Trial Outcomes & Findings for Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects With Moderate to Very Severe COPD (NCT NCT02343458)

Last Updated: 2019-02-20

Results Overview

For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1756 participants

Primary outcome timeframe

at week 24

Results posted on

2019-02-20

Participant Flow

The study was conducted at 175 sites in the United States, United Kingdom, Taiwan (TW),South Korea (SK), Russia, Poland, Hungary, Germany, Czech Republic, China, and Japan from April 2015 to August 2017. The entire study period was scheduled to take approximately 30 weeks for each individual subject from the time of screening.

Subjects were randomized in a 7:6:6:3 scheme (GFF MDI, FF MDI, GP MDI, and Placebo MDI). Randomization was stratified by reversibility to Ventolin HFA and COPD disease severity (moderate vs severe or very severe) to ensure a similar distribution of treatment arms across stratum.

Participant milestones

Participant milestones
Measure	GFF MDI 14.4/9.6 ug Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI Placebo Metered Dose Inhalation
Overall Study STARTED	555	483	480	238
Overall Study COMPLETED	494	417	417	200
Overall Study NOT COMPLETED	61	66	63	38

Reasons for withdrawal

Reasons for withdrawal
Measure	GFF MDI 14.4/9.6 ug Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI Placebo Metered Dose Inhalation
Overall Study Adverse Event	15	14	15	3
Overall Study Lack of Efficacy	3	8	4	8
Overall Study Withdrawal by Subject	18	17	23	14
Overall Study Physician Decision	1	4	2	2
Overall Study Lost to Follow-up	5	5	3	1
Overall Study Protocol Violation	2	5	2	2
Overall Study Protocol Specified Criteria	17	13	14	8

Baseline Characteristics

ITT Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GFF MDI 14.4/9.6 ug n=551 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=480 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=474 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=235 Participants Placebo Metered Dose Inhalation	Total n=1740 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 7.4 • n=5 Participants • ITT Population	64.1 Years STANDARD_DEVIATION 7.6 • n=7 Participants • ITT Population	64.0 Years STANDARD_DEVIATION 8.1 • n=5 Participants • ITT Population	63.9 Years STANDARD_DEVIATION 7.5 • n=4 Participants • ITT Population	64.2 Years STANDARD_DEVIATION 7.7 • n=21 Participants • ITT Population
Sex: Female, Male Female	143 Participants n=5 Participants • The data reported from one site was not included in the final analysis	115 Participants n=7 Participants • The data reported from one site was not included in the final analysis	128 Participants n=5 Participants • The data reported from one site was not included in the final analysis	64 Participants n=4 Participants • The data reported from one site was not included in the final analysis	450 Participants n=21 Participants • The data reported from one site was not included in the final analysis
Sex: Female, Male Male	408 Participants n=5 Participants • The data reported from one site was not included in the final analysis	365 Participants n=7 Participants • The data reported from one site was not included in the final analysis	346 Participants n=5 Participants • The data reported from one site was not included in the final analysis	171 Participants n=4 Participants • The data reported from one site was not included in the final analysis	1290 Participants n=21 Participants • The data reported from one site was not included in the final analysis
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants • ITT Population	0 Participants n=7 Participants • ITT Population	0 Participants n=5 Participants • ITT Population	0 Participants n=4 Participants • ITT Population	1 Participants n=21 Participants • ITT Population
Race (NIH/OMB) Asian	223 Participants n=5 Participants • ITT Population	204 Participants n=7 Participants • ITT Population	181 Participants n=5 Participants • ITT Population	92 Participants n=4 Participants • ITT Population	700 Participants n=21 Participants • ITT Population
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • ITT Population	0 Participants n=7 Participants • ITT Population	0 Participants n=5 Participants • ITT Population	0 Participants n=4 Participants • ITT Population	0 Participants n=21 Participants • ITT Population
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants • ITT Population	16 Participants n=7 Participants • ITT Population	18 Participants n=5 Participants • ITT Population	6 Participants n=4 Participants • ITT Population	52 Participants n=21 Participants • ITT Population
Race (NIH/OMB) White	315 Participants n=5 Participants • ITT Population	260 Participants n=7 Participants • ITT Population	275 Participants n=5 Participants • ITT Population	137 Participants n=4 Participants • ITT Population	987 Participants n=21 Participants • ITT Population
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • ITT Population	0 Participants n=7 Participants • ITT Population	0 Participants n=5 Participants • ITT Population	0 Participants n=4 Participants • ITT Population	0 Participants n=21 Participants • ITT Population
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • ITT Population	0 Participants n=7 Participants • ITT Population	0 Participants n=5 Participants • ITT Population	0 Participants n=4 Participants • ITT Population	0 Participants n=21 Participants • ITT Population

PRIMARY outcome

Timeframe: at week 24

Population: ITT Population - defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects were analyzed according to the treatment they were assigned to at randomization. Number of participants analyzed reflects the ITT population with available data

For the US/China approach, the primary endpoint was the change from baseline in morning pre-dose trough FEV1 at Week 24 of treatment

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=488 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=413 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=412 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=196 Participants Placebo Metered Dose Inhalation
Change From Baseline in Morning Pre-dose Trough FEV1 at Week 24 of Treatment (US/China Approach)	120 mL Interval 102.0 to 138.0	47 mL Interval 28.0 to 67.0	60 mL Interval 41.0 to 80.0	-45 mL Interval -73.0 to -17.0

PRIMARY outcome

Timeframe: over weeks 12-24

Change from baseline in morning pre-dose trough FEV1 over weeks 12-24, Japan approach

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=517 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=436 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=437 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=205 Participants Placebo Metered Dose Inhalation
Change From Baseline in Morning Pre-dose Trough FEV1 Over Weeks 12-24, Japan Approach	128 mL Interval 113.0 to 143.0	54 mL Interval 38.0 to 71.0	74 mL Interval 58.0 to 91.0	-25 mL Interval -49.0 to -1.0

PRIMARY outcome

Timeframe: over 24 weeks

Change from baseline in morning pre-dose trough FEV1 over 24 weeks. Primary endpoint, EU/SK/TW approach, Secondary endpoint US/China approach.

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=541 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=467 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=465 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=225 Participants Placebo Metered Dose Inhalation
Change From Baseline in Morning Pre-dose Trough FEV1 Over 24 Weeks. Primary Endpoint, EU/SK/TW Approach, Secondary Endpoint US/China Approach.	135 mL Interval 121.0 to 149.0	63 mL Interval 48.0 to 78.0	80 mL Interval 65.0 to 94.0	-20 mL Interval -41.0 to 2.0

SECONDARY outcome

Timeframe: over 24 Weeks

TDI focal score over 24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=532 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=458 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=457 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=217 Participants Placebo Metered Dose Inhalation
TDI Focal Score Over 24 Weeks, US/China and EU/SK/TW Approach	1.6 Scores on a scale Interval 1.4 to 1.8	1.5 Scores on a scale Interval 1.3 to 1.7	1.3 Scores on a scale Interval 1.1 to 1.5	0.8 Scores on a scale Interval 0.5 to 1.1

SECONDARY outcome

Timeframe: over Weeks 12-24

TDI focal score over 12-24 Weeks as a Model-Based Average (ITT Population) The TDI is an instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=515 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=434 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=436 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=205 Participants Placebo Metered Dose Inhalation
TDI Focal Score Over Weeks 12-24 Japan Approach	1.7 Scores on a scale Interval 1.5 to 1.9	1.5 Scores on a scale Interval 1.3 to 1.7	1.4 Scores on a scale Interval 1.2 to 1.6	0.8 Scores on a scale Interval 0.5 to 1.1

SECONDARY outcome

Timeframe: over 24 Weeks

Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=244 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=217 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=228 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=108 Participants Placebo Metered Dose Inhalation
TDI Focal Score Over 24 Weeks - US/China and EU/SK/TW Approaches -Symptomatic Population	1.5 Scores on a scale Interval 1.2 to 1.7	1.3 Scores on a scale Interval 1.0 to 1.6	1.1 Scores on a scale Interval 0.8 to 1.3	0.7 Scores on a scale Interval 0.3 to 1.2

SECONDARY outcome

Timeframe: over weeks 12-24

Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=237 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=200 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=218 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=97 Participants Placebo Metered Dose Inhalation
TDI Focal Score Over Weeks 12-24 - Japan Approach - Symptomatic Population	1.5 Scores on a scale Interval 1.2 to 1.8	1.4 Scores on a scale Interval 1.0 to 1.7	1.1 Scores on a scale Interval 0.8 to 1.4	0.7 Scores on a scale Interval 0.2 to 1.2

SECONDARY outcome

Timeframe: at week 24

Peak change from baseline in FEV1 within 2 hours post-dosing at Week 24 US/China approach

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=490 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=413 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=412 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=196 Participants Placebo Metered Dose Inhalation
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing at Week 24 US/China Approach	358 mL Interval 338.0 to 378.0	247 mL Interval 226.0 to 269.0	214 mL Interval 192.0 to 235.0	55 mL Interval 24.0 to 87.0

SECONDARY outcome

Timeframe: over weeks 12-24

Peak change from baseline in FEV1 within 2 hours post-dosing over weeks 12-24 Japan approach

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=516 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=436 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=436 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=205 Participants Placebo Metered Dose Inhalation
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over Weeks 12-24 Japan Approach	368 mL Interval 350.0 to 386.0	255 mL Interval 236.0 to 274.0	228 mL Interval 209.0 to 248.0	70 mL Interval 42.0 to 98.0

SECONDARY outcome

Timeframe: over 24 weeks

Peak change from baseline in FEV1 within 2 hours post-dosing over 24 weeks EU/SK/TW approach

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=550 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=480 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=474 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=235 Participants Placebo Metered Dose Inhalation
Peak Change From Baseline in FEV1 Within 2 Hours Post-dosing Over 24 Weeks EU/SK/TW Approach	375 mL Interval 360.0 to 389.0	277 mL Interval 261.0 to 293.0	234 mL Interval 218.0 to 250.0	82 mL Interval 58.0 to 105.0

SECONDARY outcome

Timeframe: at week 24

Change from baseline in the SGRQ total score. The SGRQ is a disease-specific questionnaire, self-completed by participants, used to evaluate the effect of GFF MDI, FF MDI and GP MDI on health-related quality of life as compared to placebo in subjects with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=489 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=415 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=412 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=196 Participants Placebo Metered Dose Inhalation
Change From Baseline in SGRQ Total Score at Week 24, US/China Approach	-5.3 Scores on a scale Interval -6.4 to -4.2	-5.6 Scores on a scale Interval -6.8 to -4.4	-3.7 Scores on a scale Interval -4.8 to -2.5	-0.9 Scores on a scale Interval -2.6 to 0.8

SECONDARY outcome

Timeframe: over weeks 12-24

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=516 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=436 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=436 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=205 Participants Placebo Metered Dose Inhalation
Change From Baseline in SGRQ Total Score Over Weeks 12-24 , Japan & EU/SK/TW Approach	-5.2 Scores on a scale Interval -6.1 to -4.3	-5.0 Scores on a scale Interval -5.9 to -4.0	-3.6 Scores on a scale Interval -4.6 to -2.6	-1.7 Scores on a scale Interval -3.1 to -0.3

SECONDARY outcome

Timeframe: at week 24

Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2n

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=220 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=189 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=202 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=92 Participants Placebo Metered Dose Inhalation
Change From Baseline in SGRQ Total Score at Week 24 in Symptomatic Population, US/China Approach	-6.9 Scores on a scale Interval -8.6 to -5.2	-7.8 Scores on a scale Interval -9.7 to -5.9	-3.8 Scores on a scale Interval -5.6 to -2.0	-1.6 Scores on a scale Interval -4.3 to 1.1

SECONDARY outcome

Timeframe: over weeks 12-24

Population: Symptomatic Population was defined as all subjects in the ITT Population with CAT scores of ≥15 at Visit 2

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=237 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=200 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=218 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=97 Participants Placebo Metered Dose Inhalation
Change From Baseline in SGRQ Total Score Over Weeks 12-24, in Symptomatic Population, Japan & EU/SK/TW Approach	-6.9 Scores on a scale Interval -8.4 to -5.4	-7.3 Scores on a scale Interval -8.9 to -5.6	-3.9 Scores on a scale Interval -5.5 to -2.4	-3.1 Scores on a scale Interval -5.4 to -0.8

SECONDARY outcome

Timeframe: over 24 weeks

Population: RVU Population - defined as Rescue Ventolin User

Change from baseline in average daily rescue Ventolin use over 24 weeks in RVU population, all approaches

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=256 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=232 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=225 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=109 Participants Placebo Metered Dose Inhalation
Change From Baseline in Average Daily Rescue Ventolin Use Over 24 Weeks in RVU Population, All Approaches	-1.4 Puffs/day Interval -1.7 to -1.1	-1.0 Puffs/day Interval -1.3 to -0.7	-0.6 Puffs/day Interval -0.9 to -0.3	-0.4 Puffs/day Interval -0.8 to 0.0

