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

September 26, 2023 updated by: AstraZeneca

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • North Dartmouth, Massachusetts, United States, 02747
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63141
        • Research Site
    • North Carolina
      • Raleigh, North Carolina, United States, 27607
        • Research Site
    • Texas
      • El Paso, Texas, United States, 79903
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age

    1. 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

    2. Participants who have a documented history of physician-diagnosed asthma

      ≥ 12 months prior to Visit 1, according to GINA guidelines (GINA 2022).

    3. 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.
    4. ACQ-5 total score < 1.5 at Visit 1.
    5. A pre-bronchodilator FEV1 > 60% predicted normal value at Visit 1.

    6. Demonstrate acceptable MDI administration technique.

      Sex and Contraceptive/Barrier Requirements

    7. 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

    1. 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).
    2. 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).
    3. 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.
    4. 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.
    5. Hospitalization for asthma within 1 year prior to Visit 1.
    6. Admission to intensive care unit or mechanical ventilation due to asthma exacerbation.

    7. Known history of drug or alcohol abuse within 12 months of Visit 1.

      Prior/Concomitant Therapy

    8. 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).
    9. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment A: HFO propellant only MDI
Test arm, 4 inhalations per dose
Drug: HFO MDI
  • 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
Other Names:
  • Propellant in MDI
Active Comparator: Treatment B: HFA propellant only MDI
Reference arm, 4 inhalations per dose
Drug: HFA MDI
  • 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
Other Names:
  • Propellant in MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline FEV1 to 15-min post-dose
Time Frame: up to 36 days
To assess the potential change in FEV1 induced by HFO MDI as compared with HFA MDI in participants with asthma
up to 36 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of bronchospasm events
Time Frame: up to 36 days
To assess the potential of bronchospasm induced by HFO MDI as compared with HFA MDI in participants with asthma
up to 36 days
Safety and tolerability will be evaluated in terms of AEs
Time Frame: up to 36 days
To assess the safety and tolerability of HFO MDI as compared with HFA MDI in participants with asthma
up to 36 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Repeated measurements of change from baseline in FEV1 at 5, 15, and 30 minutes post-dose during each treatment period
Time Frame: up to 36 days
To compare the FEV1 measurements between HFO MDI versus HFA MDI in participants with asthma
up to 36 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Craig LaForce, MD, North Carolina Clinical Research
  • Principal Investigator: David Miller, MD, Northeast Medical Research Associates, Inc.
  • Principal Investigator: Allen T Funkhouser, MC, EPIMRD Inc.
  • Principal Investigator: Jeffrey Tillinghast, MD, The Clinical Research Center, LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2023

Primary Completion (Actual)

August 21, 2023

Study Completion (Actual)

August 21, 2023

Study Registration Dates

First Submitted

April 28, 2023

First Submitted That Met QC Criteria

April 28, 2023

First Posted (Actual)

May 9, 2023

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D5985C00007

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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