A Randomized, Single Blind, 3-Period, 3-Treatment, Single-dose, Crossover Study to Assess the Relative Bioavailability of BGF Propellant 1 and BGF Propellant 2 Compared With BGF MDI HFA in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Treatment A
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)
- Sponsor
- AstraZeneca
- Enrollment
- 47
- Locations
- 1
- Primary Endpoint
- Maximum Observed Concentration (Cmax) of BGF MDI
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The study will evaluate bioavailability, pharmacokinetics, safety, and tolerability of budesonide, glycopyrronium and formoterol (BGF) metered dose inhaler (MDI) formulated with 3 different propellants: Propellant 1 (Treatment A [test]), Propellant 2 (Treatment B [test]) and Hydrofluoroalkane (HFA) (Treatment C [reference]).
Detailed Description
The study will comprise: * Screening period: up to 28 days prior to first dosing; * Three treatment periods of maximum 3 days each: participants will be resident from the morning of the day before the first dosing with BGF MDI (Day -1) in Treatment Period 1, throughout all treatment and washout periods up to discharge on Day 2 of Treatment Period 3; * Follow-up: within 3 to 7 days after the last administration of BGF MDI. There will be a washout period of 3 to 7 days between each dose. Each participant will receive 3 single-dose treatments of BGF MDI (1 dose Propellant 1 \[Treatment A\]; 1 dose Propellant 2 \[Treatment B\] and 1 dose HFA \[Treatment C\]), following an overnight fast of at least 8 hours. Each participant will be involved in the study for up to 53 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of signed and dated, written informed consent prior to any study specific procedures.
- •Non-smoking male participants with suitable veins for cannulation or repeated venipuncture.
- •Participants must agree to follow the reproductive restrictions.
- •Have a body mass index between 18 and 30 kg/m\^2 and weigh at least 50 kg and no more than 100 kg.
- •Participants must have a forced expiratory volume in one second ≥ 80% of the predicted value regarding age, height, and ethnicity at the screening visit.
Exclusion Criteria
- •History or current evidence of a clinically significant (CS) disease or disorder (including but not limited to cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary).
- •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 CS illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- •Narrow angle glaucoma not adequately treated. All medications approved for control of intraocular pressures are allowed, including topical ophthalmic non-selective β-blockers.
- •Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the principal investigator (PI), is CS.
- •Any cancer except squamous cell and basal cell carcinomas of the skin are allowed in the study.
- •Any CS abnormalities in clinical chemistry, hematology, or urinalysis results, at screening and/or admission to the Clinical Unit:
- •Systolic blood pressure (BP) \< 90 mmHg or \> 140 mmHg.
- •Diastolic BP \< 50 mmHg or \> 90 mmHg.
- •Heart rate \< 45 or \> 85 bpm.
Arms & Interventions
Treatment Sequence ABC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment B; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence ABC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment B; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence ABC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment B; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Treatment Sequence BCA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment C; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence BCA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment C; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence BCA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment C; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Treatment Sequence CAB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment A; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence CAB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment A; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence CAB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment A; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Treatment Sequence ACB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment C; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence ACB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment C; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence ACB
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment A; Treatment C; Treatment B) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Treatment Sequence BAC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment A; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence BAC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment A; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence BAC
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment B; Treatment A; Treatment C) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Treatment Sequence CBA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment B; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment A
Treatment Sequence CBA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment B; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment B
Treatment Sequence CBA
Participants will be randomized to one of the 6 different treatment sequences. Each participant will receive 3 single-dose treatments of BGF MDI (Treatment C; Treatment B; Treatment A) in 3 treatment periods, with first dose on Day -1 for all treatment periods.
Intervention: Treatment C
Outcomes
Primary Outcomes
Maximum Observed Concentration (Cmax) of BGF MDI
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
Evaluation of the relative bioavailability between the test formulations and the reference formulation for fixed dose combinations (FDCs) of BGF when delivered as BGF MDI with 3 different propellants by Cmax.
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BGF MDI
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
Evaluation of the relative bioavailability between the test formulations and the reference formulation for FDCs of BGF when delivered as BGF MDI with 3 different propellants by AUCinf.
Area Under the Plasma Concentration- Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of BGF MDI
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
Evaluation of the relative bioavailability between the test formulations and the reference formulation for FDCs of BGF when delivered as BGF MDI with 3 different propellants by AUClast.
Secondary Outcomes
- Terminal Elimination Half-life (t½λz) of BGF MDI(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose)
- Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events(Screening, Day -1 until Follow-up visit, up to 53 days)
- Apparent Total Body Clearance of Drug After Extravascular Administration (CL/F) of BGF MDI(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) of BGF MDI(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 During the Terminal Phase After Extravascular Administration (Vz/F) of BGF MDI(Pre-dose and 2, 5, 10, 20, 30, and 45 minutes post-dose and 1, 2, 4, 8, 12 and 24 hours post-dose)