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

• Sponsor: Pearl Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03250182
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arm: 1
• Actual Duration (Months): 3.9
• Patients Per Site Per Month: 7.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: PT010	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration
• Actual Study Start Date: Aug 11, 2017
• Actual Primary Completion Date: Dec 7, 2017
• Actual Study Completion Date: Dec 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PT010 PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol.	Drug: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.; Other Names: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) - Budesonide [Day 1]

   Maximum plasma concentration (Cmax) - Budesonide

2. 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) - Budesonide

3. 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

4. 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) - Glycopyrronium

5. 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

6. Maximum Plasma Concentration (Cmax) - Formoterol [Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)]

   Maximum plasma concentration (Cmax) - Formoterol

7. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide [Day 1]

   Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide

8. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide [Day 8]

   Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide

9. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium [Day 1]

   Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium

10. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium [Day 8]

    Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium

11. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol [Day 1]

    Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol

12. Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol [Day 8]

    Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol

13. Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide [Day 1]

    Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide

14. Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium [Day 1]

    Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium

15. Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol [Day 1]

    Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol

Secondary Outcome Measures

1. 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) - Budesonide

2. 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) - Glycopyrronium

3. 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)]

   Time to maximum plasma concentration (tmax) - Formoterol

4. 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-∞) - Budesonide

5. 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-∞) - Glycopyrronium

6. Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol [Day 1]

   Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Clearwater	Florida	United States	33765

Sponsors and Collaborators

• Pearl Therapeutics, Inc.

Investigators

• Study Director: Paul M Dorinsky, MD, Pearl Therapeutics, Inc.

Study Documents (Full-Text)

• Study Protocol - Jun 14, 2017
• Statistical Analysis Plan - Dec 18, 2017

More Information

Publications

None provided.

• Responsible Party: Pearl Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03250182
• Other Study ID Numbers: PT010018
• First Posted: Aug 15, 2017
• Last Update Posted: Jan 29, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Budesonide; Glycopyrrolate; Formoterol Fumarate

Study Results

Participant Flow

Recruitment Details	This study was conducted at a single center in the United States from August 2017 to December 2017.
Pre-assignment Detail	BGF MDI 320/14.4/9.6 μg oral inhalation as follows: Single-dose on the morning of Day 1 (Visit 3) followed by serial blood draws for 24 hours BID dosing every morning and evening on Day 2 through Day 7 approximately 12 hours apart Single-dose administration on the morning of Day 8 (Visit 5) followed by serial blood draws for 12 hours

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Period Title: Overall Study
STARTED	30
COMPLETED	29
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Overall Participants	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.7 (7.5)
Sex: Female, Male (Count of Participants)
Female	14 46.7%
Male	16 53.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	30 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.3%
White	29 96.7%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Budesonide
Description	Maximum plasma concentration (Cmax) - Budesonide
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	709.3 (57.2)

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Budesonide
Description	Maximum plasma concentration (Cmax) - Budesonide
Time Frame	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	663.2 (65.8)

3. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Glycopyrronium
Description	Maximum plasma concentration (Cmax) - Glycopyrronium
Time Frame	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	17.2 (80.7)

4. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Glycopyrronium
Description	Maximum plasma concentration (Cmax) - Glycopyrronium
Time Frame	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	18.3 (65.4)

5. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Formoterol
Description	Maximum plasma concentration (Cmax) - Formoterol
Time Frame	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	6.4 (48.1)

6. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) - Formoterol
Description	Maximum plasma concentration (Cmax) - Formoterol
Time Frame	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	7.4 (38.1)

7. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	2407.3 (45.4)

8. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	3004.7 (58.5)

9. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	22
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	42.5 (45.8)

10. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	23
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	73.9 (52.9)

11. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	32.6 (30.3)

12. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time Frame	Day 8

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	25
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	47.4 (30.0)

13. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide
Description	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	2731.8 (45.2)

14. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium
Description	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	39.4 (73.5)

15. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol
Description	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	33.4 (43.4)

16. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) - Budesonide
Description	Time to maximum plasma concentration (tmax) - Budesonide
Time Frame	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)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Day 1	0.33
Day 8	0.67

17. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
Description	Time to maximum plasma concentration (tmax) - Glycopyrronium
Time Frame	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)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	27
Day 1	0.03
Day 8	0.10

18. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) - Formoterol
Description	Time to maximum plasma concentration (tmax) - Formoterol
Time Frame	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)

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	29
Day 1	0.33
Day 8	0.67

19. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide
Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	24
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	2996.9 (41.0)

20. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium
Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	4
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	61.2 (85.1)

21. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol
Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.

Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Measure Participants	7
Geometric Mean (Geometric Coefficient of Variation) [h*pg/mL]	46.0 (33.7)

Adverse Events

Time Frame	Adverse events were collected from the time of administration of the first dose of study drug to the time of the final follow-up telephone call up to approximately 7 weeks.
Adverse Event Reporting Description	The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Arm/Group Title	PT010
Arm/Group Description	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
All Cause Mortality
	PT010
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Serious Adverse Events
	PT010
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	PT010
	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)
Blood and lymphatic system disorders
Anaemia	1/30 (3.3%)	1
Gastrointestinal disorders
Dry mouth	1/30 (3.3%)	1
Injury, poisoning and procedural complications
Procedural headache	1/30 (3.3%)	1
Musculoskeletal and connective tissue disorders
Muscular weakness	1/30 (3.3%)	1
Nervous system disorders
Headache	1/30 (3.3%)	1
Restless legs syndrome	1/30 (3.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Drafts of any and all publications or presentations that may arise from this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review and approval and to ensure consistency with the policy in this protocol. Pearl Therapeutics will have the right to request appropriate modification to correct facts and to represent its opinions, or the opinions of the publication committee, if these differ with the proposed publication.