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

NCT05555290 | Completed Phase 3 Results FDA Drug

• 1 other identifier: D6930C00017
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

A study evaluating efficacy and safety of repeated doses of PT027 compared to PT007 in patients with asthma and acute airway obstruction induced by repeated mannitol challenges

Conditions

Asthma

Keywords

Acute airway obstruction; Albuterol; Budesonide; Short-acting beta2-agonists (SABA); Albuterol Sulfate

Outcome Measures

Primary Outcomes (4)

• 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.

  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

Secondary Outcomes (20)

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

  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

  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

  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

  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

  At 7 hours post mannitol challenge 1

Study Arms (2)

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.

Combination Product: PT027; Combination Product: PT007

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.

Combination Product: PT027; Combination Product: PT007

Interventions

PT027 COMBINATION_PRODUCT

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

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

PT007 COMBINATION_PRODUCT

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

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

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Columbia, Maryland, 21046, United States

Location

Related Links

• CSR Synopsis

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will enroll 17 participants in Part 1 and 88 participants in Part 2

Study Record Dates

• First Submitted: August 25, 2022
• First Posted: September 26, 2022
• Study Start: September 28, 2022
• Primary Completion: November 18, 2024
• Study Completion: November 18, 2024
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)