Trial Outcomes & Findings for Patient Empowered Strategy to Reduce Asthma Morbidity in Highly Impacted Populations; PeRson EmPowered Asthma RElief (NCT NCT02995733)

Last Updated: 2023-01-19

Results Overview

Our primary outcome, the rate of asthma exacerbations per year, is defined as the number of exacerbations, emergency room visits, or hospitalizations requiring oral or parenteral corticosteroids, per patient per year

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1220 participants

Primary outcome timeframe

monthly through study completion an average of 15 months

Results posted on

2023-01-19

Participant Flow

1220 participants were enrolled, however, 19 participants were not followed and were dropped from analysis due to the site closure. They were not included in the primary analyses but were included in safety reporting. Two sites were enrolling simultaneously and there was one additional participant enrolled accidentally.

Participant milestones

Participant milestones
Measure	PARTICS addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care Provider-enhanced usual care arm; no change in asthma management
Overall Study STARTED	609	611
Overall Study COMPLETED	542	557
Overall Study NOT COMPLETED	67	54

Reasons for withdrawal

Reasons for withdrawal
Measure	PARTICS addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care Provider-enhanced usual care arm; no change in asthma management
Overall Study Study site closed	9	10
Overall Study Death	3	4
Overall Study Withdrawal by Subject	6	2
Overall Study Removed by study team due to inappropriate behavior	1	0
Overall Study Lost to Follow-up	48	37
Overall Study Other	0	1

Baseline Characteristics

376 participants answered questions about smoking pack-years. Non-smokers are those who have not smoked within 1 year and have smoked less than 10 pack-years in their lifetime. 143 are current smokers, 100 are former smokers, and 133 are non-smokers with less than 10 pack-years.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PARTICS n=600 Participants addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=601 Participants Provider-enhanced usual care arm; no change in asthma management	Total n=1201 Participants Total of all reporting groups
Age, Continuous	48.3 years STANDARD_DEVIATION 13.5 • n=600 Participants	47.0 years STANDARD_DEVIATION 13.9 • n=601 Participants	47.7 years STANDARD_DEVIATION 13.7 • n=1201 Participants
Sex: Female, Male Female	508 Participants n=600 Participants	497 Participants n=601 Participants	1005 Participants n=1201 Participants
Sex: Female, Male Male	92 Participants n=600 Participants	104 Participants n=601 Participants	196 Participants n=1201 Participants
Race/Ethnicity, Customized Race/ethnicity · African American/Black	303 Participants n=600 Participants	300 Participants n=601 Participants	603 Participants n=1201 Participants
Race/Ethnicity, Customized Race/ethnicity · Hispanic/Latinx	297 Participants n=600 Participants	301 Participants n=601 Participants	598 Participants n=1201 Participants
Region of Enrollment Puerto Rico	51 Participants n=600 Participants	51 Participants n=601 Participants	102 Participants n=1201 Participants
Region of Enrollment United States	549 Participants n=600 Participants	550 Participants n=601 Participants	1099 Participants n=1201 Participants
Body mass index (BMI) (kg/m2)	35.2 kilograms per meters squared STANDARD_DEVIATION 9.1 • n=600 Participants	35.1 kilograms per meters squared STANDARD_DEVIATION 9.5 • n=601 Participants	35.1 kilograms per meters squared STANDARD_DEVIATION 9.3 • n=1201 Participants
Obesity	421 Participants n=600 Participants	403 Participants n=601 Participants	824 Participants n=1201 Participants
Smoking status Current smoker	69 Participants n=600 Participants	74 Participants n=601 Participants	143 Participants n=1201 Participants
Smoking status Former smoker	54 Participants n=600 Participants	46 Participants n=601 Participants	100 Participants n=1201 Participants
Smoking status Non-smoker	477 Participants n=600 Participants	481 Participants n=601 Participants	958 Participants n=1201 Participants
Nonsmoker or former smoker in smoking environment	96 Participants n=600 Participants	107 Participants n=601 Participants	203 Participants n=1201 Participants
Number of pack-years of smoking	12.4 pack-years STANDARD_DEVIATION 13.80 • n=190 Participants • 376 participants answered questions about smoking pack-years. Non-smokers are those who have not smoked within 1 year and have smoked less than 10 pack-years in their lifetime. 143 are current smokers, 100 are former smokers, and 133 are non-smokers with less than 10 pack-years.	15.8 pack-years STANDARD_DEVIATION 19.79 • n=186 Participants • 376 participants answered questions about smoking pack-years. Non-smokers are those who have not smoked within 1 year and have smoked less than 10 pack-years in their lifetime. 143 are current smokers, 100 are former smokers, and 133 are non-smokers with less than 10 pack-years.	14.1 pack-years STANDARD_DEVIATION 17.09 • n=376 Participants • 376 participants answered questions about smoking pack-years. Non-smokers are those who have not smoked within 1 year and have smoked less than 10 pack-years in their lifetime. 143 are current smokers, 100 are former smokers, and 133 are non-smokers with less than 10 pack-years.
Maintenance asthma medications: Inhaled glucocorticoid without long-acting beta-agonist	171 Participants n=600 Participants	169 Participants n=601 Participants	340 Participants n=1201 Participants
Maintenance asthma medications: Combination inhaled glucocorticoid with long-acting beta-agonist	428 Participants n=600 Participants	431 Participants n=601 Participants	859 Participants n=1201 Participants
Maintenance asthma medications: Long-acting muscarinic antagonist	64 Participants n=600 Participants	79 Participants n=601 Participants	143 Participants n=1201 Participants
Maintenance asthma medications: Leukotriene-receptor antagonist	308 Participants n=600 Participants	290 Participants n=601 Participants	598 Participants n=1201 Participants
Maintenance asthma medications: Biologic agent	17 Participants n=600 Participants	19 Participants n=601 Participants	36 Participants n=1201 Participants
Use of quick-reliever nebulizer	408 Participants n=600 Participants	396 Participants n=601 Participants	804 Participants n=1201 Participants
Number of quick-reliever nebulizations per week	2.7 Nebulizations per week STANDARD_DEVIATION 4.6 • n=408 Participants • Only participants who reported using a nebulizer are included in this measure.	3.0 Nebulizations per week STANDARD_DEVIATION 4.8 • n=396 Participants • Only participants who reported using a nebulizer are included in this measure.	2.9 Nebulizations per week STANDARD_DEVIATION 4.7 • n=804 Participants • Only participants who reported using a nebulizer are included in this measure.
Number of coexisting conditions 0	166 Participants n=600 Participants	191 Participants n=601 Participants	357 Participants n=1201 Participants
Number of coexisting conditions 1	150 Participants n=600 Participants	126 Participants n=601 Participants	276 Participants n=1201 Participants
Number of coexisting conditions 2	133 Participants n=600 Participants	119 Participants n=601 Participants	252 Participants n=1201 Participants
Number of coexisting conditions 3	81 Participants n=600 Participants	86 Participants n=601 Participants	167 Participants n=1201 Participants
Number of coexisting conditions 4 or more	70 Participants n=600 Participants	79 Participants n=601 Participants	149 Participants n=1201 Participants
Fractional exhaled nitric oxide (FeNO)	26.7 ppb STANDARD_DEVIATION 27.8 • n=502 Participants • 1003 participants had FeNO data available for analysis.	30.4 ppb STANDARD_DEVIATION 34.9 • n=501 Participants • 1003 participants had FeNO data available for analysis.	28.6 ppb STANDARD_DEVIATION 31.6 • n=1003 Participants • 1003 participants had FeNO data available for analysis.
Fractional exhaled nitric oxide (FeNO), ≥30 ppb	148 Participants n=502 Participants • 1003 participants had FeNO data available for analysis.	154 Participants n=501 Participants • 1003 participants had FeNO data available for analysis.	302 Participants n=1003 Participants • 1003 participants had FeNO data available for analysis.
Absolute eosinophil count	188 cells/μL n=502 Participants • 996 participants had eosinophil count data available for analysis.	195 cells/μL n=494 Participants • 996 participants had eosinophil count data available for analysis.	192 cells/μL n=996 Participants • 996 participants had eosinophil count data available for analysis.
Absolute eosinophil count ≥300 cells/μL	128 Participants n=502 Participants • 996 participants had eosinophil count data available for analysis.	137 Participants n=494 Participants • 996 participants had eosinophil count data available for analysis.	265 Participants n=996 Participants • 996 participants had eosinophil count data available for analysis.
History of ≥1 asthma exacerbation in past year	440 Participants n=600 Participants	427 Participants n=601 Participants	867 Participants n=1201 Participants
Asthma Control Test score	14.7 units on a scale STANDARD_DEVIATION 4.4 • n=600 Participants	14.5 units on a scale STANDARD_DEVIATION 4.5 • n=601 Participants	14.6 units on a scale STANDARD_DEVIATION 4.4 • n=1201 Participants
Asthma Symptom Utility Index score	0.67 units on a scale STANDARD_DEVIATION 0.22 • n=600 Participants • One participant in the Usual Care group is missing baseline ASUI data.	0.67 units on a scale STANDARD_DEVIATION 0.21 • n=600 Participants • One participant in the Usual Care group is missing baseline ASUI data.	0.67 units on a scale STANDARD_DEVIATION 0.21 • n=1200 Participants • One participant in the Usual Care group is missing baseline ASUI data.
Medication Adherence Report Scale-5 score	4.2 units on a scale STANDARD_DEVIATION 0.8 • n=600 Participants	4.2 units on a scale STANDARD_DEVIATION 0.8 • n=601 Participants	4.2 units on a scale STANDARD_DEVIATION 0.8 • n=1201 Participants
Low or marginal health literacy	101 Participants n=599 Participants • One participant in the PARTICS group is missing baseline data measuring health literacy.	100 Participants n=601 Participants • One participant in the PARTICS group is missing baseline data measuring health literacy.	201 Participants n=1200 Participants • One participant in the PARTICS group is missing baseline data measuring health literacy.
Participant-perceived overall health Excellent	13 Participants n=600 Participants	9 Participants n=601 Participants	22 Participants n=1201 Participants
Participant-perceived overall health Very good	68 Participants n=600 Participants	60 Participants n=601 Participants	128 Participants n=1201 Participants
Participant-perceived overall health Good	200 Participants n=600 Participants	194 Participants n=601 Participants	394 Participants n=1201 Participants
Participant-perceived overall health Fair	257 Participants n=600 Participants	272 Participants n=601 Participants	529 Participants n=1201 Participants
Participant-perceived overall health Poor	62 Participants n=600 Participants	66 Participants n=601 Participants	128 Participants n=1201 Participants

PRIMARY outcome

Timeframe: monthly through study completion an average of 15 months

Outcome measures

Outcome measures
Measure	PARTICS n=600 Participants addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=601 Participants Provider-enhanced usual care arm; no change in asthma management
Rate of Asthma Exacerbations Per Year	0.69 Adjusted annualized exacerbations Interval 0.61 to 0.78	0.82 Adjusted annualized exacerbations Interval 0.73 to 0.92

SECONDARY outcome

Timeframe: Monthly through study completion an average of 15 months

Asthma control represents the degree to which impairment (impact of asthma on patient's daily life) is minimized and the goals of therapy are met. The Asthma Control Test is a participant-administered tool for assessing the level of asthma control. Total scores range from 5 to 25, with a score of 20 to 25 indicating well-controlled asthma, a score of 16 to 19 indicating asthma that was not well controlled, and a score of 5 to 15 indicating very poorly controlled asthma. The minimal clinically important difference is 3 points

Outcome measures

Outcome measures
Measure	PARTICS n=600 Participants addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=601 Participants Provider-enhanced usual care arm; no change in asthma management
Asthma Control: Asthma Control Test (ACT) Score, Least-squares Mean Change From Baseline	3.4 units on a scale Interval 3.1 to 3.6	2.5 units on a scale Interval 2.3 to 2.8

SECONDARY outcome

Timeframe: Monthly through study completion an average of 15 months

The ideal outcome measure for any comparative effectiveness analysis captures the risks and benefits for each of the interventions from the patient's point of view. The use of a preference-based instrument, the Asthma Symptom Utility Index (ASUI), captures this important information. The Asthma Symptom Utility Index is a participant-administered tool for assessing preference-based quality of life. Scores range from 0 (worst possible symptoms) to 1 (no symptoms). The minimal clinically important difference is 0.09.

