Study to Assess Effect of HFO MDI Propellant on Mucociliary Clearance Vs. HFA MDI Propellant in Healthy Participants

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Capable of giving signed informed consent as described in the protocol whichincludes compliance with the requirements and restrictions listed in the informedconsent form (ICF) and in this protocol.

2. Healthy non-smoking male and/or female participants aged 18 to 60 years inclusive atthe time of signing the informed consent, without respiratory comorbidities.

3. Participant must have a forced expiratory volume in 1 second (FEV1) ≥ 80% of thepredicted value for age, height, and ethnicity at screening, and FEV1/forced vitalcapacity (FVC) ratio of > 70%.

4. Participant must demonstrate acceptable MDI administration using empty training MDI.

5. Participant willing to comply with study IP administration requirements, defined as ≥ 80% participant medication adherence during the Treatment Periods.

6. Body mass index (BMI) within the range 18 to 35 kg/m2 (inclusive), and weight withinthe range 50 to 120 kg (inclusive).

7. Female participants must be not of childbearing potential or must use a form ofhighly effective birth control as defined below:

(a) Women not of childbearing potential are defined as women who are eitherpermanently sterilized (hysterectomy, bilateral oophorectomy, or bilateralsalpingectomy), or who are postmenopausal. Women will be considered postmenopausalif they have been amenorrheic for 12 months prior to the planned date ofrandomization without an alternative medical cause. The following age-specificrequirements apply:

• Women < 50 years old would be considered postmenopausal if they have beenamenorrheic for 12 months or more following cessation of exogenous hormonaltreatment and follicle stimulating hormone (FSH) levels in the postmenopausalrange.

• Women ≥ 50 years old would be considered postmenopausal if they have beenamenorrheic for 12 months or more following cessation of all exogenous hormonaltreatment.

8. Female participants of childbearing potential must use one highly effective form ofbirth control. A highly effective method of contraception is defined as one that canachieve a failure rate of less than 1% per year when used consistently andcorrectly. At enrollment, women of childbearing potential who are sexually activewith a non-sterilized male partner should be stable on their chosen method of highlyeffective birth control, as defined below, and willing to remain on the birthcontrol until at least 14 days after last dose of study intervention. Cessation ofcontraception after this point should be discussed with a responsible physician.Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are notacceptable methods of contraception. Female condom and male condom should not beused together.

• All women of childbearing potential must have a negative serum pregnancy testresult at Visit 1.

• Females <50 years of age with amenorrhea for 12 months without analternative medical cause must have a serum FSH test at Visit 1.

• Highly effective birth control methods are listed below:

• Total sexual abstinence is an acceptable method provided it is the usuallifestyle of the participant (defined as refraining from heterosexualintercourse during the entire period of risk associated with the studytreatments).

• Combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation:

• Oral

• Intravaginal

• Transdermal

• Progestogen-only hormonal contraception associated with inhibition ofovulation:

• Oral

• Injectable

• Implantable

• Intrauterine device or intrauterine hormone-releasing system

• Bilateral tubal occlusion

• Male partner sterilization/vasectomy with documentation of azoospermia prior tothe female participant's entry into the study, and this male is the solepartner for that participant. The documentation on male sterility can come fromthe site personnel's review of participant's medical records, medicalexamination and/or semen analysis or medical history interview provided by heror her partner.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. History of smoking > 10 pack-years, or participant quit smoking < 6 months prior toscreening.

2. Acute or chronic upper or lower respiratory illness within 30 days of screening.

3. Respiratory medication or medication impacting ciliary clearance for any indicationwithin 30 days of screening.

4. History of more than 2 chest CTs or equivalent (> 10 mSv) within the past year.

5. History of any clinically significant disease or disorder which, in the opinion ofthe investigator, may either put the participant at risk because of participation inthe study, or influence the results or the participant's ability to participate inthe study.

6. Any clinically significant illness, medical/surgical procedure, or trauma within 4weeks of the first administration of the IP.

7. History of any cancer except squamous cell and basal cell carcinomas of the skin.

8. Any clinically significant abnormalities in clinical chemistry, hematology, orurinalysis results, at screening as judged by the investigator.

9. Any clinically significant abnormal findings in vital signs at screening, as judgedby the investigator.

10. Any clinically significant abnormalities on 12-lead ECG at screening, as judged bythe investigator. Note: Participants with ECG QT interval corrected for heart rateusing Fridericia's formula (QTcF) > 480 msec will be excluded.

11. A SARS-CoV-2 infection in the 8 weeks prior to Visit 1, or during the ScreeningPeriod, or that required hospitalization at any time prior to Visit 1 or during theScreening Period.

12. Participant has clinical signs and symptoms consistent with SARS-CoV-2 infection;eg, fever, dry cough, dyspnea, sore throat, fatigue, or laboratory-confirmed acuteinfection with SARS-CoV-2.

13. Participant who had severe course of COVID-19 (extracorporeal membrane oxygenation,mechanically ventilated, Intensive Care Unit stay).

14. History of any respiratory disorders such as asthma, chronic obstructive pulmonarydisease, or idiopathic pulmonary fibrosis, alpha-1 antitrypsin, primary ciliarydyskinesia, cystic fibrosis.

15. Known or suspected history of drug abuse, as judged by the investigator.

16. Current smokers or those who have smoked or used nicotine products (includingelectronic cigarettes) marijuana, vaping, etc, within the 6 months prior toscreening.

17. Positive screen for drugs of abuse or cotinine at screening.

18. Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose of vitamins (intake of 20 to 600 times the recommended daily dose), and minerals within 14 daysor 5 half-lives (whichever is longer) prior to the first administration of IP.

19. Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate)as judged by the investigator. Excessive intake of caffeine defined as the regularconsumption of more than 600 mg of caffeine per day (eg, > 5 cups of coffee) orwould likely be unable to refrain from the use of caffeine-containing beverages.

20. Using any herbal products either by inhalation or by nebulizer within 2 weeks ofVisit 1, and does not agree to stop for the duration of the study.

21. Participation in another clinical study with an IP administered in the last 30 daysor 5 half-lives, whichever is longer.

22. Involvement of any AstraZeneca, Fortrea, or study site employee or their closerelatives.

23. Participants who have previously received HFO via inhalation (eg, BGF [also known asPT010, Breztri, Trixeo] HFO).

24. Judgment by the investigator that the participant should not participate in thestudy if they have any ongoing or recent (ie, during the Screening Period) minormedical complaints that may interfere with the interpretation of study data or areconsidered unlikely to comply with study procedures, restrictions, and requirements.

25. Participants who cannot communicate reliably with the investigator.

26. Vulnerable participants, eg, kept in detention, protected adults under guardianship,trusteeship, or committed to an institution by governmental or judicial order.

27. Female participants who are currently pregnant (confirmed with positive pregnancytest), breast feeding, or planned pregnancy during the study or women ofchildbearing potential not using acceptable contraception measures (see InclusionCriterion).