Clinical trial NCT05472662: A Study to Compare the Effects of Two Propellants in Adults With Mild Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2022-07-25
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Relative Change From Baseline* in Forced Expiratory Volume in 1 s (FEV1) -- 15 Min Post-dose
timeFrame: At 15 min post-dose after T1.
Secondary outcomes:
measure: Safety: Safety: Relative Change From Baseline* in FEV1 -- All Other Post-dose Time Points
timeFrame: At 5 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
measure: Safety: Absolute Change From Baseline* in FEV1 -- All Time Points Post Dose
timeFrame: At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
measure: Safety: Subjects With a Relative Change From Baseline* in FEV1 <-15% -- All Post-dose Time Points
timeFrame: At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
measure: Safety: Change From Baseline* in FEV1 Area Under the Concentration-time Curve From Time Zero to 3 Hours (AUC0-3h)
timeFrame: At 3 h post-dose.
measure: Safety: Relative Change From Baseline* in Peak Expiratory Flow (PEF) -- All Post-dose Time Points
timeFrame: At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
measure: Safety: Absolute Change From Baseline* in PEF -- All Post-dose Time Points
timeFrame: At 5 min, 15 min, 30 min, 1 h, 1 h 30 min, and 3 h after T1.
measure: Safety: Subjects With Use of Rescue Medication -- 3 h Post Dose
timeFrame: 3 h post-dose.
measure: Safety and Tolerability: Vital Signs -- Diastolic Blood Pressure
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
measure: Safety and Tolerability: Vital Signs -- Systolic Blood Pressure
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
measure: Safety and Tolerability: ECG Parameter -- Heart Rate
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
measure: Safety and Tolerability: ECG Parameter -- PR Interval
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
measure: Safety and Tolerability: ECG Parameter -- QRS
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
measure: Safety and Tolerability: ECG Parameter -- QTcF Interval
timeFrame: At 45 min, 1.75 h, 2.75 h post dose.
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Medicine Evaluation Unit Limited
Study officials:
affiliation: Medicines Evaluation Unit
name: Dave Singh, MD
role: PRINCIPAL_INVESTIGATOR
References: