Trial Outcomes & Findings for Steroids In Eosinophil Negative Asthma (NCT NCT02066298)

NCT ID: NCT02066298

Last Updated: 2019-05-29

Results Overview

This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of treatment failures. If one treatment results in no treatment failures and another treatment does, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by treatment failures, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 295 participants
• Primary outcome timeframe: End of 12-week treatment period
• Results posted on: 2019-05-29

Participant Flow

Participant milestones

Measure	Mometasone Then Tiotropium Then Placebo Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Mometasone Then Placebo Then Tiotropium Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Mometasone Then Tiotropium Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Tiotropium Then Mometasone Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Placebo Then Mometasone Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Mometasone Then Placebo Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo
Overall Study STARTED	49	48	50	51	47	50
Overall Study Completed 1st Period	44	47	45	48	46	45
Overall Study Completed 2nd Period	41	41	41	46	42	41
Overall Study Completed 3rd Period	40	40	40	45	38	38
Overall Study COMPLETED	40	40	40	45	38	38
Overall Study NOT COMPLETED	9	8	10	6	9	12

Reasons for withdrawal

Measure	Mometasone Then Tiotropium Then Placebo Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Mometasone Then Placebo Then Tiotropium Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Mometasone Then Tiotropium Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Tiotropium Then Mometasone Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Placebo Then Mometasone Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Mometasone Then Placebo Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo
Overall Study Lost to Follow-up	3	2	3	2	3	4
Overall Study Withdrawal by Subject	6	6	6	4	5	8
Overall Study Physician Decision	0	0	1	0	1	0

Baseline Characteristics

Steroids In Eosinophil Negative Asthma

Baseline characteristics by cohort

Measure	Mometasone Then Tiotropium Then Placebo n=49 Participants Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Mometasone Then Placebo Then Tiotropium n=48 Participants Mometasone 220mcg BID, followed by Placebo, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Mometasone Then Tiotropium n=50 Participants Placebo, followed by Mometasone 220mcg BID, followed by Tiotropium Respimat 5mcg QD Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Placebo Then Tiotropium Then Mometasone n=51 Participants Placebo, followed by Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Placebo Then Mometasone n=47 Participants Tiotropium Respimat 5mcg QD, followed by Placebo, followed by Mometasone 220mcg BID Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Tiotropium Then Mometasone Then Placebo n=50 Participants Tiotropium Respimat 5mcg QD, followed by Mometasone 220mcg BID, followed by Placebo Mometasone 220mcg BID: Mometasone is an ICS Tiotropium Respimat 5mcg QD: Tiotropium is a LMA Placebo	Total n=295 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants	44 Participants n=7 Participants	46 Participants n=5 Participants	44 Participants n=4 Participants	40 Participants n=21 Participants	43 Participants n=8 Participants	260 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Continuous	32.3 years STANDARD_DEVIATION 15.3 • n=5 Participants	32.6 years STANDARD_DEVIATION 13.8 • n=7 Participants	33.2 years STANDARD_DEVIATION 13.9 • n=5 Participants	30.0 years STANDARD_DEVIATION 14.8 • n=4 Participants	30.8 years STANDARD_DEVIATION 12.5 • n=21 Participants	28.2 years STANDARD_DEVIATION 12.9 • n=8 Participants	31.2 years STANDARD_DEVIATION 13.9 • n=8 Participants
Sex: Female, Male Female	29 Participants n=5 Participants	30 Participants n=7 Participants	32 Participants n=5 Participants	33 Participants n=4 Participants	27 Participants n=21 Participants	33 Participants n=8 Participants	184 Participants n=8 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	20 Participants n=21 Participants	17 Participants n=8 Participants	111 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants	7 Participants n=21 Participants	7 Participants n=8 Participants	35 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	11 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	14 Participants n=7 Participants	15 Participants n=5 Participants	16 Participants n=4 Participants	14 Participants n=21 Participants	16 Participants n=8 Participants	88 Participants n=8 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants	32 Participants n=7 Participants	33 Participants n=5 Participants	31 Participants n=4 Participants	32 Participants n=21 Participants	30 Participants n=8 Participants	192 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	4 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Region of Enrollment United States	49 participants n=5 Participants	48 participants n=7 Participants	50 participants n=5 Participants	51 participants n=4 Participants	47 participants n=21 Participants	50 participants n=8 Participants	295 participants n=8 Participants
Forced expiratory volume at one second (FEV1) Percent of Predicted	90.6 percentage of predicted FEV1 STANDARD_DEVIATION 11.5 • n=5 Participants	91.5 percentage of predicted FEV1 STANDARD_DEVIATION 11.2 • n=7 Participants	92.0 percentage of predicted FEV1 STANDARD_DEVIATION 11.8 • n=5 Participants	93.8 percentage of predicted FEV1 STANDARD_DEVIATION 12.4 • n=4 Participants	91.7 percentage of predicted FEV1 STANDARD_DEVIATION 13.6 • n=21 Participants	91.6 percentage of predicted FEV1 STANDARD_DEVIATION 12.5 • n=8 Participants	91.9 percentage of predicted FEV1 STANDARD_DEVIATION 12.1 • n=8 Participants
Asthma Control Test	21.3 units on a scale STANDARD_DEVIATION 2.3 • n=5 Participants	21.2 units on a scale STANDARD_DEVIATION 2.5 • n=7 Participants	21.1 units on a scale STANDARD_DEVIATION 2.7 • n=5 Participants	20.9 units on a scale STANDARD_DEVIATION 2.2 • n=4 Participants	20.9 units on a scale STANDARD_DEVIATION 2.8 • n=21 Participants	21.1 units on a scale STANDARD_DEVIATION 2.5 • n=8 Participants	21.1 units on a scale STANDARD_DEVIATION 2.5 • n=8 Participants
Sputum differential count - Percent eosinophils	0.1 percentage of cells n=5 Participants	0.4 percentage of cells n=7 Participants	0.4 percentage of cells n=5 Participants	0.2 percentage of cells n=4 Participants	0.2 percentage of cells n=21 Participants	0.2 percentage of cells n=8 Participants	0.2 percentage of cells n=8 Participants
Blood differential count - Percent eosinophils	2.3 percentage of cells n=5 Participants	4.0 percentage of cells n=7 Participants	3.0 percentage of cells n=5 Participants	3.2 percentage of cells n=4 Participants	3.0 percentage of cells n=21 Participants	2.8 percentage of cells n=8 Participants	3.0 percentage of cells n=8 Participants

