Trial Outcomes & Findings for Efficacy and Safety of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistant Asthma (NCT NCT03358147)

Last Updated: 2020-08-12

Results Overview

Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4)AUC was normalized for length of follow up (e.g. typically 4 hours).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

1077 participants

Primary outcome timeframe

Week 24

Results posted on

2020-08-12

Participant Flow

The study randomized subjects at 194 sites in the United States from December 2017 to September 2019. The entire study period was scheduled to take up to approximately 26 weeks for each individual subject from the time of screening through the follow up period.

Subjects were randomized in a 2:2:2:2:1 Scheme to follow 1 of the 5 treatment groups.

Participant milestones

Participant milestones
Measure	GP MDI 28.8 μg Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg Spiriva Respimat 2.5 μg
Overall Study STARTED	235	240	240	237	119
Overall Study COMPLETED	201	201	206	201	105
Overall Study NOT COMPLETED	34	39	34	36	14

Reasons for withdrawal

Reasons for withdrawal
Measure	GP MDI 28.8 μg Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg Spiriva Respimat 2.5 μg
Overall Study Withdrawal by Subject	13	19	16	10	5
Overall Study Adverse Event	3	9	7	5	2
Overall Study Lost to Follow-up	4	3	7	6	4
Overall Study Major Protocol Deviation	11	3	2	3	1
Overall Study Protocol specified criteria	2	3	0	3	1
Overall Study Physician Decision	1	0	1	6	1
Overall Study Administrative reasons	0	1	0	3	0
Overall Study Lack of Efficacy	0	1	1	0	0

Baseline Characteristics

Safety Population

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GP MDI 28.8 μg n=235 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=240 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=240 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=237 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=119 Participants Spiriva Respimat 2.5 μg	Total n=1071 Participants Total of all reporting groups
Age, Continuous	48.4 Years STANDARD_DEVIATION 15.1 • n=5 Participants • Safety Population	47.7 Years STANDARD_DEVIATION 16.8 • n=7 Participants • Safety Population	46.7 Years STANDARD_DEVIATION 15.5 • n=5 Participants • Safety Population	47.1 Years STANDARD_DEVIATION 16.2 • n=4 Participants • Safety Population	49.8 Years STANDARD_DEVIATION 15.3 • n=21 Participants • Safety Population	47.7 Years STANDARD_DEVIATION 15.8 • n=10 Participants • Safety Population
Sex: Female, Male Female	146 Participants n=5 Participants • Safety Population	153 Participants n=7 Participants • Safety Population	151 Participants n=5 Participants • Safety Population	134 Participants n=4 Participants • Safety Population	76 Participants n=21 Participants • Safety Population	660 Participants n=10 Participants • Safety Population
Sex: Female, Male Male	89 Participants n=5 Participants • Safety Population	87 Participants n=7 Participants • Safety Population	89 Participants n=5 Participants • Safety Population	103 Participants n=4 Participants • Safety Population	43 Participants n=21 Participants • Safety Population	411 Participants n=10 Participants • Safety Population
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants • Safety Population	61 Participants n=7 Participants • Safety Population	52 Participants n=5 Participants • Safety Population	51 Participants n=4 Participants • Safety Population	21 Participants n=21 Participants • Safety Population	221 Participants n=10 Participants • Safety Population
Ethnicity (NIH/OMB) Not Hispanic or Latino	198 Participants n=5 Participants • Safety Population	179 Participants n=7 Participants • Safety Population	186 Participants n=5 Participants • Safety Population	186 Participants n=4 Participants • Safety Population	98 Participants n=21 Participants • Safety Population	847 Participants n=10 Participants • Safety Population
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants • Safety Population	0 Participants n=7 Participants • Safety Population	2 Participants n=5 Participants • Safety Population	0 Participants n=4 Participants • Safety Population	0 Participants n=21 Participants • Safety Population	3 Participants n=10 Participants • Safety Population
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • Safety Population	1 Participants n=7 Participants • Safety Population	3 Participants n=5 Participants • Safety Population	0 Participants n=4 Participants • Safety Population	1 Participants n=21 Participants • Safety Population	5 Participants n=10 Participants • Safety Population
Race (NIH/OMB) Asian	6 Participants n=5 Participants • Safety Population	1 Participants n=7 Participants • Safety Population	6 Participants n=5 Participants • Safety Population	2 Participants n=4 Participants • Safety Population	0 Participants n=21 Participants • Safety Population	15 Participants n=10 Participants • Safety Population
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants • Safety Population	0 Participants n=7 Participants • Safety Population	0 Participants n=5 Participants • Safety Population	0 Participants n=4 Participants • Safety Population	0 Participants n=21 Participants • Safety Population	1 Participants n=10 Participants • Safety Population
Race (NIH/OMB) Black or African American	62 Participants n=5 Participants • Safety Population	68 Participants n=7 Participants • Safety Population	52 Participants n=5 Participants • Safety Population	52 Participants n=4 Participants • Safety Population	25 Participants n=21 Participants • Safety Population	259 Participants n=10 Participants • Safety Population
Race (NIH/OMB) White	165 Participants n=5 Participants • Safety Population	168 Participants n=7 Participants • Safety Population	177 Participants n=5 Participants • Safety Population	179 Participants n=4 Participants • Safety Population	93 Participants n=21 Participants • Safety Population	782 Participants n=10 Participants • Safety Population
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • Safety Population	0 Participants n=7 Participants • Safety Population	0 Participants n=5 Participants • Safety Population	0 Participants n=4 Participants • Safety Population	0 Participants n=21 Participants • Safety Population	0 Participants n=10 Participants • Safety Population
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants • Safety Population	2 Participants n=7 Participants • Safety Population	2 Participants n=5 Participants • Safety Population	4 Participants n=4 Participants • Safety Population	0 Participants n=21 Participants • Safety Population	9 Participants n=10 Participants • Safety Population

PRIMARY outcome

Timeframe: Week 24

Population: mITT Population

Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4)AUC was normalized for length of follow up (e.g. typically 4 hours).

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=195 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=199 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=205 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=196 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=103 Participants Spiriva Respimat 2.5 μg
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4)	0.294 Liter Interval 0.248 to 0.341	0.284 Liter Interval 0.238 to 0.331	0.308 Liter Interval 0.263 to 0.354	0.240 Liter Interval 0.194 to 0.287	0.347 Liter Interval 0.282 to 0.412

SECONDARY outcome

Timeframe: Week 24

Population: mITT Population

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=196 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=199 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=205 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=198 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=102 Participants Spiriva Respimat 2.5 μg
Change From Baseline in Morning Pre-dose Trough FEV1	0.142 Liter Interval 0.097 to 0.188	0.108 Liter Interval 0.063 to 0.153	0.142 Liter Interval 0.098 to 0.187	0.129 Liter Interval 0.084 to 0.174	0.150 Liter Interval 0.087 to 0.213

SECONDARY outcome

Timeframe: over 24 Weeks (timepoints of 4, 12 & 20 weeks)

Population: mITT Population

Rate of moderate to severe Asthma exacerbations (A deterioration of asthma requiring a new or increased dose of ICS for at least 3 days) or severe Asthma exacerbation (Use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days OR a hospitalization or ER visit because of asthma)

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=231 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=240 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=240 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=237 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=118 Participants Spiriva Respimat 2.5 μg
Rate of Moderate to Severe Asthma Exacerbations	0.43 Events per year Standard Error 0.078	0.44 Events per year Standard Error 0.080	0.41 Events per year Standard Error 0.076	0.55 Events per year Standard Error 0.092	0.50 Events per year Standard Error 0.123

SECONDARY outcome

Timeframe: Week 24

Population: mITT Population

ACQ-7: The ACQ, comprising 7 questions, is completed in the clinic and requires subjects to recall their experiences during the previous week (7 days) prior to the study visit. The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze); the ACQ-6 is these symptom measurements plus daily rescue medication use as recalled by the subject; and the ACQ 7 is the ACQ 6 plus airway caliber as measured by pre-bronchodilator FEV1 percent predicted. Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled.

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=189 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=189 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=194 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=187 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=93 Participants Spiriva Respimat 2.5 μg
Change From Baseline in ACQ-7 (Asthma Control Questionnaire)	-0.78 Scores on a scale Interval -0.89 to -0.66	-0.73 Scores on a scale Interval -0.84 to -0.62	-0.90 Scores on a scale Interval -1.01 to -0.79	-0.80 Scores on a scale Interval -0.91 to -0.69	-0.90 Scores on a scale Interval -1.06 to -0.74

SECONDARY outcome

Timeframe: Week 24

Population: mITT Population

ACQ-5:The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze). Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled).

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=195 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=198 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=196 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=196 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=98 Participants Spiriva Respimat 2.5 μg
Change From Baseline in ACQ-5 (Asthma Control Questionnaire)	-0.87 Scores on a scale Interval -1.0 to -0.73	-0.80 Scores on a scale Interval -0.93 to -0.67	-1.02 Scores on a scale Interval -1.15 to -0.89	-0.93 Scores on a scale Interval -1.06 to -0.8	-1.03 Scores on a scale Interval -1.22 to -0.85

SECONDARY outcome

Timeframe: Week 24

Population: mITT Population

AQLQ +12 - Asthma Quality of Life Questionnaire The AQLQ +12 is a 32-item validated subject-administered questionnaire that was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (≥18 years of age) and adolescents (12 to 17 years of age) with asthma. The 32 questions in the AQLQ +12 are in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). All 4 domains contain standard specific questions relating to each domain. Subjects are asked to think about how they have been during the previous 2 weeks. Responses to each of the 32 questions are on a 7-point scale (7=no impairment to 1=severe impairment). The overall AQLQ +12 score is the mean of all 32 responses. Overall scores range from 1=severe impairment to 7=no impairment.

Outcome measures

Outcome measures
Measure	GP MDI 28.8 μg n=191 Participants Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=191 Participants Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=191 Participants Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=188 Participants Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=94 Participants Spiriva Respimat 2.5 μg
Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12)	0.89 Scores on a scale Interval 0.74 to 1.04	0.90 Scores on a scale Interval 0.75 to 1.04	1.02 Scores on a scale Interval 0.87 to 1.16	0.96 Scores on a scale Interval 0.82 to 1.11	1.04 Scores on a scale Interval 0.84 to 1.25

Adverse Events

GP MDI 28.8 μg

Serious events: 9 serious events

Other events: 33 other events

Deaths: 0 deaths

GP MDI 14.4 μg

Serious events: 7 serious events

Other events: 35 other events

Deaths: 0 deaths

GP MDI 7.2 μg

Serious events: 6 serious events

Other events: 33 other events

Deaths: 0 deaths

Placebo MDI

Serious events: 7 serious events

Other events: 29 other events

Deaths: 0 deaths

Spiriva Respimat 2.5 μg

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GP MDI 28.8 μg n=235 participants at risk Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=240 participants at risk Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=240 participants at risk Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=237 participants at risk Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=119 participants at risk Spiriva Respimat 2.5 μg
Infections and infestations Urinary tract infection	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Influenza	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.84% 1/119 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Cellulitis	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Pneumonia	0.85% 2/235 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Arthritis infective	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Kindey infection	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Klebsiella bacteraemia	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Metapneumovirus infection	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Pneumonia viral	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Sepsis	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Respiratory, thoracic and mediastinal disorders Asthma	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.83% 2/240 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.84% 1/119 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Injury, poisoning and procedural complications Concussion	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Nervous system disorders Cerbrovascular accident	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
General disorders Adverse drug reaction	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
General disorders Non cardiac chest pain	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Metabolism and nutrition disorders Dehydration	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Renal and urinary disorders Acute kidney injury	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Reproductive system and breast disorders Adnexal torsion	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Hepatobiliary disorders Cholecystitis	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Social circumstances Miscarriage of partner	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Gastrointestinal disorders Abdominal pain	0.43% 1/235 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Renal and urinary disorders Nephrolithiasis	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Injury, poisoning and procedural complications Post traumatic pain	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/240 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.43% 1/235 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/237 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Psychiatric disorders Suicidal ideation	0.00% 0/235 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/240 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.42% 1/237 • Number of events 1 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	0.00% 0/119 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment

Other adverse events

Other adverse events
Measure	GP MDI 28.8 μg n=235 participants at risk Glycopyrronium Metered Dose Inhalation 28.8 μg	GP MDI 14.4 μg n=240 participants at risk Glycopyrronium Metered Dose Inhalation 14.4 μg	GP MDI 7.2 μg n=240 participants at risk Glycopyrronium Metered Dose Inhalation 7.2μg	Placebo MDI n=237 participants at risk Placebo Metered Dose Inhalation	Spiriva Respimat 2.5 μg n=119 participants at risk Spiriva Respimat 2.5 μg
Infections and infestations Upper respiratory tract infection	6.0% 14/235 • Number of events 15 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	5.8% 14/240 • Number of events 14 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	5.8% 14/240 • Number of events 14 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	8.0% 19/237 • Number of events 20 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	5.0% 6/119 • Number of events 7 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Nasopharyngitis	4.7% 11/235 • Number of events 12 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	6.2% 15/240 • Number of events 19 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	7.1% 17/240 • Number of events 19 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	3.4% 8/237 • Number of events 10 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	1.7% 2/119 • Number of events 2 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment
Infections and infestations Sinusitis	4.3% 10/235 • Number of events 10 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	2.9% 7/240 • Number of events 8 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	1.7% 4/240 • Number of events 4 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	1.3% 3/237 • Number of events 3 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment	5.9% 7/119 • Number of events 7 • Serious Adverse events were collected from the time subject signed Informed Consent to the time of the final follow-up telephone call up to approximately 30 weeks. Adverse Events were collected from the time subject was randomized up to approximately 26 weeks. The safety analysis set was defined as data from all subjects who were randomized to treatment and received any amount of the study treatment

Additional Information

Pearl Therapeutics, Inc.

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER