Trial Outcomes & Findings for Efficacy and Safety Study of PT009, PT008, and PT005 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02196077)

NCT ID: NCT02196077

Last Updated: 2018-06-20

Results Overview

Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 180 participants
• Primary outcome timeframe: Day 29
• Results posted on: 2018-06-20

Participant Flow

This study was conducted at 20 sites in the United States from August 2014 to March 2015. Study participation was a maximum of 28 days.

A Randomized, Double-Blind, Chronic Dosing (28 Days), Four-Period, Five-Treatment, Incomplete Block, Multi-Center, Crossover Study. Subjects completed final visit procedures. Final telephone follow-up occurred between 7 to 14 days from Visit 13. By-sequence tabulations of the data were not pre-specified.

Participant milestones

Measure	Subjects
Overall Study STARTED	180
Overall Study BFF MDI 320/9.6 μg	155
Overall Study BFF MDI 160/9.6 μg	106
Overall Study BFF MDI 80/9.6 μg	103
Overall Study BD MDI 320 μg	108
Overall Study FF MDI 9.6 μg	157
Overall Study COMPLETED	133
Overall Study NOT COMPLETED	47

Reasons for withdrawal

Measure	Subjects
Overall Study Adverse Event	4
Overall Study Lack of Efficacy	1
Overall Study Withdrawal by Subject	14
Overall Study Physician Decision	1
Overall Study Lost to Follow-up	3
Overall Study Protocol Violation	24

Baseline Characteristics

Efficacy and Safety Study of PT009, PT008, and PT005 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Measure	Subjects n=180 Participants
Age, Continuous	62.2 Years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	96 Participants n=5 Participants
Sex: Female, Male Male	84 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 29

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.

Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)

Outcome measures

Measure	BFF MDI 320/9.6 ug n=148 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=98 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=96 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=99 Participants BD MDI 320 ug	FF MDI 9.6 ug n=142 Participants FF MDI 9.6 ug
FEV1 AUC0-12 on Day 29	0.231 Liters Interval 0.197 to 0.266	0.197 Liters Interval 0.158 to 0.236	0.205 Liters Interval 0.165 to 0.244	0.011 Liters Interval -0.028 to 0.05	0.176 Liters Interval 0.141 to 0.21

SECONDARY outcome

Timeframe: Over 28 days

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=151 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=100 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=97 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=102 Participants BD MDI 320 ug	FF MDI 9.6 ug n=147 Participants FF MDI 9.6 ug
Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days	0.138 Liters Interval 0.111 to 0.165	0.121 Liters Interval 0.089 to 0.153	0.110 Liters Interval 0.078 to 0.142	0.022 Liters Interval -0.009 to 0.054	0.083 Liters Interval 0.056 to 0.11

SECONDARY outcome

Timeframe: Day 15

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=151 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=100 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=97 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=101 Participants BD MDI 320 ug	FF MDI 9.6 ug n=146 Participants FF MDI 9.6 ug
Peak Change From Baseline in FEV1 (in Liters) Day 15	0.388 Liters Interval 0.354 to 0.422	0.366 Liters Interval 0.327 to 0.405	0.348 Liters Interval 0.308 to 0.387	0.143 Liters Interval 0.104 to 0.182	0.320 Liters Interval 0.286 to 0.354

SECONDARY outcome

Timeframe: Day 29

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=148 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=98 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=96 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=99 Participants BD MDI 320 ug	FF MDI 9.6 ug n=142 Participants FF MDI 9.6 ug
Peak Change From Baseline in FEV1 (in Liters) Day 29	0.390 Liters Interval 0.356 to 0.424	0.356 Liters Interval 0.317 to 0.395	0.359 Liters Interval 0.319 to 0.398	0.138 Liters Interval 0.099 to 0.177	0.322 Liters Interval 0.287 to 0.356

SECONDARY outcome

Timeframe: Day 1

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=151 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=100 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=97 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=104 Participants BD MDI 320 ug	FF MDI 9.6 ug n=148 Participants FF MDI 9.6 ug
Peak Change From Baseline in FEV1 on Day 1	0.338 Liters Interval 0.304 to 0.372	0.310 Liters Interval 0.271 to 0.349	0.314 Liters Interval 0.275 to 0.354	0.096 Liters Interval 0.058 to 0.135	0.313 Liters Interval 0.279 to 0.347

SECONDARY outcome

Timeframe: Day 29

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=148 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=98 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=96 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=99 Participants BD MDI 320 ug	FF MDI 9.6 ug n=142 Participants FF MDI 9.6 ug
Forced Vital Capacity (FVC) AUC0-12 on Day 29	0.305 Liters Interval 0.244 to 0.365	0.245 Liters Interval 0.176 to 0.315	0.267 Liters Interval 0.196 to 0.337	0.002 Liters Interval -0.068 to 0.071	0.253 Liters Interval 0.191 to 0.314

SECONDARY outcome

Timeframe: Day 29

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.

Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)

Outcome measures

Measure	BFF MDI 320/9.6 ug n=149 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=97 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=96 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=100 Participants BD MDI 320 ug	FF MDI 9.6 ug n=142 Participants FF MDI 9.6 ug
Transition Dyspnea Index (TDI) Focal Score on Day 29	0.598 Index Interval 0.298 to 0.899	0.882 Index Interval 0.518 to 1.246	0.459 Index Interval 0.093 to 0.825	-0.109 Index Interval -0.468 to 0.25	0.260 Index Interval -0.047 to 0.566

SECONDARY outcome

Timeframe: Visit 12-13 (7 days)

Population: MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods

Outcome measures

Measure	BFF MDI 320/9.6 ug n=152 Participants BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=101 Participants BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=98 Participants BFF MDI 80/9.6 ug	BD MDI 320 ug n=104 Participants BD MDI 320 ug	FF MDI 9.6 ug n=149 Participants FF MDI 9.6 ug
Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment	0.05 Puffs Interval -0.34 to 0.43	0.16 Puffs Interval -0.27 to 0.58	0.24 Puffs Interval -0.19 to 0.67	0.96 Puffs Interval 0.54 to 1.38	0.44 Puffs Interval 0.06 to 0.83

Adverse Events

BFF MDI 320/9.6 ug

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

BFF MDI 160/9.6 ug

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

BFF MDI 80/9.6 ug

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

BD MDI 320 ug

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

FF MDI 9.6 ug

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	BFF MDI 320/9.6 ug n=155 participants at risk BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=106 participants at risk BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=103 participants at risk BFF MDI 80/9.6 ug	BD MDI 320 ug n=108 participants at risk BD MDI 320 ug	FF MDI 9.6 ug n=157 participants at risk FF MDI 9.6 ug
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.65% 1/155 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	1.9% 2/108 • Number of events 2 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Respiratory, thoracic and mediastinal disorders Laryngeal Oedema	0.65% 1/155 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Cardiac disorders Angina Pectoris	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Cardiac disorders Coronary Artery Disease	0.65% 1/155 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Infections and infestations Appendicitis	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.64% 1/157 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Infections and infestations Clostridium Difficile Colitis	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.93% 1/108 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Infections and infestations Gastroenteritis	0.65% 1/155 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.93% 1/108 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Nervous system disorders Cerebrovascular Accident	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Psychiatric disorders Anxiety	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.64% 1/157 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.94% 1/106 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.93% 1/108 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Gastrointestinal disorders Small Intestinal Obstruction	0.00% 0/155 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.94% 1/106 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/103 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.

Other adverse events

Measure	BFF MDI 320/9.6 ug n=155 participants at risk BFF MDI 320/9.6 ug	BFF MDI 160/9.6 ug n=106 participants at risk BFF MDI 160/9.6 ug	BFF MDI 80/9.6 ug n=103 participants at risk BFF MDI 80/9.6 ug	BD MDI 320 ug n=108 participants at risk BD MDI 320 ug	FF MDI 9.6 ug n=157 participants at risk FF MDI 9.6 ug
Infections and infestations Nasopharyngitis	3.2% 5/155 • Number of events 5 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.94% 1/106 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	1.9% 2/103 • Number of events 2 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	1.9% 2/108 • Number of events 2 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	3.2% 5/157 • Number of events 5 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Cardiac disorders Hypertension	1.3% 2/155 • Number of events 2 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.94% 1/106 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	2.8% 3/108 • Number of events 3 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	1.3% 2/157 • Number of events 2 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Respiratory, thoracic and mediastinal disorders Cough	0.65% 1/155 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	2.8% 3/108 • Number of events 3 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.64% 1/157 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.
Infections and infestations Upper Respiratory Tract Infection	2.6% 4/155 • Number of events 4 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/106 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.97% 1/103 • Number of events 1 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/108 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.	0.00% 0/157 • AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose. The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.

Additional Information

Paul Dorinsky, MD, FCCP

Pearl Therapeutics Inc.

Phone: 650-305-2600

Email: pdorinsky@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 its opinions, or the opinions of the publication committee, if these differ with the proposed publication.
• Publication restrictions are in place

Restriction type: OTHER