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

Study identifier:PT010018

ClinicalTrials.gov identifier:NCT03250182

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

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

Medical condition

Chronic Obstructive Pulmonary Disease

Phase

Phase 1

Healthy volunteers

Study drug

PT010

Sex

All

Actual Enrollment

Study type

Interventional

Age

40 Years - 80 Years

Date

Study Start Date: 11 Aug 2017

Primary Completion Date: 07 Dec 2017

Study Completion Date: 07 Dec 2017

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2021 by Pearl Therapeutics, Inc.

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Clearwater, FL, United States, 33765

Arms	Assigned Interventions
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 Name: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at a single center in the United States from August 2017 to December 2017.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Participant Flow: Overall Study

	PT010
STARTED	30
COMPLETED	29
NOT COMPLETED	1
Withdrawal by Subject	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Safety Population: All subjects who received at least 1 dose of study drug.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Baseline Measures

	PT010
Number of Participants [units: Participants]	30
Age Continuous [units: Years] Mean ± Standard Deviation	63.7 ± 7.5
Sex: Female, Male [units: ]
Female	14
Male	16
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	29
More than one race	0
Unknown or Not Reported	0
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	0
Not Hispanic or Latino	30
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Maximum plasma concentration (Cmax) - Budesonide [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Budesonide
Measure Description	Maximum plasma concentration (Cmax) - Budesonide
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Maximum plasma concentration (Cmax) - Budesonide [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	709.3 (57.2%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Budesonide

2. Primary Outcome Measure: 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 ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Budesonide
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Maximum plasma concentration (Cmax) - Budesonide [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	663.2 (65.8%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Budesonide

3. Primary Outcome Measure: 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) ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Glycopyrronium
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Maximum plasma concentration (Cmax) - Glycopyrronium [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	17.2 (80.7%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Glycopyrronium

4. Primary Outcome Measure: 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) ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Glycopyrronium
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	25
Maximum plasma concentration (Cmax) - Glycopyrronium [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	18.3 (65.4%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Glycopyrronium

5. Primary Outcome Measure: 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) ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Formoterol
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Maximum plasma concentration (Cmax) - Formoterol [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	6.4 (48.1%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Formoterol

6. Primary Outcome Measure: 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) ]

Measure Type	Primary
Measure Name	Maximum plasma concentration (Cmax) - Formoterol
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Maximum plasma concentration (Cmax) - Formoterol [units: pg/mL] Geometric Mean (Geometric Coefficient of Variation)	7.4 (38.1%)

No statistical analysis provided for Maximum plasma concentration (Cmax) - Formoterol

7. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Budesonide [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Budesonide
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Area under the plasma concentration-time curve (AUC 0-12) - Budesonide [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	2407.3 (45.4%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Budesonide

8. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Budesonide [ Time Frame: Day 8 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Budesonide
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
Time Frame	Day 8
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Area under the plasma concentration-time curve (AUC 0-12) - Budesonide [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	3004.7 (58.5%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Budesonide

9. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	22
Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	42.5 (45.8%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium

10. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium [ Time Frame: Day 8 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
Time Frame	Day 8
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	23
Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	73.9 (52.9%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Glycopyrronium

11. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Formoterol [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Formoterol
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	25
Area under the plasma concentration-time curve (AUC 0-12) - Formoterol [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	32.6 (30.3%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Formoterol

12. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-12) - Formoterol [ Time Frame: Day 8 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-12) - Formoterol
Measure Description	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
Time Frame	Day 8
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	25
Area under the plasma concentration-time curve (AUC 0-12) - Formoterol [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	47.4 (30.0%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-12) - Formoterol

13. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-tlast) - Budesonide [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-tlast) - Budesonide
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Area under the plasma concentration-time curve (AUC 0-tlast) - Budesonide [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	2731.8 (45.2%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-tlast) - Budesonide

14. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-tlast) - Glycopyrronium [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-tlast) - Glycopyrronium
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Area under the plasma concentration-time curve (AUC 0-tlast) - Glycopyrronium [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	39.4 (73.5%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-tlast) - Glycopyrronium

15. Primary Outcome Measure: Area under the plasma concentration-time curve (AUC 0-tlast) - Formoterol [ Time Frame: Day 1 ]

Measure Type	Primary
Measure Name	Area under the plasma concentration-time curve (AUC 0-tlast) - Formoterol
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Area under the plasma concentration-time curve (AUC 0-tlast) - Formoterol [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	33.4 (43.4%)

No statistical analysis provided for Area under the plasma concentration-time curve (AUC 0-tlast) - Formoterol

16. Secondary Outcome Measure: 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) ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration (tmax) - Budesonide
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Time to maximum plasma concentration (tmax) - Budesonide [units: hours] Median (Full Range)
Day 1	0.33 (0.10 to 1.03)
Day 8	0.67 (0.10 to 2.00)

No statistical analysis provided for Time to maximum plasma concentration (tmax) - Budesonide

17. Secondary Outcome Measure: 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) ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration (tmax) - Glycopyrronium
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	27
Time to maximum plasma concentration (tmax) - Glycopyrronium [units: hours] Median (Full Range)
Day 1	0.03 (0.03 to 4.00)
Day 8	0.10 (0.03 to 1.00)

No statistical analysis provided for Time to maximum plasma concentration (tmax) - Glycopyrronium

18. Secondary Outcome Measure: 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) ]

Measure Type	Secondary
Measure Name	Time to maximum plasma concentration (tmax) - Formoterol
Measure 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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	29
Time to maximum plasma concentration (tmax) - Formoterol [units: hours] Median (Full Range)
Day 1	0.33 (0.10 to 9.97)
Day 8	0.67 (0.03 to 12.00)

No statistical analysis provided for Time to maximum plasma concentration (tmax) - Formoterol

19. Secondary Outcome Measure: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide
Measure Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	24
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	2996.9 (41.0%)

No statistical analysis provided for Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide

20. Secondary Outcome Measure: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium
Measure Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	4
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	61.2 (85.1%)

No statistical analysis provided for Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium

21. Secondary Outcome Measure: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol
Measure Description	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Measured Values

	PT010
Number of Participants Analyzed [units:participants]	7
Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol [units: h*pg/mL] Geometric Mean (Geometric Coefficient of Variation)	46.0 (33.7%)

No statistical analysis provided for Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol

Serious 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.
Additional Description	The Safety Population was defined as all subjects who receive at least 1 dose of study drug.

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg

Serious Adverse Events

	PT010
Total, serious adverse events
# participants affected / at risk	0/30 (0.00%)

Other 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.
Additional Description	The Safety Population was defined as all subjects who receive at least 1 dose of study drug.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
PT010	Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg