Evaluate the Relationship Between Use of Albuterol Multid... | NCT03256695

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
ABS eMDPI	Experimental	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)

Name	Type	Description	Arm Group Labels	Other Names
Albuterol sulfate (ABS)	Drug	ABS will be administered via eMDPI as per the dose and schedule specified in the arm.	ABS eMDPI

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Clinical Exacerbation of COPD (CE-COPD) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CE-COPD	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.	Baseline (Day 1) to Week 12
Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event	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.	Baseline to Week 12
Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased	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.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	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 Module

Eligibility Criteria

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.

Name	Affiliation	Role
Teva Medical Expert, MD	Teva Branded Pharmaceutical Products R&D, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 14682		Andalusia	Alabama	36420	United States
Teva Investigational Site 14704

PubMed Identifier	Type	Citation	Retractions
40355297	Derived	Snyder LD, DePietro M, Reich M, Neely ML, Lugogo N, Pleasants R, Li T, Granovsky L, Brown R, Safioti G. Predictive machine learning algorithm for COPD exacerbations using a digital inhaler with integrated sensors. BMJ Open Respir Res. 2025 May 12;12(1):e002577. doi: 10.1136/bmjresp-2024-002577.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	ABS eMDPI	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 26, 2017	Jun 4, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Clinical Exacerbation of COPD (CE-COPD) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CE-COPD

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.

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.

Posted

Number

percentage of participants

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	ABS eMDPI	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.

Units	Counts
Participants	OG000396

Title

Denominators

Categories

Title	Measurements
	OG00028

Primary

Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event

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.

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.

Posted

Mean

Standard Deviation

inhalations

Baseline to Week 12

ID	Title	Description
OG000	ABS eMDPI	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.

Primary

Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased

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.

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.

Posted

Mean

Standard Deviation

days

Baseline to Week 12

ID	Title	Description
OG000	ABS eMDPI	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.

Primary

Number of Albuterol Uses in the 24 Hours Preceding a CE-COPD

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.

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.

Posted

Mean

Standard Deviation

inhalations/24 hours

Baseline to Week 12

ID	Title	Description
OG000	ABS eMDPI	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.

Secondary

Number of Participants With Adverse Events (AEs)

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'.

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

Posted

Count of Participants

Participants

Baseline up to Week 12

ID	Title	Description
OG000	ABS eMDPI	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute left ventricular failure	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Angina pectoris	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Bradycardia	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Cardiac arrest	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Cardiomyopathy	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Left ventricular failure	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Myocardial infarction	Cardiac disorders	MedDRA v20.0	Systematic Assessment	EG0002 events2 affected405 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Chest pain	General disorders	MedDRA v20.0	Systematic Assessment	EG0002 events2 affected405 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Diverticulitis	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Influenza	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0002 events2 affected405 at risk
Osteomyelitis acute	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Pneumonia	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0005 events5 affected405 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Pneumonia viral	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Rhinovirus infection	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Sepsis	Infections and infestations	MedDRA v20.0	Systematic Assessment	EG0002 events2 affected405 at risk
Burns first degree	Injury, poisoning and procedural complications	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Influenza A virus test positive	Investigations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Influenza B virus test positive	Investigations	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Syncope	Nervous system disorders	MedDRA v20.0	Systematic Assessment	EG0002 events2 affected405 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Substance use disorder	Psychiatric disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA v20.0	Systematic Assessment	EG0006 events5 affected405 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA v20.0	Systematic Assessment	EG00024 events22 affected405 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v20.0	Systematic Assessment	EG0001 events1 affected405 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines