Trial Outcomes & Findings for 7 Days of TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease (NCT NCT01704404)

NCT ID: NCT01704404

Last Updated: 2022-02-24

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 62 participants
• Primary outcome timeframe: From baseline to day 7
• Results posted on: 2022-02-24

Participant Flow

Participant milestones

Measure	Treatment 1 Placebo, 44 µg, 88 µg, 350 µg, 700 µg	Treatment 2 Placebo, 22 µg, 88 µg, 350 µg, 700 µg	Treatment 3 Placebo, 22 µg, 88 µg, 175 µg, 700 µg	Treatment 4 22 µg, 44 µg, 175 µg, 700 µg	Treatment 5 22 µg, 44 µg, 175 µg, 350 µg	Treatment 6 Placebo, 44 µg, 88 µg, 175 µg, 350 µg
Overall Study STARTED	11	10	10	11	11	9
Overall Study COMPLETED	10	9	9	8	10	9
Overall Study NOT COMPLETED	1	1	1	3	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

7 Days of TD-4208 in Subjects With Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	Entire Study Population n=62 Participants All subjects received Placebo and 4 of 6 TD-4208 dose levels: TD-4208 - 22 µg TD-4208 - 44 µg TD-4208 - 88 µg TD-4208 - 175 µg TD-4208 - 350 µg TD-4208 - 700 µg
Age, Continuous	64.2 year STANDARD_DEVIATION 6.80 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to day 7

Outcome measures

Measure	Dose 1 TD-4208 n=40 Participants 22 µg TD-4208	Dose 2 TD-4208 n=39 Participants 44 µg TD-4208	Dose 3 TD-4208 n=39 Participants 88 µg TD-4208	Dose 4 TD-4208 n=39 Participants 175 µg TD-4208	Dose 5 TD-4208 n=39 Participants 350 µg TD-4208	Dose 6 TD-4208 n=40 Participants 700 µg TD-4208	Placebo n=59 Participants Placebo Placebo
Change From Baseline to Day 7 in Trough FEV1 (Forced Expiratory Volume in 1 Second)	91.2 FEV1 (mL) Standard Error 19.21	92.8 FEV1 (mL) Standard Error 20.25	113.1 FEV1 (mL) Standard Error 19.55	151.9 FEV1 (mL) Standard Error 19.99	132.2 FEV1 (mL) Standard Error 19.02	119.4 FEV1 (mL) Standard Error 19.54	37.8 FEV1 (mL) Standard Error 16.93

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to day 7

Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

Outcome measures

Measure	Dose 1 TD-4208 n=37 Participants 22 µg TD-4208	Dose 2 TD-4208 n=36 Participants 44 µg TD-4208	Dose 3 TD-4208 n=35 Participants 88 µg TD-4208	Dose 4 TD-4208 n=35 Participants 175 µg TD-4208	Dose 5 TD-4208 n=40 Participants 350 µg TD-4208	Dose 6 TD-4208 n=35 Participants 700 µg TD-4208	Placebo Placebo Placebo
Cmax	.0125 ng/mL Standard Deviation .00627	.0224 ng/mL Standard Deviation .00864	.0526 ng/mL Standard Deviation .0214	.114 ng/mL Standard Deviation .0488	.243 ng/mL Standard Deviation .104	.577 ng/mL Standard Deviation .261	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to day 7

Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

Outcome measures

Measure	Dose 1 TD-4208 n=37 Participants 22 µg TD-4208	Dose 2 TD-4208 n=36 Participants 44 µg TD-4208	Dose 3 TD-4208 n=35 Participants 88 µg TD-4208	Dose 4 TD-4208 n=35 Participants 175 µg TD-4208	Dose 5 TD-4208 n=40 Participants 350 µg TD-4208	Dose 6 TD-4208 n=35 Participants 700 µg TD-4208	Placebo Placebo Placebo
Tmax	.233 hours Standard Deviation .217	.233 hours Standard Deviation 0.200	0.233 hours Standard Deviation 0.200	0.233 hours Standard Deviation 0.200	0.233 hours Standard Deviation 0.217	0.233 hours Standard Deviation 0.200	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From baseline to day 7

Population: The number of subjects reported for plasma half lives are based on the actual evaluable PK data.

Day 1: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, and 6 hours.

Day 7: 15 minutes pre-dose, post-dose at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours.

Outcome measures

Measure	Dose 1 TD-4208 22 µg TD-4208	Dose 2 TD-4208 44 µg TD-4208	Dose 3 TD-4208 88 µg TD-4208	Dose 4 TD-4208 175 µg TD-4208	Dose 5 TD-4208 n=31 Participants 350 µg TD-4208	Dose 6 TD-4208 n=26 Participants 700 µg TD-4208	Placebo Placebo Placebo
Plasma Half-life	—	—	—	—	25.1 hours Standard Deviation 7.89	23.0 hours Standard Deviation 7.05	—

Adverse Events

Dose 1 TD-4208

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Dose 2 TD-4208

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Dose 3 TD-4208

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Dose 4 TD-4208

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Dose 5 TD-4208

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Dose 6 TD-4208

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dose 1 TD-4208 n=41 participants at risk；n=42 participants at risk 22 µg TD-4208	Dose 2 TD-4208 n=39 participants at risk；n=42 participants at risk 44 µg TD-4208	Dose 3 TD-4208 n=40 participants at risk 88 µg TD-4208	Dose 4 TD-4208 n=37 participants at risk；n=41 participants at risk 175 µg TD-4208	Dose 5 TD-4208 n=41 participants at risk 350 µg TD-4208	Dose 6 TD-4208 n=37 participants at risk；n=42 participants at risk 700 µg TD-4208	Placebo n=61 participants at risk；n=62 participants at risk Placebo Placebo
General disorders Chest Pain	2.4% 1/42 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/62 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Nervous system disorders Transient Ischaemic Attack	2.4% 1/42 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/62 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Infections and infestations Pneumonia	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/42 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	1.6% 1/62 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.

Other adverse events

Measure	Dose 1 TD-4208 n=41 participants at risk；n=42 participants at risk 22 µg TD-4208	Dose 2 TD-4208 n=39 participants at risk；n=42 participants at risk 44 µg TD-4208	Dose 3 TD-4208 n=40 participants at risk 88 µg TD-4208	Dose 4 TD-4208 n=37 participants at risk；n=41 participants at risk 175 µg TD-4208	Dose 5 TD-4208 n=41 participants at risk 350 µg TD-4208	Dose 6 TD-4208 n=37 participants at risk；n=42 participants at risk 700 µg TD-4208	Placebo n=61 participants at risk；n=62 participants at risk Placebo Placebo
Nervous system disorders Headache	7.3% 3/41 • Number of events 3 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.1% 2/39 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	7.5% 3/40 • Number of events 3 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	10.8% 4/37 • Number of events 4 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	7.3% 3/41 • Number of events 3 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	13.5% 5/37 • Number of events 5 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	14.8% 9/61 • Number of events 9 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Respiratory, thoracic and mediastinal disorders Cough	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.6% 1/39 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.0% 2/40 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.4% 2/37 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.4% 2/37 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	1.6% 1/61 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 1/41 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.6% 1/39 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.5% 1/40 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.4% 2/37 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.7% 1/37 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	6.6% 4/61 • Number of events 4 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Musculoskeletal and connective tissue disorders Back Pain	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/39 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.5% 1/40 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.7% 1/37 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.4% 1/41 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Skin and subcutaneous tissue disorders Rash	2.4% 1/41 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.6% 1/39 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.4% 2/37 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.7% 1/37 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Respiratory, thoracic and mediastinal disorders COPD	2.4% 1/41 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/39 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	7.5% 3/40 • Number of events 3 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
General disorders Fatigue	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.1% 2/39 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Gastrointestinal disorders Nausea	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.1% 2/39 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.7% 1/37 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	1.6% 1/61 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Injury, poisoning and procedural complications Contusion	4.9% 2/41 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.6% 1/39 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Vascular disorders Haematoma	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/39 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.0% 2/40 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	1.6% 1/61 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	5.1% 2/39 • Number of events 2 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/40 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	2.7% 1/37 • Number of events 1 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/41 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/37 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.	0.00% 0/61 • 13 weeks The Participant Flow shows the # of subjs in each of the 6 treatment sequences (each sequence has 4 treatments; 4/6 study drug doses and placebo) as instructed by CTgov for complex crossover designs. The Number of Participants at Risk, instead, shows the # of subjs exposed to each of the 6 doses of study drug and placebo. Also, some subjs did not complete all of the doses in their treatment sequence. The # of subjs in each sequence is not related to the # of subjs in each dose level therefore.

Additional Information

Head of Clinical Development & Medical Affairs

Theravance Biopharma

Phone: 1-855-633-8479

Email: medinfo@theravance.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER