Clinical trial NCT06139991: Study to Assess the Pharmacokinetic Bioequivalence of Budesonide and Albuterol With an Alternate Propellant Compared to Current Propellant.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heathy Participants
Keywords: Albuterol
Budesonide
Combination product
Hydrofluoralkene propellant
Hydrofluoroolefin propellant
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a Partial-replicate, 3-period Cross-over study.
Primary purpose: OTHER

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.

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.
* Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of the study drug.
* Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks or 5 half-lives of the medication, whichever is longer, prior to the first administration of study drug.
* Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
* Excessive intake of caffeine-containing drinks or food.
* Vulnerable participants.

Primary outcomes:
measure: Area under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
Secondary outcomes:
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Time to reach maximum observed concentration (Tmax)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Terminal elimination half-life (T1/2λz)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Apparent total body clearance (CL/F)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Ratio Maximum plasma drug concentration (Cmax)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Ratio Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Ratio Are under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1, Day 2 (pre-dose and post-dose)
measure: Number of participants with Adverse Events
timeFrame: From Screening (≤ 28 days to Day -2) until Follow-up phone call (within 3 to 7 days post final dose)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
Study officials:
References: