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Completed

NCT Number: NCT05555290

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

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

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Key information

Conditions

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

Age range

18 year–130 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site

Columbia, Maryland, 21046, United States

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PT027

Combination Product

When administered PT027, participants will receive 2 actuations of albuterol- budesonide per dose administered as oral inhalations.

PT007

Combination Product

When administered PT007, participants will receive 2 actuations of albuterol administered as oral inhalations.

Primary outcomes

  1. Part 1: Change From Mannitol Baseline Forced Expiratory Volume in the First Second (FEV1) Area Under the Curve (AUC [0-60 Min]) Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: Up to 60 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The primary efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on treatment estimand in the Per Protocol (PP) analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  2. Part 1: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: Up to 60 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the randomized set (RS). Superiority was concluded if the 2-sided p-value was < 0.05.

  3. Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: Up to 60 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The primary efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  4. Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: Up to 60 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the modified randomized set (mRS). Superiority was concluded if the 2-sided p-value was < 0.05.

Secondary outcomes

  1. Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: Up to 15 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  2. Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: Up to 15 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the RS. Superiority was concluded if the 2-sided p-value was < 0.05.

  3. Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: Up to 15 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  4. Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: Up to 15 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the mRS. Superiority was concluded if the 2-sided p-value was < 0.05.

  5. Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: At 7 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol is observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  6. Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: At 7 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the RS. Superiority was concluded if the 2-sided p-value was < 0.05.

  7. Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Non-Inferiority Analysis

    Time frame: At 480 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  8. Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Superiority Analysis

    Time frame: At 480 minutes 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 was assessed.

    Mannitol baseline was defined as the FEV1 result where a positive response to mannitol was observed prior to dosing of study drug for challenge 1 in Visit 2 and in Visit 3 (time 0). A positive response was defined as a ≥ 15% decrease from the FEV1 determined after the 0 mg mannitol dose up to ≤ 635 mg cumulative mannitol dose.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the mRS. Superiority was concluded if the 2-sided p-value was < 0.05.

  9. Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Non-Inferiority Analysis

    Time frame: From baseline (30 minutes prior to mannitol challenge 1) up to 60 minutes post-mannitol challenge 2 (up to 550 minutes post-mannitol challenge 1)

    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 was assessed.

    The time to return in minutes was calculated as the time it took for a participant to return to within 5% of the baseline (- 30 min) FEV1 value, post-mannitol challenge 2.

    FEV1 baseline is defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of 3.5 min.

  10. Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Superiority Analysis

    Time frame: From baseline (30 minutes prior to mannitol challenge 1) up to 60 minutes post-mannitol challenge 2 (up to 550 minutes post-mannitol challenge 1)

    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 was assessed.

    The time to return in minutes was calculated as the time it took for a participant to return to within 5% of the baseline (- 30 min) FEV1 value, post-mannitol challenge 2.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the RS. Superiority was concluded if the 2-sided p-value was < 0.05.

  11. Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Non-Inferiority Analysis

    Time frame: From baseline (30 minutes prior to mannitol challenge 1) up to 60 minutes post-mannitol challenge 2 (up to 550 minutes post-mannitol challenge 1)

    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 was assessed.

    The time to return in minutes was calculated as the time it took for a participant to return to within 5% of the baseline (- 30 min) FEV1 value, post-mannitol challenge 2.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the modified per protocol (mPP) analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of 3.5 min.

  12. Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis

    Time frame: From baseline (30 minutes prior to mannitol challenge 1) up to 60 minutes post-mannitol challenge 2 (up to 550 minutes post-mannitol challenge 1)

    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 was assessed.

    The time to return in minutes was calculated as the time it took for a participant to return to within 5% of the baseline (- 30 min) FEV1 value, post-mannitol challenge 2.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the mRS. Superiority was concluded if the 2-sided p-value was < 0.05.

  13. Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis

    Time frame: Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    FEV1 at post-mannitol challenge 2 was the FEV1 result recorded at the end of mannitol challenge 2, i.e. before study intervention treatment, was expected to be at ~490 mins following the mannitol challenge 1.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the mPP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  14. Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis

    Time frame: Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    FEV1 at post-mannitol challenge 2 was the FEV1 result recorded at the end of mannitol challenge 2, i.e. before study intervention treatment, was expected to be at ~490 mins following the mannitol challenge 1.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the RS. Superiority was concluded if the 2-sided p-value was < 0.05.

  15. Part 2: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Non-Inferiority Analysis

    Time frame: Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    FEV1 at post-mannitol challenge 2 was the FEV1 result recorded at the end of mannitol challenge 2, i.e. before study intervention treatment, was expected to be at ~490 mins following the mannitol challenge 1.

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the mPP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  16. Part 2: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis

    Time frame: Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the acceptable efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    FEV1 at post-mannitol challenge 2 was the FEV1 result recorded at the end of mannitol challenge 2, i.e. before study intervention treatment, was expected to be at ~490 mins following the mannitol challenge 1.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the mRS. Superiority was concluded if the 2-sided p-value was < 0.05.

  17. Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis

    Time frame: 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    The peak fall in FEV1 (in mL) was derived as: FEV1 at 7 hours (at 420 minutes) post-mannitol challenge 1 - FEV1 result recorded at mannitol challenge 2 completion, before initiation of the study intervention (at 430 minutes).

    The efficacy comparison of non-inferiority of PT027 versus PT007 evaluated the while-on-treatment estimand in the PP analysis set and was based on a 1-sided hypothesis testing approach with a non-inferiority margin of -150 mL.

  18. Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis

    Time frame: 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 baseline was defined as the best FEV1 value (the highest FEV1 of the efforts) taken pre-mannitol challenge at - 30 min for Visit 2 and Visit 3.

    The peak fall in FEV1 (in mL) was derived as: FEV1 at 7 hours (at 420 minutes) post-mannitol challenge 1 FEV1 result recorded at mannitol challenge 2 completion, before initiation of the study intervention (at 430 minutes).

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the RS. Superiority was concluded if the 2-sided p-value was < 0.05.

  19. Part 2: Peak Fall in FEV1 From 480 Minutes to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis

    Time frame: 480 minutes post-mannitol challenge 1 and 490 minutes post-mannitol challenge 1

    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 was assessed.

    FEV1 at post-mannitol challenge 2 was the FEV1 result recorded at the end of mannitol challenge 2, i.e. before study intervention treatment, was expected to be at ~490 mins following the mannitol challenge 1.

    If non-inferiority was demonstrated, then comparisons were made to establish the superiority of PT027 versus PT007. The primary efficacy comparison of superiority was based on a 2-sided hypothesis testing approach in the mRS. Superiority was concluded if the 2-sided p-value was < 0.05.

  20. Number of Participants With Adverse Events (AEs)

    Time frame: From Visit 1 until end of follow-up, up to 38 days

    The safety and tolerability of repeated dosing of PT027 as compared to PT007 in participants with asthma on SABA as-needed treatment only were assessed.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Sep 26, 2022
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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