SECONDARY outcome

Timeframe: Assessed at 5-minutes post dose on Day 1

Onset of Action as Assessed by FEV1 Day 1 at 5 Minutes Post-Dose. Reported is the FEV1 measured at 5 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=464 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=406 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=403 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=197 Participants Placebo Metered Dose Inhalation
FEV1 Measured at 5 Minutes Post-dose on Day 1	0.202 Liters Interval 0.191 to 0.212	0.186 Liters Interval 0.175 to 0.197	0.059 Liters Interval 0.048 to 0.07	0.022 Liters Interval 0.006 to 0.038

SECONDARY outcome

Timeframe: Assessed at 15-minute post dose on Day 1

Onset of Action as Assessed by FEV1 Day 1 at 15 Minutes Post-Dose. Reported is the FEV1 measured at 15 minutes post-dose on Day 1 as the first time point when the difference from Placebo was statistically significant

Outcome measures

Outcome measures
Measure	GFF MDI 14.4/9.6 ug n=530 Participants Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=458 Participants Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=453 Participants Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=229 Participants Placebo Metered Dose Inhalation
FEV1 Measured at 15 Minutes Post-dose on Day 1	0.241 Liters Interval 0.23 to 0.252	0.220 Liters Interval 0.208 to 0.231	0.105 Liters Interval 0.093 to 0.117	0.033 Liters Interval 0.016 to 0.05

Adverse Events

GFF MDI 14.4/9.6 ug

Serious events: 53 serious events

Other events: 166 other events

Deaths: 1 deaths

FF MDI 9.6 ug

Serious events: 40 serious events

Other events: 123 other events

Deaths: 1 deaths

GP MDI 14.4 ug

Serious events: 34 serious events

Other events: 128 other events

Deaths: 1 deaths

Placebo MDI

Serious events: 19 serious events

Other events: 61 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	GFF MDI 14.4/9.6 ug n=551 participants at risk Glycopyrronium, Formoterol Fumarate, Metered Dose Inhalation 14.4/9.6 ug	FF MDI 9.6 ug n=480 participants at risk Formoterol Fumarate, Metered Dose Inhalation 9.6 ug	GP MDI 14.4 ug n=474 participants at risk Glycopyrronium 14.4 ug Metered Dose Inhalation	Placebo MDI n=235 participants at risk Placebo Metered Dose Inhalation
Musculoskeletal and connective tissue disorders Back Pain	2.7% 15/551 • Number of events 16 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.0% 5/480 • Number of events 5 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.5% 7/474 • Number of events 7 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.43% 1/235 • Number of events 1 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Infections and infestations Viral upper respiratory tract infection	9.1% 50/551 • Number of events 56 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	9.6% 46/480 • Number of events 52 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	9.3% 44/474 • Number of events 55 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	6.8% 16/235 • Number of events 17 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Infections and infestations Upper respiratory tract infection	6.7% 37/551 • Number of events 44 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	6.0% 29/480 • Number of events 34 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	7.0% 33/474 • Number of events 40 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	8.5% 20/235 • Number of events 24 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Infections and infestations Pneumonia	1.6% 9/551 • Number of events 9 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.0% 5/480 • Number of events 5 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.1% 5/474 • Number of events 5 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.6% 6/235 • Number of events 6 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Infections and infestations Bronchitis	0.73% 4/551 • Number of events 5 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.2% 6/480 • Number of events 7 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.7% 8/474 • Number of events 8 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.1% 5/235 • Number of events 5 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.
Infections and infestations Pharyngitis	2.0% 11/551 • Number of events 11 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.83% 4/480 • Number of events 4 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.63% 3/474 • Number of events 3 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.00% 0/235 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. 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 Chronic obstructive pulmonary disease	2.9% 16/551 • Number of events 16 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.7% 13/480 • Number of events 13 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.5% 12/474 • Number of events 12 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	3.0% 7/235 • Number of events 7 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. 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 Cough	2.4% 13/551 • Number of events 14 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.7% 8/480 • Number of events 8 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	2.1% 10/474 • Number of events 11 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	0.85% 2/235 • Number of events 3 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. 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 Dyspnoea	2.0% 11/551 • Number of events 11 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.5% 7/480 • Number of events 7 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	1.3% 6/474 • Number of events 8 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.	3.0% 7/235 • Number of events 7 • Adverse events were collected from the time the subject signed consent throughout the four treatment periods of 24 weeks and up to 10 days following the last dose of study drug. The Safety Population was defined as all subjects who were randomized to treatment regardless and received at least one dose of study treatment. Serious adverse events collected from the time the subject signed consent up to 14 days following the last dose of study drug.

Additional Information

Pearl Therapeutics Inc.

Phone: 650-305-2600

Email: [email protected]

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