Outcome measures

Outcome measures
Measure	PARTICS n=600 Participants addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=601 Participants Provider-enhanced usual care arm; no change in asthma management
Preference Based Quality of Life: Asthma Symptom Utility Index (ASUI), Least-squares Mean Change From Baseline	0.12 units on a scale Interval 0.11 to 0.13	0.08 units on a scale Interval 0.07 to 0.09

SECONDARY outcome

Timeframe: Monthly through study completion an average of 15 months

Defined as days not able to work or go to school because of asthma symptoms OR days not able to carry out usual activities due to asthma

Outcome measures

Outcome measures
Measure	PARTICS n=600 Participants addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=601 Participants Provider-enhanced usual care arm; no change in asthma management
Days Per Year Lost From Work or School/ Days Unable to Carry Out Usual Activities Due to Asthma	13.4 days per year Interval 11.9 to 15.2	16.8 days per year Interval 14.9 to 18.9

Adverse Events

PARTICS

Serious events: 75 serious events

Other events: 0 other events

Deaths: 3 deaths

Usual Care

Serious events: 74 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Elliot Israel

Brigham and Women's Hospital

Phone: 617-732-8110

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	PARTICS n=609 participants at risk addition of PARTICS strategy - Patient Activated Reliever-Triggered Inhaled CorticoSteroid (PARTICS) using QVAR . Patient will use inhaled corticosteroid at time of rescue inhaler use PARTICS using QVAR: Patient takes inhaled corticosteroid at the time of rescue inhaler use	Usual Care n=611 participants at risk Provider-enhanced usual care arm; no change in asthma management
Respiratory, thoracic and mediastinal disorders Asthma	7.1% 43/609 • Number of events 68 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	7.4% 45/611 • Number of events 85 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Cardiac disorders Cardiac events	1.3% 8/609 • Number of events 9 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	1.6% 10/611 • Number of events 10 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Gastrointestinal disorders Gastrointestinal disorders	0.99% 6/609 • Number of events 6 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.65% 4/611 • Number of events 4 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Blood and lymphatic system disorders Hematology/oncology	0.00% 0/609 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.65% 4/611 • Number of events 11 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Immune system disorders Immune system disorders	0.16% 1/609 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.33% 2/611 • Number of events 2 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Infections and infestations Infections and infestations	2.0% 12/609 • Number of events 12 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	1.3% 8/611 • Number of events 9 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Metabolism and nutrition disorders	0.16% 1/609 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.00% 0/611 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorders	0.33% 2/609 • Number of events 2 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.82% 5/611 • Number of events 5 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Nervous system disorders Nervous system disorders	0.49% 3/609 • Number of events 4 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.00% 0/611 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Psychiatric disorders Psychiatric disorders	0.00% 0/609 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.33% 2/611 • Number of events 6 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Renal and urinary disorders Renal/urinary disorders	0.33% 2/609 • Number of events 2 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.16% 1/611 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Reproductive system and breast disorders Reproductive system and breast disorders	0.16% 1/609 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.00% 0/611 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic, mediastinal disorders	0.99% 6/609 • Number of events 7 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.98% 6/611 • Number of events 6 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	0.00% 0/609 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.16% 1/611 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Psychiatric disorders Substance abuse	0.00% 0/609 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.16% 1/611 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
Vascular disorders Vascular disorders	0.33% 2/609 • Number of events 2 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	0.16% 1/611 • Number of events 1 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.
General disorders Unclassified elsewhere	1.6% 10/609 • Number of events 11 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.	1.5% 9/611 • Number of events 11 • From enrollment to study completion, an average of 15 months per participant. SAE was defined as any event that resulted in death, hospitalization, persistent/significant disability, or congenital anomaly/birth defect; or was otherwise life-threatening. Data on adverse events that resulted in hospitalization or death were obtained by participant report or site report. Adverse events were not monitored/assessed with regard to the specific Adverse Event Term.