PRIMARY outcome

Timeframe: End of 12-week treatment period

Population: For each pairwise comparison (mometasone vs. placebo and tiotropium vs. placebo), participants were required to complete both of the relevant treatment periods in order to be included in the analysis.

This composite outcome uses a hierarchical method to ascertain differences in asthma control. For each participant, treatments are first compared to see if they differ in terms of treatment failures. If one treatment results in no treatment failures and another treatment does, it is deemed the superior treatment and no further comparisons are made. If treatment superiority cannot be assigned by treatment failures, then they are compared by asthma control days (ACDs). If one treatment yields at least 31 annualized ACDs more than another, it is deemed the superior treatment. If treatment superiority still cannot be assigned by ACDs, then they are compared by percent predicted FEV1 at the end of a treatment period. If one treatment yields at least 5% greater FEV1 than another, it is deemed the superior treatment. If treatment superiority cannot be assigned by exacerbations, ACDs or FEV1, then that participant is classified as having no differential response.

Outcome measures

Measure	Eosinophil Low n=184 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=67 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Mometesone superior to placebo	74 Participants	35 Participants	—
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Placebo superior to mometasone	56 Participants	12 Participants	—
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Mometesone equal to placebo	46 Participants	20 Participants	—
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Tiotropium superior to placebo	80 Participants	25 Participants	—
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Placebo superior to tiotropium	52 Participants	19 Participants	—
Pairwise Comparison of Treatments Based on Composite Measure Using Treatment Failures, Asthma Control Days, and Percent Predicted FEV1. Tiotropium equal to placebo	49 Participants	18 Participants	—

SECONDARY outcome

Timeframe: End of 12-week treatment period

Population: participants who completed the treatment period with data to evaluate treatment failure outcome

Treatment Failure includes:

• Awakening from asthma three or more times in a two-week period or on two consecutive nights, or
• Using albuterol for relief of symptoms four or more times/day for two or more consecutive days, or
• Albuterol has been relieving symptoms for less than four hours after each treatment over a 12-hour period, or
• Using albuterol for relief of symptoms daily for seven days, and this use exceeds two times the weekly use of albuterol in the baseline period, or
• exercise induces unusual breathlessness

Outcome measures

Measure	Eosinophil Low n=254 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=255 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD n=258 Participants The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Treatment Failure	29 Participants	29 Participants	35 Participants

SECONDARY outcome

Timeframe: End of 12-week treatment period

Population: participants who completed the treatment period with data to evaluate asthma control days

Asthma Control Days (ACD) are based on patient completed electronic daily diaries, and are defined as: A day with no rescue albuterol use (pre-exercise albuterol will not be counted), no non-study asthma medications, no daytime asthma symptoms (shortness of breath, wheezing, chest tightness, phlegm/mucus rated as mild, moderate or severe, or cough rated as moderate or severe), no nighttime asthma symptoms, no unscheduled healthcare visits for asthma, and no PEF < 80% of predetermined baseline. Annualized ACD are calculated as the proportion of ACD during the treatment period multiplied by 365.

