4 weeks prior to screening or in the 6 weeks prior to randomisation.
7. Asthma control: controlled or partly controlled based on an Asthma Control Questionnaire© (ACQ-5) score <1.5 at screening and prior to randomisation.
8. Ability to use the inhalers.
9. Ability to comply with the protocol. 10: Female subjects of non-childbearing potential (defined as physiologically incapable of becoming pregnant (i.e. postmenopausal or permanently sterile) and Female subjects of childbearing potential, who accepts the use of highly effective contraceptive methods during the study or with non-fertile male partners.

11. Male subjects fulfilling one of the following criteria:

1. Fertile male subjects with pregnant or non-pregnant women of childbearing potential (WOCBP) partners: they must be willing to use male condom from the signature of the Informed Consent Form (ICF) and until the follow-up visit/call, or;
2. Non-fertile male subjects (contraception is not required in this case), or;

3. Fertile male subjects with women of non-childbearing potential (WONCBP) partner (contraception is not required in this case).

   Exclusion criteria:

   1. History of "at risk" asthma.
   2. Recent exacerbation.
   3. Asthma requiring use of biologics.
   4. Respiratory disorders other than asthma.
   5. Lung cancer or history of lung cancer.
   6. Lung resection.
   7. Lower respiratory tract infection.
   8. Documented coronavirus disease 2019 (COVID-19) diagnosis.
   9. Smoking status: current smoker, or ex-smoker with a smoking history of ≥10 pack-years.
   10. Cancer or history of cancer (other than lung cancer);subject with active cancer or a history of cancer with less than 5 years disease-free survival time.
   11. Cardiovascular diseases: subjects who have known and clinically significant (CS) cardiovascular conditions.
   12. Electrocardiogram (ECG) criteria: any CS abnormal 12-lead ECG that, in the Investigator's opinion, would affect safety evaluations or place the subject at risk.
   13. Central nervous system disorders: subjects with a history of symptoms or significant neurological disease.
   14. Other concurrent diseases: subjects with historical or current evidence of uncontrolled concurrent disease such as, but not limited to, hyperthyroidism, diabetes mellitus or other endocrine disease, haematological disease, autoimmune disorders (e.g. rheumatoid arthritis), gastrointestinal disorders (e.g. poorly controlled peptic ulcer, gastroesophageal reflux disease), significant renal impairment or other disease or condition that might, in the judgement of the Investigator, place the subject at undue risk or potentially compromise the results or interpretations of the study.
   15. Laboratory abnormalities: subjects with CS laboratory abnormalities indicating a significant or unstable concomitant disease.
   16. Alcohol/drug abuse.
   17. Participation to investigational trial: subjects who have received any investigational drug within the 30 days (60 days for biologics) prior to screening.

   16. Hypersensitivity: history of hypersensitivity to any of the study medications components.

   17.Subjects mentally or legally incapacitated. 18. Recent eye surgery or any condition where raised intracranial pressure (caused by forceful exhalation) would be harmful.

   19. For female subjects only: pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until termination of the gestation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test; Placebo HFA-152a propellant via pressurised metered-dose inhaler (pMDI): Administration: Single-dose administration.	Drug: Placebo 152a; Placebo pressurised metered-dose inhaler (pMDI) formulated with the 152a propellant
Placebo Comparator: Reference; Placebo HFA-134a propellant via pressurised metered-dose inhaler (pMDI): Administration: Single-dose administration.	Drug: Placebo 134a; Placebo pressurised metered-dose inhaler (pMDI) formulated with the 134a propellant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Relative Change From Baseline* in Forced Expiratory Volume in 1 s (FEV1) -- 15 Min Post-dose	Safety: Relative change from baseline* in forced expiratory volume in 1 s (FEV1) at the 15 min post-dose time point. Results are presented as adjusted mean and 95% confidence interval (CI.) The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. *The baseline FEV1 values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 15 min post-dose after T1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Safety: Relative Change From Baseline* in FEV1 -- All Other Post-dose Time Points	Safety: Relative change from baseline* in FEV1 at all the other post-dose time points (5 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1). Results are presented as adjusted mean and 95% CI. The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. *The baseline FEV1 values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 5 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
Safety: Absolute Change From Baseline* in FEV1 -- All Time Points Post Dose	Safety: Absolute change from baseline* in FEV1 at all post-dose time points. Results are presented as adjusted mean and 95% CI. The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. The baseline FEV1 values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
Safety: Subjects With a Relative Change From Baseline* in FEV1 <-15% -- All Post-dose Time Points	Safety: Number and percentage of subjects with a relative change from baseline* in FEV1 at each post-dose time point <-15%. The baseline FEV1 values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
Safety: Change From Baseline* in FEV1 Area Under the Concentration-time Curve From Time Zero to 3 Hours (AUC0-3h)	Change from baseline* in FEV1 area under the concentration-time curve from time zero to 3 hours (AUC0-3h). Results show the change from baseline in FEV1 AUC(0-3h) corrected for Time, in litres The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. *The baseline FEV1 values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 3 h post-dose.
Safety: Relative Change From Baseline* in Peak Expiratory Flow (PEF) -- All Post-dose Time Points	Safety: Relative change from baseline* in peak expiratory flow (PEF) at all post-dose time points. The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. The baseline PEF values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
Safety: Absolute Change From Baseline* in PEF -- All Post-dose Time Points	Safety: Absolute change from baseline* in PEF at all post-dose time points. The potential of the test propellant (HFA-152a vs HFA-134a) for bronchoconstriction was evaluated using centralised spirometry assessments performed during treatment period 1 (TP1) and treatment period 2 (TP2). T0 was defined as the moment when the first inhalation took place, and was used to calculate the pre-dose time points. T1 was defined as the moment when the last inhalation took place, and was used to calculate the post-dose time points. The baseline PEF values were the mean of the two pre-dose assessments (i.e., performed at 45 min and 15 min before T0).	At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
Safety: Subjects With Use of Rescue Medication -- 3 h Post Dose	Number and percentage of subjects with use of rescue medication in the 3 h post dose.	3 h post-dose.
Safety and Tolerability: Vital Signs -- Diastolic Blood Pressure	Safety and tolerability: Mean change from baseline in the Vital Signs -- Diastolic Blood Pressure	At 45 min, 1.75 h, 2.75 h post dose.
Safety and Tolerability: Vital Signs -- Systolic Blood Pressure	Safety and tolerability: Mean change from baseline in the Vital Signs -- Systolic Blood Pressure	At 45 min, 1.75 h, 2.75 h post dose.
Safety and Tolerability: ECG Parameter -- Heart Rate	Safety and tolerability: Mean change from baseline in the ECG parameter -- Heart rate	At 45 min, 1.75 h, 2.75 h post dose.
Safety and Tolerability: ECG Parameter -- PR Interval	Safety and tolerability: Mean change from baseline in the ECG parameter -- PR interval.	At 45 min, 1.75 h, 2.75 h post dose.
Safety and Tolerability: ECG Parameter -- QRS	Safety and tolerability: Mean change from baseline in the ECG parameter -- QRS interval.	At 45 min, 1.75 h, 2.75 h post dose.
Safety and Tolerability: ECG Parameter -- QTcF Interval	Safety and tolerability: Mean change from baseline in the ECG parameter -- QTcF interval.	At 45 min, 1.75 h, 2.75 h post dose.

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Dave Singh, MD, Medicines Evaluation Unit

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Actual): October 31, 2022
• Study Completion (Actual): October 31, 2022

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CLI-05993AB6-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No