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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
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A (PT027) [experimental], then Treatment B (PT007) [active comparator] Part 1 & 2 | Experimental | 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. |
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| Treatment B (PT007) [active comparator], then Treatment A (PT027) [experimental] Part 1 & 2 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PT027 | Combination Product | When administered PT027, participants will receive 2 actuations of albuterol- budesonide per dose administered as oral inhalations. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | Up to 60 minutes post mannitol challenge 1 |
| Part 1: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | Up to 60 minutes post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Columbia | Maryland | 21046 | United States |
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| Label | URL |
|---|---|
| CSR Synopsis | View source |
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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.
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.
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.
Participants who signed informed consent form (ICF) were enrolled into the study and those who met all eligibility criteria during screening were randomized and treated. All study assessments were performed as per the schedule.
A total of 190 participants who provided the ICF were enrolled and screened at Visit 1. Of these, 105 participants met the eligibility criteria at Visit 2 and were randomized and treated in the study; thus, only data for these participants was collectable and analyzable.
This study was conducted from 28 September 2022 to 18 November 2024 at 11 study centers in the United States of America (USA).
Participants were enrolled separately to Part 1 and Part 2 of the study. Both parts were conducted independently and no cross-over happened between the parts.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment A (PT027) [Experimental], Then Treatment B (PT007) [Active Comparator] Part 1 & 2 | At Visit 2, participants received 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 received repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge. |
| FG001 | Treatment B (PT007) [Active Comparator], Then Treatment A (PT027) [Experimental] Part 1 & 2 | At Visit 2, participants received 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 received repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
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| Part 2 |
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All participants randomly assigned to any of the 2 study treatment sequences and who took at least 1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment A (PT027) [Experimental], Then Treatment B (PT007) [Active Comparator] Part 1 & 2 | At Visit 2, participants received 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 received repeated oral inhalations of PT007 to treat acute airway obstruction induced by a repeated airway challenge. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 60 minutes post mannitol challenge 1 |
From Visit 1 until end of follow-up, up to 38 days
Safety analysis set included all participants randomly assigned to any of the 2 study treatment sequences and who took at least 1 dose of study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment A (PT027) [Experimental] | Participants received repeated oral inhalations (2 actuations) of PT027 to treat acute airway obstruction induced by a repeated airway challenge. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA version 25.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca | 1-877-240-9479 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 10, 2023 | Dec 16, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 3, 2025 | Nov 12, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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The study will enroll 17 participants in Part 1 and 88 participants in Part 2
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| PT007 | Combination Product | When administered PT007, participants will receive 2 actuations of albuterol administered as oral inhalations. |
|
| Up to 60 minutes post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | Up to 60 minutes post mannitol challenge 1 |
| Up to 15 minutes post mannitol challenge 1 |
| Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | Up to 15 minutes post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | Up to 15 minutes post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | Up to 15 minutes post mannitol challenge 1 |
| Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | At 7 hours post mannitol challenge 1 |
| Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Superiority Analysis | 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. | At 7 hours post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | At 480 minutes post mannitol challenge 1 |
| Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Superiority Analysis | 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. | At 480 minutes post mannitol challenge 1 |
| Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Non-Inferiority Analysis | 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. | 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) |
| Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Superiority Analysis | 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. | 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) |
| Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Non-Inferiority Analysis | 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. | 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) |
| Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | 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) |
| Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis | 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. | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
| Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis | 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. | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
| 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 | 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. | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
| Part 2: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
| Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis | 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. | 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1 |
| Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis | 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. | 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1 |
| Part 2: Peak Fall in FEV1 From 480 Minutes to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | 480 minutes post-mannitol challenge 1 and 490 minutes post-mannitol challenge 1 |
| 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 were assessed. | From Visit 1 until end of follow-up, up to 38 days |
| NOT COMPLETED |
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| BG001 | Treatment B (PT007) [Active Comparator], Then Treatment A (PT027) [Experimental] Part 1 & 2 | At Visit 2, participants received 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 received repeated oral inhalations of PT027 to treat acute airway obstruction induced by a repeated airway challenge. |
| BG002 | Total | Total of all reporting groups |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Primary | Part 1: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | RS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pressurized metered dose inhaler (pMDI) Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 60 minutes post mannitol challenge 1 |
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| Primary | Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 60 minutes post mannitol challenge 1 |
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| Primary | Part 2: Change From Mannitol Baseline FEV1 AUC (0-60 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 60 minutes post mannitol challenge 1 |
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| Secondary | Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 15 minutes post mannitol challenge 1 |
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| Secondary | Part 1: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | RS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 15 minutes post mannitol challenge 1 |
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| Secondary | Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 15 minutes post mannitol challenge 1 |
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| Secondary | Part 2: Change From Mannitol Baseline in FEV1 AUC (0-15 Min) Post-mannitol Challenge 1 - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Up to 15 minutes post mannitol challenge 1 |
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| Secondary | Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | At 7 hours post mannitol challenge 1 |
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| Secondary | Part 1: Change From Mannitol Baseline in FEV1 at 7 Hours Post-mannitol Challenge 1 - Superiority Analysis | 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. | RS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | At 7 hours post mannitol challenge 1 |
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| Secondary | Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | At 480 minutes post mannitol challenge 1 |
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| Secondary | Part 2: Change From Mannitol Baseline in FEV1 at 480 Minutes Post-mannitol Challenge 1 - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | At 480 minutes post mannitol challenge 1 |
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| Secondary | Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Median | Inter-Quartile Range | minutes (min) | 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) |
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| Secondary | Part 1: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2 - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Median | Inter-Quartile Range | minutes (min) | 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) |
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| Secondary | Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Non-Inferiority Analysis | 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. | mPP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests) and did not have any important protocol deviations, apart from the deviation of not receiving first dose of investigational medical product (IMP) within 6 minutes of final dose of mannitol challenge 1 (IP03b). Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Median | Inter-Quartile Range | minutes (min) | 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) |
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| Secondary | Part 2: Time to Return to Baseline (-30 Min) FEV1 Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Median | Inter-Quartile Range | minutes (min) | 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) |
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| Secondary | Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
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| Secondary | Part 1: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 μg pMDI Treatment B = PT007 180 μg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
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| Secondary | 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 | 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. | mPP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests) and did not have any important protocol deviations, apart from the deviation of not receiving first dose of investigational medical product (IMP) within 6 minutes of final dose of mannitol challenge 1 (IP03b). Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
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| Secondary | Part 2: Peak Fall in FEV1 From Baseline (-30 Min) FEV1 to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | Baseline (30 minutes prior to mannitol challenge 1) and at 490 minutes post-mannitol challenge 1 |
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| Secondary | Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Non-Inferiority Analysis | 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. | PP analysis set included all participants who received all doses of study treatment following mannitol challenge 1, had baseline and post-treatment study evaluation (spirometry tests), and did not have any important protocol deviations. Challenge 1 referred to the first mannitol challenge for Visits 2 and 3. | Posted | Mean | Standard Deviation | milliliters (mL) | 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1 |
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| Secondary | Part 1: Peak Fall in FEV1 From 7 Hours to Post-mannitol Challenge 2, Pre-dose - Superiority Analysis | 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. | RS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | 420 minutes post-mannitol challenge 1 and 430 minutes post-mannitol challenge 1 |
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| Secondary | Part 2: Peak Fall in FEV1 From 480 Minutes to Post-mannitol Challenge 2, Pre-final Dose of Rescue/Reliever - Superiority Analysis | 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. | mRS included all participants who were randomized to any of the 2 treatment sequences, A/B or B/A and received any amount of randomized study treatment. Treatments A and B were defined as: Treatment A = PT027 180/160 µg pMDI Treatment B = PT007 180 µg pMDI | Posted | Mean | Standard Deviation | milliliters (mL) | 480 minutes post-mannitol challenge 1 and 490 minutes post-mannitol challenge 1 |
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| Secondary | 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 were assessed. | Safety analysis set included all participants randomly assigned to any of the 2 study treatment sequences and who took at least 1 dose of study treatment. | Posted | Count of Participants | Participants | From Visit 1 until end of follow-up, up to 38 days |
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| 0 |
| 100 |
| 0 |
| 100 |
| 5 |
| 100 |
| EG001 | Treatment B (PT007) [Active Comparator] | Participants received repeated oral inhalations (2 actuations) of PT007 to treat acute airway obstruction induced by a repeated airway challenge. | 0 | 101 | 0 | 101 | 4 | 101 |
| Influenza | Infections and infestations | MedDRA version 25.1 | Non-systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA version 25.1 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA version 25.1 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA version 25.1 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA version 25.1 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 25.1 | Non-systematic Assessment |
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| Vertigo positional | Ear and labyrinth disorders | MedDRA version 25.1 | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.1 | Non-systematic Assessment |
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| Influenza like illness | General disorders | MedDRA version 25.1 | Non-systematic Assessment |
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No unpublished information may be disclosed without prior written approval from AstraZeneca
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Any TESAE with outcome death |
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| Any TEAE leading to discontinuation of IMP |
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| Any possibly related TEAE |
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