A Study to Assess Drug Absorption of Fixed Dose Combinations of Budesonide, Glycopyrronium, and Formoterol
Condition: Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Treatment A; Treatment B; Treatment C
Intervention description: Participants will receive 2 inhalations of BGF MDI with propellant 1.; Participants will receive 2 inhalations of BGF MDI with propellant 2.; Participants will receive 2 inhalations of BGF MDI with HFA propellant.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Masking description: This is a single blind study with regard to BGF MDI treatment, administered with 3 different propellants (Treatment A, B or C), in which the participants will remain blinded.
Enrollment: 47.0
Sex: Male
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Budesonide; Glycopyrronium; Formoterol; Hydrofluoroalkane; Metered dose inhaler

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]).
    

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:

               1. Systolic blood pressure (BP) < 90 mmHg or > 140 mmHg.

               2. Diastolic BP < 50 mmHg or > 90 mmHg.

               3. Heart rate < 45 or > 85 bpm.

          -  Any CS abnormal findings in vital signs, after 5 minutes supine rest, at screening
             and/or Day -1 of each Treatment Period, as judged by the PI.

          -  Any clinically important abnormalities in rhythm, conduction or morphology of the
             resting electrocardiogram (ECG) and any clinically important abnormalities in the
             12-lead ECG as considered by the PI.

          -  Any positive result on screening for serum hepatitis B surface antigen, hepatitis C
             antibody, and human immunodeficiency virus antibody.

          -  Known or suspected history of drug abuse.

          -  Participant has a positive reverse transcription polymerase chain reaction test for
             severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prior to randomization.

          -  Participant has clinical signs and symptoms consistent with SARS-CoV-2 infection
             (e.g., fever, dry cough, dyspnea, sore throat, fatigue, or laboratory confirmed acute
             infection with SARS-CoV-2).

          -  Participant who had severe course of coronavirus disease 2019 (COVID-19).

          -  Recent (within 14 days prior to admission to the Clinical Unit) exposure to someone
             who has COVID-19 symptoms or tested positive for SARS-CoV-2.

          -  Recent (within 14 days prior to admission to the Clinical Unit) visit to a healthcare
             facility where COVID-19 patients are being treated.

          -  Has a current occupation that involves routine exposure to potential COVID-19 patients
             or sources of SARS-CoV-2 infection.

          -  Has received another new chemical entity (defined as a compound which has not been
             approved for marketing) within 3 months of the first administration of IMP in this
             study.

          -  Plasma donation within 1 month of screening or any blood donation/loss more than 500
             mL during the 3 months prior to screening.

          -  History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or
             history of hypersensitivity to drugs with a similar chemical structure or class to
             BGF.

          -  Current smokers or those who have smoked or used nicotine products (including
             e-cigarettes) within the 3 months prior to screening.

          -  Positive screen for drugs of abuse or cotinine at screening or on admission to the
             Clinical Unit or positive screen for alcohol at screening or on admission to the
             Clinical Unit.

          -  Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks
             prior to the first administration of IMP.

          -  Use of any prescribed or non-prescribed medication including antacids, analgesics,
             herbal remedies, megadose vitamins and minerals during the 2 weeks prior to the first
             administration of IMP or longer if the medication has a long half-life.

          -  Known or suspected history of alcohol abuse or excessive intake of alcohol.

          -  Participants who have previously received BGF.

          -  Judgment by the PI that the participant should not participate in the study if they
             have any ongoing or recent minor medical complaints that may interfere with the
             interpretation of study data or are considered unlikely to comply with study
             procedures, restrictions, and requirements.

          -  Vulnerable participants, eg, kept in detention, protected adults under guardianship,
             trusteeship, or committed to an institution by governmental or juridical order.

          -  History of any respiratory disorders such as asthma, COPD or idiopathic pulmonary
             fibrosis.

          -  Participants who cannot use an inhaler appropriately.

          -  Participants who cannot communicate reliably with the PI.

          -  Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg vector, lipid
             nanoparticle) less than 7 days prior to the date of randomization (from last
             vaccination or booster dose).