Study to Assess Bronchospasm Potentially Induced by Next-Generation Propellant vs HFA Propellant in an MDI in Participants With Well/Partially Controlled Asthma

NCT05850494 | Completed Phase 3 Results FDA Drug

• 1 other identifier: D5985C00007
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 4

Brief Summary

A study to assess bronchospasm potentially induced by HFO MDI as compared with HFA MDI in participants with well controlled or partially controlled asthma

Conditions

Asthma

Keywords

Asthma, Bronchospasm

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Normalized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 15 Minutes (AUC0-15 Min) Post-dose

  The change from baseline (30 minutes pre-dose) in normalized FEV1 AUC0-15 min postdose induced by Treatment HFO was compared with Treatment HFA.

  30 minutes prior to dosing and at 5, 15, and 30 minutes post-dose

Secondary Outcomes (2)

• Number of Participants With Bronchospasm Events

  30 minutes prior to dosing and at 5 and 15 minutes post-dose

• Safety and Tolerability Evaluated in Terms of Adverse Events (AEs)

  From screening (Day - 14) to the last dose (day 8) + 7 days

Study Arms (2)

Treatment A: HFO propellant only MDI

EXPERIMENTAL

Test arm, 4 inhalations per dose

Drug: HFO MDI

Treatment B: HFA propellant only MDI

ACTIVE COMPARATOR

Reference arm, 4 inhalations per dose

Drug: HFA MDI

Interventions

HFO MDI DRUG

* Dose formulation: MDI * Unit dose strength(s): Experimental (propellant only) * Dosage Level: 4 inhalations, single dose * Route of administration: Oral inhalation * Participants will receive treatment A in 1 or 2 possible sequences AB or BA

Also known as: Propellant in MDI

Treatment A: HFO propellant only MDI

HFA MDI DRUG

* Dose formulation: MDI * Unit dose strength(s): Reference (propellant only) * Dosage Level: 4 inhalations, single dose * Route of administration: Oral inhalation * Participants will receive treatment A in 1 or 2 possible sequences AB or BA

Also known as: Propellant in MDI

Treatment B: HFA propellant only MDI

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age
• Male and female participant must be 18 to 45 years of age inclusive, at the time of signing the informed consent form (ICF).
• Type of Participant and Disease Characteristics
• Participants who have a documented history of physician-diagnosed asthma
• ≥ 12 months prior to Visit 1, according to GINA guidelines (GINA 2022).
• Participants who are well controlled or partially controlled on their current treatment for asthma, including, low-dose ICS daily or low-dose ICS/formoterol as needed (not approved in the US), or SABA as needed, or low-dose ICS whenever SABA as needed is used (low-dose ICS as defined by GINA 2022 in Table 4), for 4 weeks prior to screening.
• ACQ-5 total score \< 1.5 at Visit 1.
• A pre-bronchodilator FEV1 \> 60% predicted normal value at Visit 1.
• Demonstrate acceptable MDI administration technique.
• Sex and Contraceptive/Barrier Requirements
• Females must be not of childbearing potential, or should be using a form of highly effective birth control as defined below:
• Female participants 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 included in this study will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the postmenopausal range.
• 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 enrolment, 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 amenorrhoea 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.
• Highly effective birth control methods are listed below:

You may not qualify if:

• Medical Conditions
• Life-threatening asthma defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).
• Current smokers, former smokers with \> 10 pack-years history, or former smokers who stopped smoking \< 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
• Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (e.g., active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, COPD, and uncontrolled severe asthma). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the participant at risk through participation, or that could affect the safety/tolerability analysis.
• Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the screening period.
• Hospitalization for asthma within 1 year prior to Visit 1.
• Admission to intensive care unit or mechanical ventilation due to asthma exacerbation.
• Known history of drug or alcohol abuse within 12 months of Visit 1.
• Prior/Concomitant Therapy
• Do not meet the stable dosing period prior to Visit 1 (see Table 5) or unable to abstain from protocol-defined prohibited medications during screening and treatment periods (see Table 6 and Table 7).
• Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, e.g., vector, lipid nanoparticle) ≤ 7 days prior to Visit 1 (from last vaccination or booster dose).
• Prior/Concurrent Clinical Study Experience 10 Participation in another clinical study with an investigational product administered within 30 days or 5 half-lives (whichever is longer). 11 Participants with a known hypersensitivity to HFO or HFA or any of the excipients of the product. 12 Previously randomized into a study with an HFO-containing MDI.
• Diagnostic Assessments 13 Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis, vital signs, or electrocardiogram (ECG), which in the opinion of the investigator, may put the participant at risk because of his/her participation in the study. Note: Participants with ECG QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 480 msec will be excluded. Participants with high degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker will also be excluded.
• Previous enrolment or randomisation in the present study. 17 For women only - currently pregnant (confirmed with positive pregnancy test), breast feeding, or planned pregnancy during the study or women of childbearing potential not using acceptable contraception measures. 18 Study investigators, sub-investigators, coordinators, and their employees or immediate family members.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

North Dartmouth, Massachusetts, 02747, United States

Location

Research Site

St Louis, Missouri, 63141, United States

Location

Research Site

Raleigh, North Carolina, 27607, United States

Location

Research Site

El Paso, Texas, 79903, United States

Location

Related Publications (10)

• Buhl R, Tanase AM, Hosoe M, Cao W, Demin I, Bartels C, Jauernig J, Ziegler D, Patalano F, Hederer B, Kanniess F, Tillmann HC. A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler(R) or Twisthaler(R) in patients with asthma. Pulm Pharmacol Ther. 2020 Jun;62:101919. doi: 10.1016/j.pupt.2020.101919. Epub 2020 May 7.

  PMID: 32387408 RESULT

• Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2022. http://ginasthma.org.

  RESULT

• Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE, Rosenfeld M, Stanojevic S, Swanney MP, Thompson BR. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70-e88. doi: 10.1164/rccm.201908-1590ST.

  PMID: 31613151 RESULT

• Investigator's Brochure - Budesonide, Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (BGF MDI); Budesonide and Formoterol Fumarate Inhalation Aerosol (BFF MDI); Budesonide Inhalation Aerosol (BD MDI); Glycopyrronium Inhalation Aerosol (GP MDI) (Also known as PT010 [BGF MDI], PT009 [BFF MDI], PT008 (BD MDI); PT001 (GP MDI); Edition Number 9.0, 16 September 2022.

  RESULT

• Juniper EF, Bousquet J, Abetz L, Bateman ED; GOAL Committee. Identifying 'well-controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. Respir Med. 2006 Apr;100(4):616-21. doi: 10.1016/j.rmed.2005.08.012. Epub 2005 Oct 13.

  PMID: 16226443 RESULT

• Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999 Oct;14(4):902-7. doi: 10.1034/j.1399-3003.1999.14d29.x.

  PMID: 10573240 RESULT

• Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.

  PMID: 16055882 RESULT

• Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.

  PMID: 22743675 RESULT

• Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993 Mar;16:5-40. No abstract available.

  PMID: 8499054 RESULT

• Pleasants RA, Bell AS, Jassal M, Xu J, Petullo D, Raphiou I, Aurivillius M, Bondarov P, Patel M. A Randomized, Double-Blind Crossover Study of Change in Post-Dose Lung Function with Hydrofluoroolefin-1234ze, a Next-Generation Propellant for Metered Dose Inhalers, in Participants with Asthma. J Aerosol Med Pulm Drug Deliv. 2025 Oct;38(5):275-283. doi: 10.1089/jamp.2024.0061. Epub 2025 Jun 24.

  PMID: 40551410 DERIVED

Related Links

• Redacted CSR synopsis

MeSH Terms

Conditions

Asthma; Bronchial Spasm

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• David Miller, MD

  Northeast Medical Research Associates, Inc.

  PRINCIPAL INVESTIGATOR

• Craig LaForce, MD

  North Carolina Clinical Research

  PRINCIPAL INVESTIGATOR

• Allen T Funkhouser, MC

  EPIMRD Inc.

  PRINCIPAL INVESTIGATOR

• Jeffrey Tillinghast, MD

  The Clinical Research Center, LLC.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The purpose of this study is to assess bronchospasm potentially induced by hydrofluoroolefin (HFO) metered dose inhaler (MDI) as compared with hydrofluoroalkane (HFA) MDI in participants with asthma, well controlled or partially controlled on treatment for asthma, including, low-dose inhaled corticosteroid (ICS) daily or low-dose ICS/formoterol as needed (not approved in the US), or short-acting beta2-agonists (SABA) as needed, or low-dose ICS whenever SABA as needed is used. Study details include: * The study duration will be up to 37 days. * The treatment duration will be 1 day for each treatment period. * The visit frequency will be approximately every 1 week.

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 9, 2023
• Study Start: May 2, 2023
• Primary Completion: August 21, 2023
• Study Completion: August 21, 2023
• Last Updated: February 6, 2026
• Results First Posted: July 30, 2025

Record last verified: 2025-11

Locations

US (4)