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 in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Healthy Participants
- Sponsor
- AstraZeneca
- Enrollment
- 105
- Locations
- 1
- Primary Endpoint
- Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
This study aims to assess the bioequivalence of the total systemic exposure and safety of budesonide, glycopyrronium, and formoterol (160/14.4/4.8 µg/actuation) when administered as BGF MDI HFO compared with BGF MDI HFA in healthy participants.
Detailed Description
This is a Phase I, randomized, double-blind, single-dose, single-site, three way cross-over study to assess the pharmacokinetic (PK) and safety of BGF MDI with HFO propellant compared with BGF MDI with HFA propellant in healthy participants (male or female). The study will comprise of: * A Screening period of up to 27 days; * Three Treatment periods: Participants will receive a single dose of the study intervention on three separate occasions (Period 1, Period 2 and Period 3), with the final dose on Day 2 of Treatment Period 3, and a washout period of 5 to 7 days between administration of each dose; * A final Safety Follow-up within 5 to 7 days after the last administration of the study intervention in Treatment Period 3. Participants will receive all the treatments as a single dose (2 inhalations) (Treatment A \[BGF MDI HFO - test formulation\], and Treatment B \[BGF MDI HFA - reference formulation\]) in one of the 3 possible treatment sequences: ABB, BAB, or BBA. Each participant will be involved in the study for up to 52 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy participants with suitable veins for cannulation or repeated venipuncture.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
- •Females of non-childbearing potential must be confirmed at the Screening Visit.
- •Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 120 kg inclusive.
- •Participants must have a forced expiratory volume in the first second (FEV1) ≥ 80% of the predicted normal value (based on age, height, ethnicity and gender at birth) and an FEV1/forced vital capacity (FEV1/FVC) \> 70% at the Screening Visit. FEV1/FVC can be reported as ratio ie, 0.7 or a percentage ie, 70%.
- •Participants 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 that put the participant at risk of participation.
- •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, history of narrow angle glaucoma not adequately treated, or bladder neck obstruction/urinary retention.
- •Unresectable cancer that has not been in complete remission for at least 5 years.
- •Any clinically significant abnormal findings in physical examination, clinical chemistry, hematology, urinalysis results, or vital signs at Screening.
- •Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at Screening.
- •Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibodies.
- •History of any respiratory disorders such as asthma, COPD, or idiopathic pulmonary fibrosis.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity.
- •Known or suspected history of alcohol or drug abuse as judged by the Investigator.
Outcomes
Primary Outcomes
Area under concentration curve from time 0 to the last quantifiable concentration (AUClast)
Time Frame: Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose
Maximum observed drug concentration (Cmax)
Time Frame: Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose
Secondary Outcomes
- Area under concentration time curve from time 0 to infinity (AUCinf)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Extrapolated area under the curve from time of last quantifiable concentration (tlast) to infinity, expressed as percentage of AUCinf (AUCextr)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Time to reach maximum observed concentration (tmax)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Terminal rate constant (λz)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Terminal elimination half-life (t1/2λz)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Apparent total body clearance (CL/F)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Apparent volume of distribution based on the terminal phase (Vz/F)(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose, and 1, 2, 4, 8, 12 and 24 hours post-dose)