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PT027 Compared to PT007 in Patients With Asthma With Mannitol-induced Acute Airway Obstruction

Primary Purpose

Asthma

Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
PT027
PT007
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Acute airway obstruction, Albuterol, Budesonide, Short-acting beta2-agonists (SABA), Albuterol Sulfate

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participants who have been diagnosed with asthma > 6 months before Visit 1 by a physician.
  • Participants must have been prescribed and using as-needed SABA as only asthma treatment for at least 4 weeks before screening visit.
  • Participants should have pre-bronchodilator FEV1 ≥ 1.5 L and FEV1 ≥ 60% to < 90% predicted normal at Visit 1.
  • Participants should have a positive response to mannitol challenge performed at Visit 1 (a decrease in FEV1 by at least 15% [PD15] at ≤ 635 mg).
  • Participants should return to within 10% of baseline FEV1, within 1 hour after positive mannitol challenge and 4 inhalations of PT007, performed at Visit 1.
  • Participants should be able to adhere to study procedures in the judgment of the Investigator.
  • Participants who have received COVID-19 vaccination and are considered fully vaccinated by local health authorities definitions at Visit 1.
  • Male or female.
  • Women of childbearing potential must have a negative urine pregnancy test at each study visit.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.
  • Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.

Exclusion Criteria:

  • Any evidence of clinically significant lung disease other than asthma.
  • If the participant has had any face-to-face unscheduled or urgent visit for asthma worsening within the last 4 weeks.
  • Any significant disease or disorder, or evidence of drug/substance abuse which in the Investigator's opinion would pose a risk to participant safety, interfere with the conduct of study, have an impact on the study results, or make it undesirable for the participant to participate in the study.
  • If participants have used Inhaled corticosteroids (ICS) within 1 month prior to enrolment.
  • If they have used immunosuppressive medication (including but not limited to methotrexate, troleandomycin, cyclosporine, azathioprine, systemic corticosteroids including regular treatment with oral corticosteroids or intramuscular long-acting depot corticosteroids, or any experimental anti-inflammatory therapy) within 3 months prior to enrolment.
  • If they have used allergen-specific immunotherapy (desensitization) within 3 months prior to enrolment.
  • If they have used systemic corticosteroids (including oral and injected) within 3 months prior to enrolment.
  • If they have received any marketed or investigational biologic within 4 months or 5 half-lives prior to enrolment (whichever is longer) or received any investigational nonbiologic agent within 30 days or 5 half-lives prior to enrolment (whichever is longer).
  • Participants with a known hypersensitivity to beta2-agonists, ICS, mannitol, or any of the excipients of the product.
  • Any clinically significant abnormal findings in physical examination, vital signs, ECG (eg, participants with QTcF > 500 ms), hematology, clinical chemistry, or urinalysis, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete entire duration of the study.
  • If they are current smokers or participants with smoking history ≥ 10 pack years including the use of vaping products, such as electronic cigarettes, and water pipes. If they are former smokers with a smoking history of <10 pack years, including former vaping or water pipe users, smoking must have stopped for at least 6 months prior to Visit 1 to be eligible.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and its affiliates and/or staff at the study site and their immediate relative(s)).
  • 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.
  • Breast feeding, pregnancy or intention to become pregnant during the course of the study.
  • Previous randomization in the present study.

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment A (PT027) [experimental], then Treatment B (PT007) [active comparator] Part 1 & 2

Treatment B (PT007) [active comparator], then Treatment A (PT027) [experimental] Part 1 & 2

Arm Description

At Visit 2, participants will receive repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge, followed by a washout period of 10-14 days. At Visit 3, participants will receive repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge.

At Visit 2, participants will receive repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge, followed by a washout period of 10 to 14 days. At Visit 3, participants will receive repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge.

Outcomes

Primary Outcome Measures

Change from mannitol baseline Forced expiratory volume in the first second (FEV1) Area under the curve (AUC [0-60 min]) post-mannitol challenge 1
The efficacy of repeated dosing of PT027 relative to PT007, on post-dose lung function, when used by participants with asthma on SABA as-needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.

Secondary Outcome Measures

Change from mannitol baseline in FEV1 AUC (0-15 min) post-mannitol challenge 1
The efficacy of PT027 after a single dose compared with PT007 in reversal of acute airway obstruction, when used by participants with asthma on SABA as-needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.
Change from mannitol baseline in FEV1 at 8 hours post-mannitol challenge 1
The efficacy of PT027 compared with PT007 in the sustainability of effect of reversal of acute airway obstruction post-mannitol challenge 1 in participants with asthma on SABA as needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.
Time to return to baseline (-30 min) FEV1 post-mannitol challenge 2, pre-final dose of rescue/reliever
The efficacy of a single dose of PT027 compared with PT007 on post-dose speed of recovery of lung function following a recurring trigger of acute airway obstruction induced by mannitol challenges in participants with asthma on SABA as needed treatment only will be assessed.
Peak fall in FEV1 from baseline (-30 min) FEV1 to post-mannitol challenge 2, pre-final dose of rescue/reliever
The protective efficacy of prior repetitive doses of PT027 compared with PT007 on lung function fall in response to a recurring trigger of acute airway obstruction induced by mannitol challenges in participants with asthma on SABA as-needed treatment only will be assessed.
Peak fall in FEV1 from 8 hours to post-mannitol challenge 2, pre-final dose of rescue/reliever
The protective efficacy of prior repetitive doses of PT027 compared with PT007 on lung function fall in response to a recurring trigger of acute airway obstruction in participants with asthma on SABA as-needed treatment only will be assessed.
Number of participants with Adverse Events (AEs)
The safety and tolerability of repeated dosing of PT027 as compared to PT007 in participants with asthma on SABA as-needed treatment only will be assessed.

Full Information

First Posted
August 25, 2022
Last Updated
October 5, 2023
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05555290
Brief Title
PT027 Compared to PT007 in Patients With Asthma With Mannitol-induced Acute Airway Obstruction
Official Title
ALTA - ALbuterol/Budesonide Treatment in Acute Airway Obstruction. A Randomized, Double-blind, 2-period, Cross-over Study Evaluating Efficacy and Safety of Repeated Doses of PT027 Compared to PT007 in Patients With Asthma and Acute Airway Obstruction Induced by Repeated Mannitol Challenges
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 28, 2022 (Actual)
Primary Completion Date
January 11, 2024 (Anticipated)
Study Completion Date
January 11, 2024 (Anticipated)

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 evaluating efficacy and safety of repeated doses of PT027 compared to PT007 in patients with asthma and acute airway obstruction induced by repeated mannitol challenges
Detailed Description
This is a multi-center, randomized, double-blind, 2-period, cross-over study evaluating efficacy and safety of repeated doses of PT027 (albuterol/budesonide pressurized metered dose inhaler (pMDI)) compared to PT007 (albuterol pMDI) in participants with asthma and acute airway obstruction induced by 2 mannitol challenges at least 8 hours apart. It is a two-part study where Part 1 will enroll a small cohort of participants and will be used as a pilot study. The data obtained from Part 1 will be assessed by an internal AstraZeneca advisory board, and suggested changes may be made to Part 2 of the study. The following is the sequence of study visits: (i) Visit 1 (V1) screening (ii) Visit 2 (V2) 10 to 14 days after Visit 1 assessments; 1st dual challenge and treatment visit (iii) Visit 3 (V3) 10 to 14 days after Visit 2; 2nd dual challenge and treatment visit At Visit 1, all participants will be subjected to a single mannitol challenge to establish a positive response (defined as a ≥15% decrease in forced expiratory volume in the first second [FEV1] from the 0 mg mannitol FEV1 value) and will receive 4 puffs of open-label PT007. At Visit 2, participants will be randomized to one of 2 treatment sequences, A/B or B/A, where treatments A and B are defined as: (i) Treatment A = PT027 (ii) Treatment B = PT007 For treatment sequence A/B, participants will receive repeated inhalations of PT027 at Visit 2 followed by repeated inhalations of PT007 in Visit 3 . For treatment sequence B/A, participants will receive repeated inhalations of PT007 at Visit 2 followed by repeated inhalations of PT027 in Visit 3. Participants will have a Follow-up Telephone call 7 days after Visit 3/after Early discontinuation (ED).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Acute airway obstruction, Albuterol, Budesonide, Short-acting beta2-agonists (SABA), Albuterol Sulfate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
The study will enroll 17 participants in Part 1 and 88 participants in Part 2
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
105 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment A (PT027) [experimental], then Treatment B (PT007) [active comparator] Part 1 & 2
Arm Type
Experimental
Arm Description
At Visit 2, participants will receive repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge, followed by a washout period of 10-14 days. At Visit 3, participants will receive repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge.
Arm Title
Treatment B (PT007) [active comparator], then Treatment A (PT027) [experimental] Part 1 & 2
Arm Type
Experimental
Arm Description
At Visit 2, participants will receive repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge, followed by a washout period of 10 to 14 days. At Visit 3, participants will receive repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge.
Intervention Type
Combination Product
Intervention Name(s)
PT027
Intervention Description
When administered PT027, participants will receive 2 actuations of albuterol- budesonide per dose administered as oral inhalations.
Intervention Type
Combination Product
Intervention Name(s)
PT007
Intervention Description
When administered PT007, participants will receive 2 actuations of albuterol administered as oral inhalations.
Primary Outcome Measure Information:
Title
Change from mannitol baseline Forced expiratory volume in the first second (FEV1) Area under the curve (AUC [0-60 min]) post-mannitol challenge 1
Description
The efficacy of repeated dosing of PT027 relative to PT007, on post-dose lung function, when used by participants with asthma on SABA as-needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.
Time Frame
Up to 60 minutes post mannitol challenge 1
Secondary Outcome Measure Information:
Title
Change from mannitol baseline in FEV1 AUC (0-15 min) post-mannitol challenge 1
Description
The efficacy of PT027 after a single dose compared with PT007 in reversal of acute airway obstruction, when used by participants with asthma on SABA as-needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.
Time Frame
Up to 15 minutes post mannitol challenge 1
Title
Change from mannitol baseline in FEV1 at 8 hours post-mannitol challenge 1
Description
The efficacy of PT027 compared with PT007 in the sustainability of effect of reversal of acute airway obstruction post-mannitol challenge 1 in participants with asthma on SABA as needed treatment only who are experiencing acute airway obstruction induced by mannitol challenges will be assessed.
Time Frame
At 8 hours (480 minutes) post mannitol challenge 1
