A Phase 1, Randomized, Double-blind, Single-dose, Partial Replicate, 3-period Cross-over Study to Assess the Total Systemic Exposure Bioequivalence of Budesonide and Albuterol Delivered by BDA MDI Hydrofluoroolefin (HFO) Compared With BDA MDI (Hydrofluoroalkene) HFA.
Overview
- Phase
- Phase 1
- Intervention
- Treatment A (BDA MDI HFO)
- Conditions
- Heathy Participants
- Sponsor
- AstraZeneca
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Area under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study will investigate the Pharmacokinetic (PK) and safety of Budesonide and albuterol (BDA) metered dose inhaler (MDI) HFO and BDA MDI HFA in healthy male and female participants.
Detailed Description
Eligible participant will receive 3 single-dose treatments; 2 doses of BDA MDI HFA and 1 dose of BDA MDI HFO. * Treatment A: 2 inhalations, single dose of BDA MDI HFO 80/90 μg (test formulation) * Treatment B: 2 inhalations, single dose of BDA MDI HFA 80/90 μg (reference formulation) Participants will be randomly assigned to receive any 1 of the 3 treatment sequences of ABB, BBA or BAB. The study will comprise of: * A screening period of maximum 28 days. * Three Treatment periods will be up to approximately 22 days (including Follow-up). * A final follow-up calls within 3-7 days after the last dose of study intervention. Each participant has to be involved in the study for up to 48 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male and female participants (of non-childbearing potential) aged 18 to 60 years, inclusive, with suitable veins for cannulation or repeated venipuncture.
- •Female participants must have a negative pregnancy test at screening and on admission and must not be lactating.
- •Participants with Body mass index between 18 and 30 kg/m\^2, inclusive, and weighing between 50 kg and no more than 120 kg inclusive.
- •Participants must have a Forced expiratory volume (FEV)1 ≥ 80% of the predicted normal value and an FEV1/FVC\> 70% regarding age, height, and ethnicity at the screening visit.
- •Participants must demonstrate proper inhalation technique and is able to use an MDI properly after training.
Exclusion Criteria
- •History or presence of gastrointestinal, hepatic or renal disease, or any other clinically significant disease or disorder.
- •History of any clinically significant disease or disorder which may either put the participant at risk because of participation in the study or influence the results or the participant's ability to participate in the study.
- •Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug.
- •Any clinically important abnormalities in clinical chemistry, haematology, or urinalysis results at the screening.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, or Human immunodeficiency virus (HIV).
- •Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
- •Known or suspected history of alcohol or drug abuse.
- •Positive screen for drugs of abuse, alcohol, or cotinine at screening.
- •History or presence of severe allergy/hypersensitivity.
Arms & Interventions
Treatment sequence ABB
Participants will receive Treatment A, followed by Treatment B, followed by Treatment B, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment A (BDA MDI HFO)
Treatment sequence ABB
Participants will receive Treatment A, followed by Treatment B, followed by Treatment B, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment B (BDA MDI HFA)
Treatment sequence BBA
Participants will receive Treatment B, followed by Treatment B, followed by Treatment A, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment A (BDA MDI HFO)
Treatment sequence BBA
Participants will receive Treatment B, followed by Treatment B, followed by Treatment A, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment B (BDA MDI HFA)
Treatment sequence BAB
Participants will receive Treatment B, followed by Treatment A, followed by Treatment B, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment A (BDA MDI HFO)
Treatment sequence BAB
Participants will receive Treatment B, followed by Treatment A, followed by Treatment B, all treatments as a single dose, with a washout period of minimum 3 days, but no longer than 7 days, between each study dose administration.
Intervention: Treatment B (BDA MDI HFA)
Outcomes
Primary Outcomes
Area under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
Time Frame: Day 1, Day 2 (pre-dose and post-dose)
The AUClast of budesonide and albuterol will be evaluated to assess the bioequivalence of the total systemic exposure of budesonide and albuterol administered.
Maximum plasma drug concentration (Cmax)
Time Frame: Day 1, Day 2 (pre-dose and post-dose)
The Cmax of budesonide and albuterol will be evaluated to assess the bioequivalence of the total systemic exposure of budesonide and albuterol administered.
Secondary Outcomes
- Terminal elimination half-life (T1/2λz)(Day 1, Day 2 (pre-dose and post-dose))
- Ratio Area under plasma concentration-time curve from time 0 to infinity (AUCinf)(Day 1, Day 2 (pre-dose and post-dose))
- Time to reach maximum observed concentration (Tmax)(Day 1, Day 2 (pre-dose and post-dose))
- Area under plasma concentration-time curve from time 0 to infinity (AUCinf)(Day 1, Day 2 (pre-dose and post-dose))
- Ratio Are under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(Day 1, Day 2 (pre-dose and post-dose))
- Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)(Day 1, Day 2 (pre-dose and post-dose))
- Apparent volume of distribution during the terminal phase (Vz/F)(Day 1, Day 2 (pre-dose and post-dose))
- Apparent total body clearance (CL/F)(Day 1, Day 2 (pre-dose and post-dose))
- Ratio Maximum plasma drug concentration (Cmax)(Day 1, Day 2 (pre-dose and post-dose))
- Number of participants with Adverse Events(From Screening (≤ 28 days to Day -2) until Follow-up phone call (within 3 to 7 days post final dose))