Trial Outcomes & Findings for Crossover Study to Assess the Efficacy of PT003 With and Without a Valved Holding Chamber in Subjects With Moderate to Severe COPD (NCT NCT02454959)

NCT ID: NCT02454959

Last Updated: 2017-04-19

Results Overview

AUC0-12 was calculated using the trapezoidal rule based on FEV1 assessments at pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours post-dosing of study drug. Primary Outcome was calculated using the trapezoidal rule and was modeled conditionally on baseline FEV1.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 80 participants
• Primary outcome timeframe: 7 days of treatment
• Results posted on: 2017-04-19

Participant Flow

This is a randomized, 2-period, open-label, chronic dosing (7 days), cross-over study conducted at 8 sites in the US.

Subject received one week of study treatment for each of the treatment periods, separated by a washout period of 7-14 days between treatments. Intent-to-treat (ITT) Population is used for Participant Flow. By-sequence tabulations of the data were not pre-specified.

Participant milestones

Measure	Overall Study All Randomized Patients
Overall Study STARTED	79
Overall Study GFF MDI (PT003) With Aerochamber	73
Overall Study GFF MDI (PT003) Without Aerochamber	77
Overall Study COMPLETED	70
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	Overall Study All Randomized Patients
Overall Study Protocol-Specified Criteria	3
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	2

Baseline Characteristics

Crossover Study to Assess the Efficacy of PT003 With and Without a Valved Holding Chamber in Subjects With Moderate to Severe COPD

Baseline characteristics by cohort

Measure	MITT Population n=68 Participants The Modified ITT (MITT) Population is a subset of the ITT Population including subjects who received treatment and had post dose efficacy data from both Treatment Periods. Data judged to be impacted by major protocol deviations were determined prior to unblinding and excluded. Statistical tabulations and analyses are by randomized treatment, but data obtained after subjects received an incorrect treatment have been excluded from the affected periods.
Age, Continuous	62.5 Years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: 7 days of treatment

Population: The primary analysis used the Modified-Intent-to-Treat (MITT) Population.

AUC0-12 was calculated using the trapezoidal rule based on FEV1 assessments at pre-dose, and 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours post-dosing of study drug. Primary Outcome was calculated using the trapezoidal rule and was modeled conditionally on baseline FEV1.

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=67 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=68 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Area Under the Curve for Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) From 0 to 12 Hours (AUC0-12) on Day 8	1.538 Liter Standard Error 0.0228	1.516 Liter Standard Error 0.0227

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter AUC0-12 of Glycopyrronium by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=56 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=56 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
AUC0-12 on Day 8	128.00 h*pg/mL Standard Deviation 85.63	111.39 h*pg/mL Standard Deviation 63.54

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter AUC0-12 of Formoterol by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=49 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=51 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
AUC0-12 on Day 8	75.46 h*pg/mL Standard Deviation 43.29	78.49 h*pg/mL Standard Deviation 39.17

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter Cmax of Glycopyrronium by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=62 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=67 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Cmax on Day 8	34.03 pg/mL Standard Deviation 21.87	26.55 pg/mL Standard Deviation 15.11

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter Cmax of Formoterol by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=62 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=67 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Cmax on Day 8	12.53 pg/mL Standard Deviation 5.88	13.07 pg/mL Standard Deviation 7.50

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter tmax of Glycopyrronium by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=62 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=67 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Tmax on Day 8	0.10 h Full Range 21.87 • Interval 0.03 to 10.02	0.12 h Full Range 15.11 • Interval 0.03 to 8.0

SECONDARY outcome

Timeframe: Day 8

Population: Pharmacokinetic Population

Pharmacokinetic Parameter tmax of Formoterol by Treatment on Day 8

Outcome measures

Measure	GFF MDI (PT003) With Aerochamber n=62 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=67 Participants Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Tmax on Day 8	0.33 h Full Range 21.87 • Interval 0.0 to 10.02	0.37 h Full Range 15.11 • Interval 0.37 to 10.17

Adverse Events

GFF MDI (PT003) With Aerochamber

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

GFF MDI (PT003) Without Aerochamber

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	GFF MDI (PT003) With Aerochamber n=74 participants at risk Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=78 participants at risk Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Gastrointestinal disorders Pancreatitis	1.4% 1/74 • Number of events 1 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.00% 0/78 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/74 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.3% 1/78 • Number of events 1 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Vascular disorders Deep Vein Thrombosis	0.00% 0/74 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.3% 1/78 • Number of events 1 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.

Other adverse events

Measure	GFF MDI (PT003) With Aerochamber n=74 participants at risk Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID with Aerochamber Plus Valved Holding Chamber	GFF MDI (PT003) Without Aerochamber n=78 participants at risk Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003 (GFF MDI) 14.4/9.6 µg BID without Aerochamber Plus Valved Holding Chamber
Investigations Blood potassium increased	0.00% 0/74 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.6% 2/78 • Number of events 2 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/74 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.6% 2/78 • Number of events 2 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/74 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.6% 2/78 • Number of events 2 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
General disorders Vessel puncture site swelling	1.4% 1/74 • Number of events 2 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.6% 2/78 • Number of events 4 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Vascular disorders Hypertension	2.7% 2/74 • Number of events 2 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.00% 0/78 • Adverse events collected from the time the subject signed consent up to the follow-up phone call 7-14 days after last dose of study drug. Any Adverse Events reported as starting during a Washout Period were assigned to the last randomized treatment received including those occurring during a Washout Period or the Follow-up Period. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.

Additional Information

Colin Reisner, MD, FCCP, FAAAAI

Pearl Therapeutics, Inc.

Phone: 650-305-2600

Email: creisner@pearltherapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER