Trial Outcomes & Findings for A Study to Evaluate the Relationship Between Use of Albuterol Multidose Dry Powder Inhaler With an eModule (eMDPI) and Exacerbations in Participants With Asthma (NCT NCT02969408)

Last Updated: 2021-11-09

Results Overview

CAE was an occurrence of either severe CAE or moderate CAE. Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 milligrams (mg) prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Moderate CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days, or an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization associated with an increase in asthma therapy that did not qualify for severe CAE as defined above.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

397 participants

Primary outcome timeframe

Baseline (Day 1) to Week 12

Results posted on

2021-11-09

Participant Flow

A total of 449 participants with exacerbation-prone asthma were screened, of which 397 participants at 45 investigational centers in the US met entry criteria and were considered to be eligible for enrollment into the study.

Participant milestones

Participant milestones
Measure	ABS eMDPI Participants received 90 micrograms (mcg) of albuterol sulfate (ABS) via a multidose dry powder inhaler (MDPI) with an eModule (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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Overall Study STARTED	397
Overall Study Used ABS eMDPI at Least Once	370
Overall Study COMPLETED	381
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	ABS eMDPI Participants received 90 micrograms (mcg) of albuterol sulfate (ABS) via a multidose dry powder inhaler (MDPI) with an eModule (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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	8
Overall Study Lost to Follow-up	4
Overall Study Protocol Violation	1
Overall Study Other than specified	1

Baseline Characteristics

Here, 'number analyzed' signifies number of participants with asthma exacerbations.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABS eMDPI n=397 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Age, Continuous	50.1 years STANDARD_DEVIATION 14.93 • n=397 Participants
Sex: Female, Male Female	318 Participants n=397 Participants
Sex: Female, Male Male	79 Participants n=397 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	99 Participants n=397 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	298 Participants n=397 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=397 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=397 Participants
Race/Ethnicity, Customized Asian	3 Participants n=397 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=397 Participants
Race/Ethnicity, Customized Black or African American	74 Participants n=397 Participants
Race/Ethnicity, Customized White	313 Participants n=397 Participants
Race/Ethnicity, Customized Other	2 Participants n=397 Participants
Number of Asthma Exacerbations in the Past 12 Months	1.5 exacerbations STANDARD_DEVIATION 1.29 • n=394 Participants • Here, 'number analyzed' signifies number of participants with asthma exacerbations.

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

Outcome measures

Outcome measures
Measure	ABS eMDPI n=397 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE	17 percentage of participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed' signifies number of participants experiencing at least 1 severe CAE. Here, 'number analyzed' signifies participants who reported albuterol use in specified time interval.

Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Total number of inhalations taken in 1 day (that is, the 24-hour period on the day prior to the date of the CAE symptom peak) and at 3, 5, 7, 10, 14, and 21 days preceding the date of the severe CAE symptom peak were reported.

Outcome measures

Outcome measures
Measure	ABS eMDPI n=37 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 10 prior to CAE	4.5 inhalations Standard Deviation 4.24
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 21 prior to CAE	4.0 inhalations Standard Deviation 3.06
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 1 prior to CAE	5.9 inhalations Standard Deviation 7.95
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 3 prior to CAE	6.1 inhalations Standard Deviation 9.93
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 5 prior to CAE	3.6 inhalations Standard Deviation 2.89
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 7 prior to CAE	4.0 inhalations Standard Deviation 2.61
Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE Day 14 prior to CAE	3.2 inhalations Standard Deviation 1.87

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed'= number of participants experiencing at least 1 severe CAE. 'Number analyzed'= participants who had any single day prior to CAE where their albuterol use exceeded 4, 12, or 20 inhalations in that day.

Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Number of days prior to the peak of a severe CAE when albuterol use first increased to greater than (\>) 4, \>12, and \>20 inhalations was reported. Participants were counted in more than 1 category (that is, all of the \>20 inhalation participants were also counted in the \>12 category, and in the \>4 category).

Outcome measures

Outcome measures
Measure	ABS eMDPI n=37 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased Albuterol use >4 inhalations	39.3 days Standard Deviation 26.79
Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased Albuterol use >12 inhalations	40.3 days Standard Deviation 26.95
Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased Albuterol use >20 inhalations	34.0 days Standard Deviation 30.84

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed' signifies number of participants who experienced at least 1 severe CAE and reported albuterol use in the 24 hours preceding a severe CAE.

Outcome measures

Outcome measures
Measure	ABS eMDPI n=31 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Number of Albuterol Uses in the 24 Hours Preceding a Severe CAE	5.9 inhalations Standard Deviation 7.95

SECONDARY outcome

Timeframe: Baseline up to week 12

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

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'.

Outcome measures

Outcome measures
Measure	ABS eMDPI n=397 Participants Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Number of Participants With Adverse Events (AEs) Serious AEs	6 Participants
Number of Participants With Adverse Events (AEs) Any AEs	127 Participants
Number of Participants With Adverse Events (AEs) Severe AEs	41 Participants
Number of Participants With Adverse Events (AEs) Treatment-related AEs	2 Participants
Number of Participants With Adverse Events (AEs) Treatment-related severe AE	0 Participants
Number of Participants With Adverse Events (AEs) AEs leading to discontinuation from study	2 Participants
Number of Participants With Adverse Events (AEs) CAE related AEs	73 Participants
Number of Participants With Adverse Events (AEs) Device-related AEs	3 Participants
Number of Participants With Adverse Events (AEs) AEs leading to death	0 Participants

Adverse Events

ABS eMDPI

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ABS eMDPI n=397 participants at risk Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Cardiac disorders Acute myocardial infarction	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Cardiac disorders Myocardial infarction	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Infections and infestations Gastroenteritis salmonella	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Infections and infestations Pneumonia	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Facial bones fracture	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Fractured sacrum	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Humerus fracture	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Ilium fracture	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Pubis fracture	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Rib fracture	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Injury, poisoning and procedural complications Road traffic accident	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Metabolism and nutrition disorders Dehydration	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Metabolism and nutrition disorders Hypokalaemia	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Nervous system disorders Migraine	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.25% 1/397 • Number of events 2 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Respiratory, thoracic and mediastinal disorders Asthma	0.50% 2/397 • Number of events 2 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
Vascular disorders Deep vein thrombosis	0.25% 1/397 • Number of events 1 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.

Other adverse events

Other adverse events
Measure	ABS eMDPI n=397 participants at risk Participants received 90 mcg of 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 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 asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician.
Respiratory, thoracic and mediastinal disorders Asthma	17.1% 68/397 • Number of events 81 • Baseline up to Week 12 ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER