Phase I Study Evaluating the Safety and Pharmacokinetics of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI) in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase I, Randomized, Double-Blind Within Device, Single-Dose, Four-Period, Six-Treatment, Cross-Over Study Evaluating the Safety and Pharmacokinetics of Three Doses of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI), One Dose of Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (GFF MDI), and Two Doses of Symbicort® Inhalation Aerosol in Healthy Volunteers. The primary objective of the study is to determine a dose of budesonide that when formulated with glycopyrronium and formoterol fumarate in BGF MDI provides comparable systemic exposure [pharmacokinetics (PK)] to budesonide following administration of Symbicort MDI.

Official Title
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A Phase I, Randomized, Double-Blind Within Device, Single-Dose, Four-Period, Six-Treatment, Cross-Over Study Evaluating the Safety and Pharmacokinetics of Three Doses of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI), One Dose of Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (GFF MDI), and Two Doses of Symbicort® Inhalation Aerosol in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Inhaled BGF (PT010) Dose 1
* Drug: Inhaled BGF (PT010) Dose 2
* Drug: Inhaled BGF (PT010) Dose 3
* Drug: Inhaled GFF (PT003)
* Drug: Inhaled Symbicort Dose 1
* Drug: Inhaled Symbicort Dose 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed written informed consent form 18 and 45 years (inclusive) Healthy subject confirmed by a thorough medical history and physical examination, ECG, vital signs and clinical laboratory tests Females of childbearing potential and males with female partners of childbearing potential must agree to use medically acceptable contraception Body mass index (BMI) between 18.5 and 32 kg/m2 (inclusive) and a minimum weight of 50 kg at the screening visit Results of complete laboratory analyses should be within the normal range or determined to be not clinically significant by the Investigator Exclusion Criteria: Pregnancy, nursing female subjects, or subjects trying to conceive Clinically significant medical conditions History of ECG abnormalities Symptomatic prostatic hypertrophy, bladder neck obstruction, or urinary retention Known diagnosis of glaucoma Known or suspected history of substance-related disorders within 1 year of screening Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) prior to screening period Hypersensitivity to lactose or any drug or component of the formulation(s) used in this study Positive screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody at screening. Major surgery within four weeks or minor surgery within 2 weeks of drug administration Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGF MDI (PT010) Dose 1<br>BGF MDI Dose 1 taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 2<br> <br> Drug: Inhaled BGF (PT010) Dose 3<br> <br> Drug: Inhaled GFF (PT003)<br> <br> Drug: Inhaled Symbicort Dose 1<br> <br> Drug: Inhaled Symbicort Dose 2<br> <br> |
| Experimental: BGF MDI (PT010) Dose 2<br>BGF MDI Dose 2 taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 1<br> <br> Drug: Inhaled BGF (PT010) Dose 3<br> <br> Drug: Inhaled GFF (PT003)<br> <br> Drug: Inhaled Symbicort Dose 1<br> <br> Drug: Inhaled Symbicort Dose 2<br> <br> |
| Experimental: BGF MDI (PT010) Dose 3<br>BGF MDI Dose 3 taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 1<br> <br> Drug: Inhaled BGF (PT010) Dose 2<br> <br> Drug: Inhaled GFF (PT003)<br> <br> Drug: Inhaled Symbicort Dose 1<br> <br> Drug: Inhaled Symbicort Dose 2<br> <br> |
| Active Comparator: GFF MDI (PT003)<br>GFF MDI (PT003) taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 1<br> <br> Drug: Inhaled BGF (PT010) Dose 2<br> <br> Drug: Inhaled BGF (PT010) Dose 3<br> <br> Drug: Inhaled Symbicort Dose 1<br> <br> Drug: Inhaled Symbicort Dose 2<br> <br> |
| Active Comparator: Symbicort MDI Dose 1<br>Symbicort MDI taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 1<br> <br> Drug: Inhaled BGF (PT010) Dose 2<br> <br> Drug: Inhaled BGF (PT010) Dose 3<br> <br> Drug: Inhaled GFF (PT003)<br> <br> Drug: Inhaled Symbicort Dose 2<br> <br> |
| Active Comparator: Symbicort MDI Dose 2<br>Symbicort MDI Dose 2 taken as 2 inhalations | Drug: Inhaled BGF (PT010) Dose 1<br> <br> Drug: Inhaled BGF (PT010) Dose 2<br> <br> Drug: Inhaled BGF (PT010) Dose 3<br> <br> Drug: Inhaled GFF (PT003)<br> <br> Drug: Inhaled Symbicort Dose 1<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall safety of BGF, GFF, and Symbicort MDI based on the group of outcome measures for safety. | Safety of Three Doses of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI), One Dose of Glycopyrronium and Formoterol Fumarate Inhalation Aerosol (GFF MDI), and Two Doses of Symbicort Inhalation Aerosol. The safety of BGF MDI, Symbicort MDI and GFF MDI will be assessed from physical examination findings, adverse event (AE) reporting including SAE reporting, vital signs (blood pressure, heart rate, respiratory rate and body temperature), clinical laboratory values (hematology, biochemistry, and urinalysis), and findings from 12-lead safety electrocardiograms (ECGs). | 12 hours following study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall pharmacokinetic profile of BGF, GFF, and Symbicort MDI based on the group of outcome measures for pharmacokinetics. | Pharmacokinetics of Budesonide, Glycopyrronium, and Formoterol Fumarate Inhalation Aerosol (BGF MDI), Symbicort MDI and GFF MDI. The PK of BGF MDI, Symbicort MDI and GFF MDI will be assessed and compared from plasma concentrations of each drug. PK parameters at all doses will include Cmax, tmax, t½, AUC0-12, AUC0-t, CL/F, Vd/F, and λz. Other PK parameters may be calculated, as appropriate. | 12 hours following study drug administration |