A Phase I, Randomized, Double-blind, Single-dose, Partial-replicate, 3-way Cross-over Study to Assess the Total Systemic Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- AstraZeneca
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
The study will evaluate bioequivalence, pharmacokinetics, safety, and tolerability of Budesonide, Glycopyrronium and Formoterol (BGF) metered dose inhaler (MDI) formulated with hydrofluoroolefin (HFO) [Test] and hydrofluoroalkane (HFA) [Reference] in healthy participants (male or female).
Detailed Description
This is a Phase I, randomized, double-blind, single-dose, single-center, partial-replicate, 3 way cross-over study to assess pharmacokinetic and safety of BGF MDI when administered with different propellants, HFO (HFO-1234ze) - test and HFA (HFA-134a) - reference. The study will comprise of: * A screening period up to 28 days prior to first dosing; * Three Treatment Periods: Participants will be resident at the Clinical Unit from the morning on the day before dosing with BGF MDI on Day -1 of Treatment Period 1, until 24 hours following the final dose on Day 2 of Treatment Period 3, with a washout period of 3 to 7 days between each dose; and * Follow-up: final safety Follow-up Phone Call within 3 to 7 days after the last administration of BGF MDI in Treatment Period 3. Each participant will receive 3 single dose treatments of BGF MDI (Treatment A: BGF MDI HFO \[Test\]; Treatment B: BGF MDI HFA \[Reference\]) following an overnight fast of at least 8 hours on Day 1 of each treatment period. The reference formulation will be administered during 2 of the 3 treatment periods. There will be a minimum of a 3 to 7 day washout between administration of each treatment. Each participant will be involved in the study for approximately 55 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Healthy male and female subjects aged 18 to 60 years with suitable veins for cannulation or repeated venepuncture.
- •Females must have a negative pregnancy test, must not be lactating
- •Have a Body Mass Index (BMI) between 18 and 35 kg/m2 inclusive and weigh at least 50 kg and no more than 120 kg inclusive.
- •Subjects must have a FEV1 ≥ 80% of the predicted normal value and an FEV1/FVC \> 70% regarding age, height, and ethnicity.
- •Subjects must demonstrate proper inhalation technique and have the ability to properly use an MDI device after training.
Exclusion Criteria
- •History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate.
- •History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- •History of narrow angle glaucoma not adequately treated and/or change in vision that may be relevant.
- •History of symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the investigator, is clinically significant.
- •Unresectable cancer that has not been in complete remission for at least 5 years.
- •Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results at screening, as judged by the investigator.
- •Any clinically significant abnormalities on 12-lead electrocardiogram (ECG)
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- •Subject has a positive Reverse transcriptase- Polymerase chain reaction (RT-PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Outcomes
Primary Outcomes
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
Time Frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
The AUCinf of budesonide, glycopryrronium and formoterol in participants was evaluated.
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
Time Frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
The AUClast of budesonide, glycopryrronium and formoterol in participants was evaluated.
Maximum Observed Plasma (Peak) Drug Concentration (Cmax)
Time Frame: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
The Cmax of budesonide, glycopryrronium and formoterol in participants was evaluated.
Secondary Outcomes
- Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Mean Residence Time of the Unchanged Drug in the Systemic Circulation From Zero to Infinity (MRTinf)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Apparent Total Body Clearance of Drug From Plasma After Extravascular Administration (CL/F)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Volume of Distribution (Apparent) at Steady State Following Extravascular Administration (Based on Terminal Phase) (Vz/F)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From Screening up to Follow-up (3 to 7 days post final dose) [approximately 55 days])