Outcome measures

Measure	Eosinophil Low n=216 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=225 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD n=228 Participants The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Annualized Asthma Control Days	179 days Standard Deviation 137	186 days Standard Deviation 141	176 days Standard Deviation 139

SECONDARY outcome

Timeframe: End of 12-week treatment period

Population: participants who completed the treatment period and were able to provide FEV1 measurements

FEV1, expressed as percent of predicted FEV1 based on age, sex, race, and height.

Outcome measures

Measure	Eosinophil Low n=254 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=247 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD n=252 Participants The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Forced Expiratory Volume at One Second (FEV1) Percent of Predicted	92 percentage of predicted FEV1 Standard Deviation 14	94 percentage of predicted FEV1 Standard Deviation 13	95 percentage of predicted FEV1 Standard Deviation 14

SECONDARY outcome

Timeframe: End of 12-week treatment period

Population: participants who completed the treatment period and were able to provide FEV1 measurements

Peak expiratory flow rate is a person's maximum speed of expiration. It measures the airflow through the bronchi and thus the degree of obstruction in the airways.

Outcome measures

Measure	Eosinophil Low n=253 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=249 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD n=256 Participants The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Peak Expiratory Flow Rate	476 liters per minute Standard Deviation 117	485 liters per minute Standard Deviation 117	497 liters per minute Standard Deviation 117

SECONDARY outcome

Timeframe: End of 12-week treatment period

Population: participants who completed the treatment period with data to evaluate exacerbations

Asthma exacerbations are more severe episodes of acute worsening, defined by meeting one or more of the following:

• FEV1 <50% of baseline on 2 consecutive measurements
• FEV1 <40% of predicted on 2 consecutive measurements
• Use of ≥ 16 puffs of "as needed" β-agonist per 24 hours for a period of 48 hours
• Use of oral/parenteral corticosteroid due to asthma

Outcome measures

Measure	Eosinophil Low n=254 Participants Participants with sputum eosinophils \< 2% at study entry	Eosinophil High n=255 Participants Participants with sputum eosinophils \>= 2% at study entry	Tiotropium Respimat 5mcg QD n=258 Participants The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Asthma Exacerbations	1 Participants	3 Participants	5 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Mometasone 220mcg BID

Serious events: 6 serious events

Other events: 47 other events

Deaths: 0 deaths

Tiotropium Respimat 5mcg QD

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=276 participants at risk The placebo treatment period for all participants	Mometasone 220mcg BID n=275 participants at risk The mometasone treatment period for all participants. Mometasone administered 220mcg BID	Tiotropium Respimat 5mcg QD n=271 participants at risk The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Pregnancy, puerperium and perinatal conditions pregnancy	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Musculoskeletal and connective tissue disorders closed fracture of lower end of humerus	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Gastrointestinal disorders Partial bowel obstruction.	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/275 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.37% 1/271 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hydatidiform mole	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/275 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.37% 1/271 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Psychiatric disorders Unspecified nonpsychotic mental disorder	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Psychiatric disorders Adjustment disorder with depressed mood	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignant neoplasm of skin of other and unspecified parts of face	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Gastrointestinal disorders Acute appendicitis without mention of peritonitis	0.00% 0/276 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.36% 1/275 • Number of events 1 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	0.00% 0/271 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.

Other adverse events

Measure	Placebo n=276 participants at risk The placebo treatment period for all participants	Mometasone 220mcg BID n=275 participants at risk The mometasone treatment period for all participants. Mometasone administered 220mcg BID	Tiotropium Respimat 5mcg QD n=271 participants at risk The tiotropium treatment period for all participants. Tiotropium administered 5mcg QD
Respiratory, thoracic and mediastinal disorders Acute nasopharyngitis	13.4% 37/276 • Number of events 42 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	12.0% 33/275 • Number of events 38 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	10.7% 29/271 • Number of events 37 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.
Respiratory, thoracic and mediastinal disorders Acute URI not otherwise specified	2.9% 8/276 • Number of events 9 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	5.8% 16/275 • Number of events 18 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.	4.1% 11/271 • Number of events 13 • Each participant was followed over the course of three 12-week treatment periods for a total of 36 weeks. The adverse events recorded below are reported at the treatment period level and represent 12 weeks of "at risk" exposure time.

Additional Information

David Mauger

Penn State University

Phone: 717-531-7178

Email: dmauger@psu.edu

Results disclosure agreements

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