A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose

Study Overview
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Brief Summary
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This is a Phase I open-label, single center study to assess the PK and safety of BGF MDI 320/14.4/9.6 µg in subjects with moderate to severe COPD. Pharmacokinetics will be assessed following a single dose administration on the first treatment day (Day 1) and will be assessed again after 7 days of repeat dosing. This study includes a Screening Period of up to 28 days and a single Treatment Period of 8 days. A follow-up phone call will be conducted at least 5 days but no longer than 7 days after the last dose of study drug.

Official Title
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A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: PT010


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Given their signed written informed consent to participate. Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study. Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines. Current or former smokers with a history of at least 10 pack-years of cigarette smoking. Pre-bronchodilator FEV1/FVC ratio must be <0.70 and pre-bronchodilator FEV1 must be ≥50% and <80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations Key Exclusion Criteria: Significant diseases or conditions to : other than COPD, active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease and uncontrolled sleep apnea . Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception. Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma. Subjects who have a history of hypersensitivity to any corticosteroid, β2-agonist, muscarinic anticholinergic, or any component of the MDI Alpha-1 antitrypsin deficiency as the cause of COPD

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT010<br>PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol. | Drug: PT010<br>* PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.<br>* Other names: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) - Budesonide | Maximum plasma concentration (Cmax) - Budesonide | Day 1 | 
| Maximum Plasma Concentration (Cmax) - Budesonide | Maximum plasma concentration (Cmax) - Budesonide | Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose | 
| Maximum Plasma Concentration (Cmax) - Glycopyrronium | Maximum plasma concentration (Cmax) - Glycopyrronium | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose) | 
| Maximum Plasma Concentration (Cmax) - Glycopyrronium | Maximum plasma concentration (Cmax) - Glycopyrronium | Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | 
| Maximum Plasma Concentration (Cmax) - Formoterol | Maximum plasma concentration (Cmax) - Formoterol | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose) | 
| Maximum Plasma Concentration (Cmax) - Formoterol | Maximum plasma concentration (Cmax) - Formoterol | Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide | Day 1 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide | Day 8 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium | Day 1 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium | Day 8 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol | Day 1 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol | Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol | Day 8 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide | Day 1 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium | Day 1 | 
| Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol | Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Plasma Concentration (Tmax) - Budesonide | Time to maximum plasma concentration (tmax) - Budesonide | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | 
| Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium | Time to maximum plasma concentration (tmax) - Glycopyrronium | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | 
| Time to Maximum Plasma Concentration (Tmax) - Formoterol | Time to maximum plasma concentration (tmax) - Formoterol | Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose) | 
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide | Day 1 | 
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium | Day 1 | 
| Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol | Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol | Day 1 |