Title
Time to return to baseline (-30 min) FEV1 post-mannitol challenge 2, pre-final dose of rescue/reliever
Description
The efficacy of a single dose of PT027 compared with PT007 on post-dose speed of recovery of lung function following a recurring trigger of acute airway obstruction induced by mannitol challenges in participants with asthma on SABA as needed treatment only will be assessed.
Time Frame
Up to 60 minutes post-mannitol challenge 2
Title
Peak fall in FEV1 from baseline (-30 min) FEV1 to post-mannitol challenge 2, pre-final dose of rescue/reliever
Description
The protective efficacy of prior repetitive doses of PT027 compared with PT007 on lung function fall in response to a recurring trigger of acute airway obstruction induced by mannitol challenges in participants with asthma on SABA as-needed treatment only will be assessed.
Time Frame
At approximately 490 minutes post mannitol challenge 1
Title
Peak fall in FEV1 from 8 hours to post-mannitol challenge 2, pre-final dose of rescue/reliever
Description
The protective efficacy of prior repetitive doses of PT027 compared with PT007 on lung function fall in response to a recurring trigger of acute airway obstruction in participants with asthma on SABA as-needed treatment only will be assessed.
Time Frame
To post-mannitol challenge 2 at approximately 490 minutes
Title
Number of participants with Adverse Events (AEs)
Description
The safety and tolerability of repeated dosing of PT027 as compared to PT007 in participants with asthma on SABA as-needed treatment only will be assessed.
Time Frame
From Screening Visit (approximately 5 hours) until the Follow up telephone call (7 days after the last treatment visit)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants who have been diagnosed with asthma > 6 months before Visit 1 by a physician. Participants must have been prescribed and using as-needed SABA as only asthma treatment for at least 4 weeks before screening visit. Participants should have pre-bronchodilator FEV1 ≥ 1.5 L and FEV1 ≥ 60% to < 90% predicted normal at Visit 1. Participants should have a positive response to mannitol challenge performed at Visit 1 (a decrease in FEV1 by at least 15% [PD15] at ≤ 635 mg). Participants should return to within 10% of baseline FEV1 (≥ 90% of baseline FEV1), within 1 hour after positive mannitol challenge and 4 inhalations of PT007, performed at Visit 1. Participants should be able to adhere to study procedures in the judgment of the Investigator. Male or female. Women of childbearing potential must have a negative urine pregnancy test at each study visit. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative. Exclusion Criteria: Any evidence of clinically significant lung disease other than asthma. If the participant has had any face-to-face unscheduled or urgent visit for asthma worsening within the last 4 weeks. Any significant disease or disorder, or evidence of drug/substance abuse which in the Investigator's opinion would pose a risk to participant safety, interfere with the conduct of study, have an impact on the study results, or make it undesirable for the participant to participate in the study. If participants have used Inhaled corticosteroids (ICS) within 1 month prior to enrolment. If they have used immunosuppressive medication (including but not limited to methotrexate, troleandomycin, cyclosporine, azathioprine, systemic corticosteroids including regular treatment with oral corticosteroids or intramuscular long-acting depot corticosteroids, or any experimental anti-inflammatory therapy) within 3 months prior to enrolment (Visit 1) or plan on starting immunosuppressive medications during the study. If they have used allergen-specific immunotherapy (desensitization) within 3 months prior to enrolment. If they have used systemic corticosteroids (including oral and injected) within 3 months prior to enrolment. If they have received any marketed or investigational biologic within 4 months or 5 half-lives prior to enrolment (whichever is longer) or received any investigational nonbiologic agent within 30 days or 5 half-lives prior to enrolment (whichever is longer). Participants with a known hypersensitivity to beta2-agonists, ICS, mannitol, or any of the excipients of the product. Any clinically significant abnormal findings in physical examination, vital signs, ECG (eg, participants with QTcF > 500 ms), hematology, clinical chemistry, or urinalysis, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete entire duration of the study. If they are current smokers or participants with smoking history ≥ 10 pack years including the use of vaping products, such as electronic cigarettes, and water pipes. If they are former smokers with a smoking history of <10 pack years, including former vaping or water pipe users, smoking must have stopped for at least 6 months prior to Visit 1 to be eligible. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and its affiliates and/or staff at the study site and their immediate relative(s)). 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. Breast feeding, pregnancy or intention to become pregnant during the course of the study. Previous randomization in the present study.
Facility Information:
Facility Name
Research Site
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21046
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

PT027 Compared to PT007 in Patients With Asthma With Mannitol-induced Acute Airway Obstruction

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