Trial Outcomes & Findings for A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose (NCT NCT03250182)

NCT ID: NCT03250182

Last Updated: 2021-01-29

Results Overview

Maximum plasma concentration (Cmax) - Budesonide

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome timeframe: Day 1
• Results posted on: 2021-01-29

Participant Flow

This study was conducted at a single center in the United States from August 2017 to December 2017.

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

Participant milestones

Measure	PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Overall Study STARTED	30
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	PT010 Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	PT010 n=30 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Age, Continuous	63.7 Years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1

Population: 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.

Maximum plasma concentration (Cmax) - Budesonide

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Budesonide	709.3 pg/mL Geometric Coefficient of Variation 57.2

PRIMARY outcome

Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose

Population: 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.

Maximum plasma concentration (Cmax) - Budesonide

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Budesonide	663.2 pg/mL Geometric Coefficient of Variation 65.8

PRIMARY outcome

Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)

Population: 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.

Maximum plasma concentration (Cmax) - Glycopyrronium

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Glycopyrronium	17.2 pg/mL Geometric Coefficient of Variation 80.7

PRIMARY outcome

Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)

Population: 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.

Maximum plasma concentration (Cmax) - Glycopyrronium

Outcome measures

Measure	PT010 n=25 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Glycopyrronium	18.3 pg/mL Geometric Coefficient of Variation 65.4

PRIMARY outcome

Timeframe: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)

Population: 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.

Maximum plasma concentration (Cmax) - Formoterol

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Formoterol	6.4 pg/mL Geometric Coefficient of Variation 48.1

PRIMARY outcome

Timeframe: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)

Population: 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.

Maximum plasma concentration (Cmax) - Formoterol

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Maximum Plasma Concentration (Cmax) - Formoterol	7.4 pg/mL Geometric Coefficient of Variation 38.1

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide	2407.3 h*pg/mL Geometric Coefficient of Variation 45.4

PRIMARY outcome

Timeframe: Day 8

Population: 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.

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

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide	3004.7 h*pg/mL Geometric Coefficient of Variation 58.5

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=22 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium	42.5 h*pg/mL Geometric Coefficient of Variation 45.8

PRIMARY outcome

Timeframe: Day 8

Population: 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.

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

Outcome measures

Measure	PT010 n=23 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium	73.9 h*pg/mL Geometric Coefficient of Variation 52.9

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=25 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol	32.6 h*pg/mL Geometric Coefficient of Variation 30.3

PRIMARY outcome

Timeframe: Day 8

Population: 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.

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

Outcome measures

Measure	PT010 n=25 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol	47.4 h*pg/mL Geometric Coefficient of Variation 30.0

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide	2731.8 h*pg/mL Geometric Coefficient of Variation 45.2

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium	39.4 h*pg/mL Geometric Coefficient of Variation 73.5

PRIMARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol	33.4 h*pg/mL Geometric Coefficient of Variation 43.4

SECONDARY outcome

Timeframe: 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)

Population: 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.

Time to maximum plasma concentration (tmax) - Budesonide

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Time to Maximum Plasma Concentration (Tmax) - Budesonide Day 1	0.33 hours Interval 0.1 to 1.03
Time to Maximum Plasma Concentration (Tmax) - Budesonide Day 8	0.67 hours Interval 0.1 to 2.0

SECONDARY outcome

Timeframe: 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)

Population: 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.

Time to maximum plasma concentration (tmax) - Glycopyrronium

Outcome measures

Measure	PT010 n=27 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium Day 1	0.03 hours Interval 0.03 to 4.0
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium Day 8	0.10 hours Interval 0.03 to 1.0

SECONDARY outcome

Timeframe: 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)

Population: 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.

Time to maximum plasma concentration (tmax) - Formoterol

Outcome measures

Measure	PT010 n=29 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Time to Maximum Plasma Concentration (Tmax) - Formoterol Day 1	0.33 hours Interval 0.1 to 9.97
Time to Maximum Plasma Concentration (Tmax) - Formoterol Day 8	0.67 hours Interval 0.03 to 12.0

SECONDARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=24 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide	2996.9 h*pg/mL Geometric Coefficient of Variation 41.0

SECONDARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=4 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium	61.2 h*pg/mL Geometric Coefficient of Variation 85.1

SECONDARY outcome

Timeframe: Day 1

Population: 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.

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

Outcome measures

Measure	PT010 n=7 Participants Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol	46.0 h*pg/mL Geometric Coefficient of Variation 33.7

Adverse Events

PT010

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	PT010 n=30 participants at risk Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
Nervous system disorders Headache	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Nervous system disorders Restless legs syndrome	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Blood and lymphatic system disorders Anaemia	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Gastrointestinal disorders Dry mouth	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Injury, poisoning and procedural complications Procedural headache	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	3.3% 1/30 • Number of events 1 • 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. The Safety Population was defined as all subjects who receive at least 1 dose of study drug.

Additional Information

Pearl Therapeutics, Inc.

Pearl Therapeutics, Inc.

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER