Study to Assess the Pharmacokinetic Bioequivalence of Budesonide and Albuterol With an Alternate Propellant Compared to Current Propellant.

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Heathy Participants
• Intervention / Treatment: Drug: Treatment B (BDA MDI HFA); Drug: Treatment A (BDA MDI HFO)

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.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Treatment B (BDA MDI HFA); Randomized participants will receive Treatment B (BDA MDI HFA) on Day 1 under fasted condition.; Drug: Treatment A (BDA MDI HFO); Randomized participants will receive Treatment A (BDA MDI HFO) on Day 1 under fasted condition.
Experimental: 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.	Drug: Treatment B (BDA MDI HFA); Randomized participants will receive Treatment B (BDA MDI HFA) on Day 1 under fasted condition.; Drug: Treatment A (BDA MDI HFO); Randomized participants will receive Treatment A (BDA MDI HFO) on Day 1 under fasted condition.
Experimental: 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.	Drug: Treatment B (BDA MDI HFA); Randomized participants will receive Treatment B (BDA MDI HFA) on Day 1 under fasted condition.; Drug: Treatment A (BDA MDI HFO); Randomized participants will receive Treatment A (BDA MDI HFO) on Day 1 under fasted condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)	The AUClast of budesonide and albuterol will be evaluated to assess the bioequivalence of the total systemic exposure of budesonide and albuterol administered.	Day 1, Day 2 (pre-dose and post-dose)
Maximum plasma drug concentration (Cmax)	The Cmax of budesonide and albuterol will be evaluated to assess the bioequivalence of the total systemic exposure of budesonide and albuterol administered.	Day 1, Day 2 (pre-dose and post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve from time 0 to infinity (AUCinf)	The AUCinf after administration of budesonide and albuterol will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Time to reach maximum observed concentration (Tmax)	The Tmax after administration of budesonide and albuterol will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Terminal elimination half-life (T1/2λz)	The T1/2λz after administration of budesonide and albuterol will be evaluated.	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)	The MRT after administration of budesonide and albuterol will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Apparent total body clearance (CL/F)	The CL/F after administration of budesonide and albuterol will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Apparent volume of distribution during the terminal phase (Vz/F)	The Vz/F after administration of budesonide and albuterol will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Ratio Maximum plasma drug concentration (Cmax)	The ratio of Treatment A (test formulation) and Treatment B (reference formulation) Cmax values will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Ratio Area under plasma concentration-time curve from time 0 to infinity (AUCinf)	The ratio of Treatment A (test formulation) and Treatment B (reference formulation) AUCinf values will be evaluated.	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)	The ratio of Treatment A (test formulation) and Treatment B (reference formulation) AUClast values will be evaluated.	Day 1, Day 2 (pre-dose and post-dose)
Number of participants with Adverse Events	The safety and tolerability of single doses of BDA MDI HFO and BDA MDI HFA will be evaluated.	From Screening (≤ 28 days to Day -2) until Follow-up phone call (within 3 to 7 days post final dose)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): May 13, 2024
• Study Completion (Estimated): May 13, 2024

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Budesonide; Albuterol; Combination product; Hydrofluoralkene propellant; Hydrofluoroolefin propellant
• Other Study ID Numbers: D6933C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No