Asthma
Conditions
Brief summary
This is a Phase 3B, 12-week, multicenter, open-label study to evaluate the relationship between albuterol sulfate (ABS) eMDPI and clinical asthma exacerbation (CAE) in adult participants at least 18 years of age with exacerbation-prone asthma. The ABS eMDPI dose will be 90 micrograms (mcg), 1 to 2 inhalations every 4 hours as needed, but participant dosing will not be limited to this dosing regimen. The purpose of this study is to evaluate the relationship between albuterol dosing and CAE.
Interventions
Albuterol sulfate will be administered as per the dose and schedule specified in the arm.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant has had at least 1 episode of a severe CAE over the past 12 months before screening. If on a biologic (for example, omalizumab, mepolizumab, or reslizumab) and/or post-bronchial thermoplasty, exacerbation has occurred after these interventions. * The participant is using a moderate-dose inhaled corticosteroid (ICS) equivalent to at least 440 mcg daily of fluticasone propionate. * The participant's baseline asthma therapy regimen, including oral corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, long-acting beta agonist (LABA), long-acting muscarinic agent, or cromolyn, biologicals, theophylline, or mepolizumab, is allowed. * 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 short-acting beta 2 agonist (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 at least 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 asthma. * The participant has used an investigational drug within 5 half-lives of it being discontinued or 1 month of baseline visit, 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). 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE | Baseline (Day 1) to Week 12 | 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. |
| Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE | Baseline to Week 12 | 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. |
| Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased | Baseline to Week 12 | 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). |
| Number of Albuterol Uses in the 24 Hours Preceding a Severe CAE | Baseline to Week 12 | 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 albuterol inhalations used in the 24 hours preceeding a severe CAE is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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'. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| ABS eMDPI 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. | 397 |
| Total | 397 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Other than specified | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | ABS eMDPI |
|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 14.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 99 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 298 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of Asthma Exacerbations in the Past 12 Months | 1.5 exacerbations STANDARD_DEVIATION 1.29 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 74 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 313 Participants |
| Sex: Female, Male Female | 318 Participants |
| Sex: Female, Male Male | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 397 |
| other Total, other adverse events | 68 / 397 |
| serious Total, serious adverse events | 6 / 397 |
Outcome results
Primary
Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE
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.
Time frame: Baseline (Day 1) to Week 12
Population: ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABS eMDPI | Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE | 17 percentage of participants |
Primary
Number of Albuterol Uses in the 24 Hours Preceding a Severe 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 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 albuterol inhalations used in the 24 hours preceeding a severe CAE is reported.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABS eMDPI | Number of Albuterol Uses in the 24 Hours Preceding a Severe CAE | 5.9 inhalations | Standard Deviation 7.95 |
Primary
Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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
Total Number of Inhalations in the Days Preceding the Peak of a Severe 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 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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
| ABS eMDPI | 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 |
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'.
Time frame: Baseline up to week 12
Population: ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Any AEs | 127 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Severe AEs | 41 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 2 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Treatment-related severe AE | 0 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Serious AEs | 6 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 2 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | CAE related AEs | 73 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Device-related AEs | 3 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | AEs leading to death | 0 Participants |