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

NCT05755932 | Completed Phase 3 FDA Drug

• 1 other identifier: D5985C00006
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 5

Brief Summary

A Study to Assess the Effect of the HFO MDI Propellant on Mucociliary Clearance Compared to the HFA MDI Propellant in Healthy Participants

Conditions

Mucociliary Clearance

Keywords

Mucociliary Clearance, Propellant

Outcome Measures

Primary Outcomes (1)

• Change from baseline in MCC through 60 minutes following inhalation of 99m technetium-labelled colloid (sulfur or albumin) colloid and gamma camera imaging.

  Change from baseline in MCC through 60 minutes, following inhalation of 99m technetium-labelled colloid (sulfur or albumin) and gamma camera imaging

  7 days

Secondary Outcomes (1)

• Change from baseline in MCC at 3 hours following inhalation of 99m technetium-labelled colloid (sulfur or albumin)and gamma camera imaging

  7 days

Other Outcomes (1)

• Safety and tolerability will be evaluated in terms of AEs

  up to 35 days

Study Arms (2)

Treatment A: HFO MDI

EXPERIMENTAL

Test arm, 6 inhalations BID for 7 days

Drug: HFO-1234ze(E)

Treatment B: HFA MDI

ACTIVE COMPARATOR

Reference arm, 6 inhalations BID for 7 days

Drug: HFA-134a

Interventions

HFO-1234ze(E) DRUG

* Dose formulation: metered dose inhaler (MDI) * Unit dose strength(s): Experimental (propellant only) * Dosage level(s): 6 inhalations, BID * Route of administration: Oral inhalation * Participants will receive treatment A in 1 of 2 possible treatment sequences: AB or BA

Also known as: Propellant in MDI

Treatment A: HFO MDI

HFA-134a DRUG

* Dose formulation: metered dose inhaler (MDI) * Unit dose strength(s): Reference (propellant only) * Dosage level(s): 6 inhalations, BID * Route of administration: Oral inhalation * Participants will receive treatment B in 1 of 2 possible treatment sequences: AB or BA.

Also known as: Propellant in MDI

Treatment B: HFA MDI

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Healthy non-smoking male and/or female participants aged 18 to 60 years inclusive at the time of signing the informed consent, without respiratory comorbidities.
• Participant must have a forced expiratory volume in 1 second (FEV1) ≥ 80% of the predicted value for age, height, and ethnicity at screening, and FEV1/forced vital capacity (FVC) ratio of \> 70%.
• Participant must demonstrate acceptable MDI administration using empty training MDI.
• Participant willing to comply with study IP administration requirements, defined as ≥ 80% participant medication adherence during the Treatment Periods.
• Body mass index (BMI) within the range 18 to 35 kg/m2 (inclusive), and weight within the range 50 to 120 kg (inclusive).
• Female participants must be not of childbearing potential or must use a form of highly effective birth control as defined below:
• (a) Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:
• Women \< 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Women ≥ 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
• Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. At enrollment, women of childbearing potential who are sexually active with a non-sterilized male partner should be stable on their chosen method of highly effective birth control, as defined below, and willing to remain on the birth control until at least 14 days after last dose of study intervention. Cessation of contraception 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 not acceptable methods of contraception. Female condom and male condom should not be used together.
• All women of childbearing potential must have a negative serum pregnancy test result at Visit 1.
• Females \<50 years of age with amenorrhea for 12 months without an alternative medical cause must have a serum FSH test at Visit 1.
• Highly effective birth control methods are listed below:

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• History of smoking \> 10 pack-years, or participant quit smoking \< 6 months prior to screening.
• Acute or chronic upper or lower respiratory illness within 30 days of screening.
• Respiratory medication or medication impacting ciliary clearance for any indication within 30 days of screening.
• History of more than 2 chest CTs or equivalent (\> 10 mSv) within the past year.
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of the IP.
• History of any cancer except squamous cell and basal cell carcinomas of the skin.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at screening as judged by the investigator.
• Any clinically significant abnormal findings in vital signs at screening, as judged by the investigator.
• Any clinically significant abnormalities on 12-lead ECG at screening, as judged by the investigator. Note: Participants with ECG QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 480 msec will be excluded.
• A SARS-CoV-2 infection in the 8 weeks prior to Visit 1, or during the Screening Period, or that required hospitalization at any time prior to Visit 1 or during the Screening Period.
• Participant has clinical signs and symptoms consistent with SARS-CoV-2 infection; eg, fever, dry cough, dyspnea, sore throat, fatigue, or laboratory-confirmed acute infection with SARS-CoV-2.
• Participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated, Intensive Care Unit stay).
• History of any respiratory disorders such as asthma, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis, alpha-1 antitrypsin, primary ciliary dyskinesia, cystic fibrosis.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Kansas City, Kansas, 66160, United States

Location

Research Site

Baltimore, Maryland, 21287, United States

Location

Research Site

Chapel Hill, North Carolina, 27599, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15213, United States

Location

Research Site

Glasgow, G4 0SF, United Kingdom

Location

Related Links

• CSR Synopsis

MeSH Terms

Interventions

norflurane

Study Officials

• William D Bennett, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Andreas Schmid, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

• Timothy Corcoran, PhD

  UPMC Montefiore Hospital

  PRINCIPAL INVESTIGATOR

• Peter Mogayzel, MD, PhD, MBA

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Douglas Conrad, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study is double blinded with regard to treatment (MDI administered with 2 different propellants \[Treatment A or B\]), ie, the sponsor, the investigator, all clinical staff involved in the clinical study, the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, double-blind, multi-site, two-way crossover study to assess the effect on MCC and safety of HFO propellant compared to HFA propellant in healthy participants. Mucociliary clearance will be determined after 1 week of twice daily (BID) administration of HFO MDI (test) and HFA MDI (reference). Study treatment will be administered via MDI device as 6 inhalations BID Participants will receive treatments in 1 of 2 possible treatment sequences: A followed by B, or B followed by A. * Treatment A: HFO MDI - test formulation * Treatment B: HFA MDI - reference formulation The study will comprise * A Screening Period 7 to 14 days prior to first dosing; * Two Treatment Periods (TPs) of 7 days each, a 7 to 14 day Washout Period between the 2 TPs; and * A final safety Follow-up Visit

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 6, 2023
• Study Start: June 14, 2023
• Primary Completion: July 22, 2024
• Study Completion: July 22, 2024
• Last Updated: February 25, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (4)