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

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

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).

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.