Evaluate the Relationship Between Use of Albuterol Multidose Dry Powder Inhaler With an eModule (eMDPI) and Exacerbations in Participants With Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03256695
• Collaborator: (none)
• Enrollment: 405
• Locations: 40
• Arm: 1
• Actual Duration (Months): 6.6
• Patients Per Site: 10.1
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This is a Phase 3B, 12-week, multicenter, open-label study to evaluate the relationship between as-needed usage of albuterol eMDPI and Clinical Exacerbation-Chronic Obstructive Pulmonary Disease (CE-COPD) in adult participants at least 40 years of age with exacerbation-prone COPD.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Albuterol sulfate (ABS)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 405 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12-Week, Open-Label Study to Evaluate the Relationship Between Use of Albuterol eMDPI, an Inhaled Short-Acting Beta Agonist "Rescue" Agent With an eModule, and Exacerbations in Patients (40 Years of Age or Older) With Chronic Obstructive Pulmonary Disease
• Actual Study Start Date: Sep 28, 2017
• Actual Primary Completion Date: Apr 17, 2018
• Actual Study Completion Date: Apr 17, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ABS eMDPI Participants will receive 90 micrograms (mcg) of albuterol sulfate (ABS) via eMDPI (sitting on the upper part of the device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI is a rescue/reliever agent that includes an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants will be allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.

Drug: Albuterol sulfate (ABS); ABS will be administered via eMDPI as per the dose and schedule specified in the arm.

Outcome Measures

Primary Outcome Measures

1. Clinical Exacerbation of COPD (CE-COPD) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CE-COPD [Baseline (Day 1) to Week 12]

   CE-COPD was an occurrence of either severe CE-COPD or moderate CE-COPD. Severe CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with systemic corticosteroids (SCS; at least 10 milligrams [mg] prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization for CE COPD. Moderate CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit) for a CE-COPD, but not a hospitalization.

2. Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event [Baseline to Week 12]

   Severe CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization. Moderate CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, office visit, urgent care visit, or emergency care visit), but not a hospitalization. Total number of inhalations taken in 1 day(24-hour period on day prior to date of CE-COPD symptom peak) and at 3,5,7,10,14, and 21 days preceding the date of CE-COPD symptom peak were reported. If a participant experienced multiple CE-COPD events, number of inhalations preceding symptom peak of a subsequent event was counted since end of previous event. Average of inhalations of all events were presented.

3. Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased [Baseline to Week 12]

   CE-COPD: occurrence of moderate or severe CE-COPD. Severe CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization. Moderate CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit), but not a hospitalization. Number of days of increased albuterol use prior to the symptom peak of a CE-COPD was reported for first increase of daily albuterol use; 2 and 4 inhalations in a single day from baseline. increased daily albuterol use was defined as single-day increase of greater than (>) 20 percent (%) from baseline.

4. Number of Albuterol Uses in the 24 Hours Preceding a CE-COPD [Baseline to Week 12]

   CE-COPD referred to occurrence of moderate or severe CE-COPD. Severe CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization for CE COPD. Moderate CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit) for a CE-COPD, but not a hospitalization. Number of albuterol inhalations used in the 24 hours preceding a moderate or severe CE-COPD was reported.

Secondary Outcome Measures

1. Number of Participants With Adverse Events (AEs) [Baseline up to Week 12]

   AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by investigator. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant has had at least 1 episode of moderate or severe CE-COPD over the past 12 months before screening.

• The participant must be able to demonstrate appropriate use of albuterol from the ABS eMDPI.

• The participant is currently using a short-acting beta agonist (SABA) reliever plus at least one of the following: long-acting beta agonist (LABA), an inhaled corticosteroid (ICS)/LABA, a long-acting muscarinic antagonist (LAMA), or a LABA/LAMA.

• The participant must be willing and able to comply with study requirements as specified in the protocol, including the use of a wearable accelerometer for the subset of participants who consent to use of the device.

• The participant is willing to discontinue all other rescue or maintenance SABA or antimuscarinic agents and replace them with the study-provided ABS eMDPI for the duration of the trial.

• Women of childbearing potential (not surgically sterile or greater than or equal to [≥]2 years postmenopausal) must have exclusively same-sex partners or use a highly effective method of birth control and must agree to continue the use of this method for the duration of the study and for 30 days after discontinuation of the investigational medicinal product (IMP).

• Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

• The participant has any clinically significant medical condition (treated or untreated) that, in the opinion of the investigator, would interfere with participation in the study.

• The participant has any other confounding underlying lung disorder other than COPD.

• The participant has used an investigational drug within 5 half-lives of it being discontinued or within1 month of Visit 2 (Baseline [Day 1]), whichever is longer.

• The participant is a pregnant or lactating woman, or plans to become pregnant during the study. Note: Any woman becoming pregnant during the study will be withdrawn from the study.

• The participant is known to be allergic to albuterol or any of the excipients in the IMP or rescue medication formulation (that is, lactose [milk protein]). Dietary lactose intolerance does not exclude the participant from inclusion in the study or as per the investigator's medical discretion.

• The participant has a history or presence of "silent" infections, including positive testing for human immunodeficiency virus types 1 and 2, hepatitis B, hepatitis C, and tuberculosis.

• Additional criteria apply, please contact the investigator for more information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 14682	Andalusia	Alabama	United States	36420
2	Teva Investigational Site 14704	Anniston	Alabama	United States	36207
3	Teva Investigational Site 14712	Mobile	Alabama	United States	36608
4	Teva Investigational Site 14702	Peoria	Arizona	United States	85381
5	Teva Investigational Site 14706	Gold River	California	United States	95670
6	Teva Investigational Site 14720	Waterbury	Connecticut	United States	06708
7	Teva Investigational Site 14725	Brandon	Florida	United States	33511
8	Teva Investigational Site 14711	Daytona Beach	Florida	United States	32117
9	Teva Investigational Site 14699	DeLand	Florida	United States	32720
10	Teva Investigational Site 14694	Edgewater	Florida	United States	32132
11	Teva Investigational Site 14701	Miami	Florida	United States	33126
12	Teva Investigational Site 14689	Miami	Florida	United States	33135
13	Teva Investigational Site 14678	Miami	Florida	United States	33155
14	Teva Investigational Site 14688	Orlando	Florida	United States	32825
15	Teva Investigational Site 14679	Valparaiso	Indiana	United States	46383
16	Teva Investigational Site 14677	North Dartmouth	Massachusetts	United States	02747
17	Teva Investigational Site 14705	Chesterfield	Missouri	United States	63017
18	Teva Investigational Site 14717	Omaha	Nebraska	United States	68114
19	Teva Investigational Site 14684	Toms River	New Jersey	United States	08755
20	Teva Investigational Site 14710	Charlotte	North Carolina	United States	28207
21	Teva Investigational Site 14696	Gastonia	North Carolina	United States	28054
22	Teva Investigational Site 14722	Greensboro	North Carolina	United States	27408
23	Teva Investigational Site 14692	Winston-Salem	North Carolina	United States	27103
24	Teva Investigational Site 14708	Columbus	Ohio	United States	43215
25	Teva Investigational Site 14703	Dayton	Ohio	United States	45458
26	Teva Investigational Site 14680	Grove City	Ohio	United States	43123
27	Teva Investigational Site 14709	Toledo	Ohio	United States	43617
28	Teva Investigational Site 14724	Willoughby	Ohio	United States	44094
29	Teva Investigational Site 14683	Pittsburgh	Pennsylvania	United States	15243
30	Teva Investigational Site 14681	Charleston	South Carolina	United States	29406
31	Teva Investigational Site 14686	Easley	South Carolina	United States	29640
32	Teva Investigational Site 14719	Gaffney	South Carolina	United States	29341
33	Teva Investigational Site 14691	Greenville	South Carolina	United States	29615
34	Teva Investigational Site 14695	Mount Pleasant	South Carolina	United States	29464
35	Teva Investigational Site 14715	Spartanburg	South Carolina	United States	29303
36	Teva Investigational Site 14718	Spartanburg	South Carolina	United States	29303
37	Teva Investigational Site 14707	Union	South Carolina	United States	29379
38	Teva Investigational Site 14716	San Antonio	Texas	United States	78229
39	Teva Investigational Site 14713	Richmond	Virginia	United States	23225
40	Teva Investigational Site 14687	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

• Study Protocol - Jun 26, 2017
• Statistical Analysis Plan - Apr 27, 2018

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT03256695
• Other Study ID Numbers: ABS-COPD-30065
• First Posted: Aug 22, 2017
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Albuterol

Study Results

Participant Flow

Pre-assignment Detail	A total of 423 participants with exacerbation-prone chronic obstructive pulmonary disease (COPD) were screened, of which 405 participants at 40 investigational centers in the United States met entry criteria and were considered to be eligible for enrollment into the study.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 micrograms (mcg) of albuterol sulfate (ABS) via a multidose dry powder inhaler (MDPI) with an eModule (eMDPI) (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Period Title: Overall Study
STARTED	405
Used ABS eMDPI at Least Once	390
COMPLETED	366
NOT COMPLETED	39

Baseline Characteristics

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Overall Participants	405
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (8.70)
Sex: Female, Male (Count of Participants)
Female	220 54.3%
Male	185 45.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 8.4%
Not Hispanic or Latino	371 91.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 0.2%
Black or African American	38 9.4%
White	365 90.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Number of COPD Exacerbations in the Past 12 Months (exacerbations) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [exacerbations]	1.5 (0.98)

Outcome Measures

1. Primary Outcome

Title	Clinical Exacerbation of COPD (CE-COPD) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CE-COPD
Description	CE-COPD was an occurrence of either severe CE-COPD or moderate CE-COPD. Severe CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with systemic corticosteroids (SCS; at least 10 milligrams [mg] prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization for CE COPD. Moderate CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit) for a CE-COPD, but not a hospitalization.
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Participants with CE-COPD during study Day 1 through study Day 7 were excluded from the analysis.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Measure Participants	396
Number [percentage of participants]	28 6.9%

2. Primary Outcome

Title	Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event
Description	Severe CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization. Moderate CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, office visit, urgent care visit, or emergency care visit), but not a hospitalization. Total number of inhalations taken in 1 day(24-hour period on day prior to date of CE-COPD symptom peak) and at 3,5,7,10,14, and 21 days preceding the date of CE-COPD symptom peak were reported. If a participant experienced multiple CE-COPD events, number of inhalations preceding symptom peak of a subsequent event was counted since end of previous event. Average of inhalations of all events were presented.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set:all enrolled participants regardless of whether a participant took any IMP. Participants with CE-COPD during Day 1 to Day 7 were excluded. 'Overall number of participants analyzed'= participants experiencing at least 1 moderate or severe CE-COPD.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Measure Participants	109
Day 1 prior to CE-COPD symptom peak	3.7 (4.36)
Day 3 prior to CE-COPD symptom peak	3.5 (4.61)
Day 5 prior to CE-COPD symptom peak	4.2 (5.35)
Day 7 prior to CE-COPD symptom peak	3.4 (4.45)
Day 10 prior to CE-COPD symptom peak	3.2 (4.41)
Day 14 prior to CE-COPD symptom peak	3.4 (4.42)
Day 21 prior to CE-COPD symptom peak	3.1 (4.54)

3. Primary Outcome

Title	Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased
Description	CE-COPD: occurrence of moderate or severe CE-COPD. Severe CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization. Moderate CE-COPD: an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit), but not a hospitalization. Number of days of increased albuterol use prior to the symptom peak of a CE-COPD was reported for first increase of daily albuterol use; 2 and 4 inhalations in a single day from baseline. increased daily albuterol use was defined as single-day increase of greater than (>) 20 percent (%) from baseline.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set: all enrolled participants regardless of whether a participant took any IMP. 'Overall number of participants analyzed'= participants experiencing at least 1 moderate or severe CE-COPD. 'Number analyzed'=participants evaluable for specified categories. Participants with CE-COPD during Day 1 to Day 7 were excluded.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Measure Participants	109
Days from albuterol use >20% increase to CE-COPD	32.7 (19.92)
Days from 2 inhalations increase to CE-COPD	31.2 (21.30)
Days from 4 inhalations increase to CE-COPD	30.4 (21.24)

4. Primary Outcome

Title	Number of Albuterol Uses in the 24 Hours Preceding a CE-COPD
Description	CE-COPD referred to occurrence of moderate or severe CE-COPD. Severe CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline) and/or systemic antibiotics and a hospitalization for CE COPD. Moderate CE-COPD was defined as an event that involved worsening respiratory symptoms for at least 2 consecutive days requiring treatment with SCS (at least 10 mg prednisone equivalent above baseline), and/or systemic antibiotics, and an unscheduled encounter (such as a phone call, an office visit, an urgent care visit, or an emergency care visit) for a CE-COPD, but not a hospitalization. Number of albuterol inhalations used in the 24 hours preceding a moderate or severe CE-COPD was reported.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set: all enrolled participants regardless of whether a participant took any IMP. Participants with CE-COPD during Day 1 to Day 7 were excluded. 'Overall number of participants analyzed' = participants who experienced at least 1 moderate or severe CE-COPD and reported albuterol use in the 24 hours preceding a moderate or severe CE-COPD.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Measure Participants	109
Mean (Standard Deviation) [inhalations/24 hours]	3.7 (4.36)

5. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by investigator. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.

Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
Measure Participants	405
Any AEs	190 46.9%
Severe AEs	43 10.6%
Treatment-related AEs	2 0.5%
Treatment-related severe AE	0 0%
Serious AEs	44 10.9%
AEs leading to discontinuation from study	8 2%
CE-COPD related AEs	118 29.1%
Device-related AEs	0 0%
AEs leading to death	2 0.5%

Adverse Events

Time Frame	AEs were collected from signature of the informed consent form (ICF) to Week 12.
Adverse Event Reporting Description	AEs were reported from Baseline (Day 1) up to Week 12. ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Arm/Group Title	ABS eMDPI
Arm/Group Description	Participants received 90 mcg of ABS via eMDPI (that had a sensor on the top of device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other COPD and non-COPD medications as advised by their physician without changes unless deemed necessary by their physician.
All Cause Mortality
	ABS eMDPI
	Affected / at Risk (%)	# Events
Total	2/405 (0.5%)
Serious Adverse Events
	ABS eMDPI
	Affected / at Risk (%)	# Events
Total	44/405 (10.9%)
Cardiac disorders
Acute left ventricular failure	1/405 (0.2%)	1
Acute myocardial infarction	1/405 (0.2%)	1
Angina pectoris	1/405 (0.2%)	1
Atrial fibrillation	1/405 (0.2%)	1
Bradycardia	1/405 (0.2%)	1
Cardiac arrest	1/405 (0.2%)	1
Cardiac failure congestive	1/405 (0.2%)	1
Cardiomyopathy	1/405 (0.2%)	1
Left ventricular failure	1/405 (0.2%)	1
Myocardial infarction	2/405 (0.5%)	2
Gastrointestinal disorders
Diarrhoea	1/405 (0.2%)	1
General disorders
Chest pain	2/405 (0.5%)	2
Hepatobiliary disorders
Cholelithiasis	1/405 (0.2%)	1
Infections and infestations
Diverticulitis	1/405 (0.2%)	1
Influenza	2/405 (0.5%)	2
Osteomyelitis acute	1/405 (0.2%)	1
Pneumonia	5/405 (1.2%)	5
Pneumonia staphylococcal	1/405 (0.2%)	1
Pneumonia viral	1/405 (0.2%)	1
Rhinovirus infection	1/405 (0.2%)	1
Sepsis	2/405 (0.5%)	2
Injury, poisoning and procedural complications
Burns first degree	1/405 (0.2%)	1
Investigations
Influenza A virus test positive	1/405 (0.2%)	1
Influenza B virus test positive	1/405 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	1/405 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/405 (0.2%)	1
Nervous system disorders
Metabolic encephalopathy	1/405 (0.2%)	1
Syncope	2/405 (0.5%)	2
Transient ischaemic attack	1/405 (0.2%)	1
Psychiatric disorders
Substance use disorder	1/405 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	5/405 (1.2%)	6
Chronic obstructive pulmonary disease	22/405 (5.4%)	24
Dyspnoea	1/405 (0.2%)	1
Other (Not Including Serious) Adverse Events
	ABS eMDPI
	Affected / at Risk (%)	# Events
Total	94/405 (23.2%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	94/405 (23.2%)	104

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.