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Study to Assess Bronchospasm Potentially Induced by HFO vs HFA MDI in Participants With Well/Partially Controlled Asthma

Primary Purpose

Asthma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
HFA MDI
HFO MDI
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Asthma, Bronchospasm

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception. Contraceptive subdermal implant Intrauterine device or intrauterine system Oral contraceptive (combined or progesterone only) Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel's review of participant's medical records, medical examination and/or semen analysis or medical history interview provided by her or her partner. Bilateral tubal ligation Informed Consent 8 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion Criteria: 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. Other Exclusions 14 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 15 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 16 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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Treatment A: HFO propellant only MDI

Treatment B: HFA propellant only MDI

Arm Description

Test arm, 4 inhalations per dose

Reference arm, 4 inhalations per dose

Outcomes

Primary Outcome Measures

Change from baseline FEV1 to 15-min post-dose
To assess the potential change in FEV1 induced by HFO MDI as compared with HFA MDI in participants with asthma

Secondary Outcome Measures

Cumulative incidence of bronchospasm events
To assess the potential of bronchospasm induced by HFO MDI as compared with HFA MDI in participants with asthma
Safety and tolerability will be evaluated in terms of AEs
To assess the safety and tolerability of HFO MDI as compared with HFA MDI in participants with asthma

Full Information

First Posted
April 28, 2023
Last Updated
September 26, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05850494
Brief Title
Study to Assess Bronchospasm Potentially Induced by HFO vs HFA MDI in Participants With Well/Partially Controlled Asthma
Official Title
Randomized, DB, Crossover Study to Assess Bronchospasm Potentially Induced by HFO MDI vs. HFA MDI Propellant in Participants With Asthma Well/Partially Controlled on SABA With or Without Low-Dose ICS
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 2, 2023 (Actual)
Primary Completion Date
August 21, 2023 (Actual)
Study Completion Date
August 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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
Detailed Description
This is a phase 3b, multicentre, randomized, double-blind, single-dose crossover study comparing the safety and tolerability of HFO MDI with HFA MDI delivered in participants with well controlled or partially controlled asthma defined as an ACQ-5 score < 1.5.Eligible participants are at least 18 years of age and no older than 45 years of age and are required to have asthma as defined by GINA guidelines (GINA 2022). Participants are required to be 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. The primary objective is to assess the potential change in FEV1 induced by HFO MDI as compared with HFA MDI in participants with asthma. This study will be conducted at approximately 5 sites in the US and will randomize approximately 52 adult participants to achieve 46 completers. The study will be conducted for a maximal 37 days and will comprise: A screening period approximately 14 (±2) days prior to first dosing Two treatment periods of 1 day each, with a 3 to 12-day washout period between the 2 treatment periods A final safety follow-up visit via telephone contact 3 to 7 days after the final dose administration in Treatment Period 2 Single dose study treatment will be administered via MDI device as 4 inhalations: Treatment A: HFO propellant only MDI; 4 inhalations per dose - test formulation Treatment B: HFA propellant only MDI; 4 inhalations per dose - reference formulation

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Asthma, Bronchospasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment A: HFO propellant only MDI
Arm Type
Experimental
Arm Description
Test arm, 4 inhalations per dose
Arm Title
Treatment B: HFA propellant only MDI
Arm Type
Active Comparator
Arm Description
Reference arm, 4 inhalations per dose
Intervention Type
Drug
Intervention Name(s)
HFA MDI
Other Intervention Name(s)
Propellant in MDI
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
HFO MDI
Other Intervention Name(s)
Propellant in MDI
Intervention Description
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
Primary Outcome Measure Information:
Title
Change from baseline FEV1 to 15-min post-dose
Description
To assess the potential change in FEV1 induced by HFO MDI as compared with HFA MDI in participants with asthma
Time Frame
up to 36 days
Secondary Outcome Measure Information:
Title
Cumulative incidence of bronchospasm events
Description
To assess the potential of bronchospasm induced by HFO MDI as compared with HFA MDI in participants with asthma
Time Frame
up to 36 days
Title
Safety and tolerability will be evaluated in terms of AEs
Description
To assess the safety and tolerability of HFO MDI as compared with HFA MDI in participants with asthma
Time Frame
up to 36 days
Other Pre-specified Outcome Measures:
Title
Repeated measurements of change from baseline in FEV1 at 5, 15, and 30 minutes post-dose during each treatment period
Description
To compare the FEV1 measurements between HFO MDI versus HFA MDI in participants with asthma
Time Frame
up to 36 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception. Contraceptive subdermal implant Intrauterine device or intrauterine system Oral contraceptive (combined or progesterone only) Injectable progestogen Contraceptive vaginal ring Percutaneous contraceptive patches Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study, and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel's review of participant's medical records, medical examination and/or semen analysis or medical history interview provided by her or her partner. Bilateral tubal ligation Informed Consent 8 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion Criteria: 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. Other Exclusions 14 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 15 Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 16 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Miller, MD
Organizational Affiliation
Northeast Medical Research Associates, Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Craig LaForce, MD
Organizational Affiliation
North Carolina Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Allen T Funkhouser, MC
Organizational Affiliation
EPIMRD Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeffrey Tillinghast, MD
Organizational Affiliation
The Clinical Research Center, LLC.
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
North Dartmouth
State/Province
Massachusetts
ZIP/Postal Code
02747
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Research Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Research Site
City
El Paso
State/Province
Texas
ZIP/Postal Code
79903
Country
United States

12. IPD Sharing Statement

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Results Reference
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Citation
Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2022. http://ginasthma.org.
Results Reference
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PubMed Identifier
31613151
Citation
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.
Results Reference
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Citation
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.
Results Reference
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PubMed Identifier
16226443
Citation
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.
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Study to Assess Bronchospasm Potentially Induced by HFO vs HFA MDI in Participants With Well/Partially Controlled Asthma

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