pt027 compared to pt007 in patients with asthma with mannitol-induced acute airway obstruction

Conditions: Asthma

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

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).

Eligibility criteria:
inclusion criteria: * participants who have been diagnosed with asthma \> 6 months before visit 1 by a physician. * participants must have been prescribed and using as-needed saba as only asthma treatment for at least 4 weeks before screening visit. * participants should have pre-bronchodilator fev1 ≥ 1.5 l and fev1 ≥ 60% to \< 90% predicted normal at visit 1. * participants should have a positive response to mannitol challenge performed at visit 1 (a decrease in fev1 by at least 15% \[pd15\] at ≤ 635 mg). * participants should return to within 10% of baseline fev1 (≥ 90% of baseline fev1), within 1 hour after positive mannitol challenge and 4 inhalations of pt007, performed at visit 1. * participants should be able to adhere to study procedures in the judgment of the investigator. * male or female. * women of childbearing potential must have a negative urine pregnancy test at each study visit. * capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (icf) and in this protocol. * provision of signed and dated written optional genetic research information informed consent prior to collection of samples for optional genetic research that supports genomic initiative. exclusion criteria: * any evidence of clinically significant lung disease other than asthma. * if the participant has had any face-to-face unscheduled or urgent visit for asthma worsening within the last 4 weeks. * any significant disease or disorder, or evidence of drug/substance abuse which in the investigator's opinion would pose a risk to participant safety, interfere with the conduct of study, have an impact on the study results, or make it undesirable for the participant to participate in the study. * if participants have used inhaled corticosteroids (ics) within 1 month prior to enrolment. * if they have used immunosuppressive medication (including but not limited to methotrexate, troleandomycin, cyclosporine, azathioprine, systemic corticosteroids including regular treatment with oral corticosteroids or intramuscular long-acting depot corticosteroids, or any experimental anti-inflammatory therapy) within 3 months prior to enrolment (visit 1) or plan on starting immunosuppressive medications during the study. * if they have used allergen-specific immunotherapy (desensitization) within 3 months prior to enrolment. * if they have used systemic corticosteroids (including oral and injected) within 3 months prior to enrolment. * if they have received any marketed or investigational biologic within 4 months or 5 half-lives prior to enrolment (whichever is longer) or received any investigational nonbiologic agent within 30 days or 5 half-lives prior to enrolment (whichever is longer). * participants with a known hypersensitivity to beta2-agonists, ics, mannitol, or any of the excipients of the product. * any clinically significant abnormal findings in physical examination, vital signs, ecg (eg, participants with qtcf \> 500 ms), hematology, clinical chemistry, or urinalysis, which in the opinion of the investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete entire duration of the study. * if they are current smokers or participants with smoking history ≥ 10 pack years including the use of vaping products, such as electronic cigarettes, and water pipes. if they are former smokers with a smoking history of \<10 pack years, including former vaping or water pipe users, smoking must have stopped for at least 6 months prior to visit 1 to be eligible. * involvement in the planning and/or conduct of the study (applies to both astrazeneca staff and its affiliates and/or staff at the study site and their immediate relative(s)). * judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. * breast feeding, pregnancy or intention to become pregnant during the course of the study. * previous randomization in the present study.

Keywords: acute airway obstruction albuterol budesonide short-acting beta2-agonists (saba) albuterol sulfate