Chronic Obstructive Pulmonary Disease
Conditions
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.
Interventions
DRUGAlbuterol sulfate (ABS)
ABS will be administered via eMDPI 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
40 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| 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 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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 405 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Non-compliance with study drug | 1 |
| Overall Study | Other than specified | 3 |
| Overall Study | Protocol Violation | 5 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | ABS eMDPI |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 371 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of COPD Exacerbations in the Past 12 Months | 1.5 exacerbations STANDARD_DEVIATION 0.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 365 Participants |
| Sex: Female, Male Female | 220 Participants |
| Sex: Female, Male Male | 185 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 405 |
| other Total, other adverse events | 94 / 405 |
| serious Total, serious adverse events | 44 / 405 |
Outcome results
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.
Time frame: Baseline (Day 1) to Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| ABS eMDPI | Clinical Exacerbation of COPD (CE-COPD) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CE-COPD | 28 percentage of participants |
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.
Time frame: Baseline to Week 12
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABS eMDPI | Number of Albuterol Uses in the 24 Hours Preceding a CE-COPD | 3.7 inhalations/24 hours | Standard Deviation 4.36 |
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.
Time frame: Baseline to Week 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABS eMDPI | Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased | Days from albuterol use >20% increase to CE-COPD | 32.7 days | Standard Deviation 19.92 |
| ABS eMDPI | Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased | Days from 2 inhalations increase to CE-COPD | 31.2 days | Standard Deviation 21.3 |
| ABS eMDPI | Number of Days Prior to the Symptom Peak of a CE-COPD Event When Albuterol Use Increased | Days from 4 inhalations increase to CE-COPD | 30.4 days | Standard Deviation 21.24 |
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.
Time frame: Baseline to Week 12
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 1 prior to CE-COPD symptom peak | 3.7 inhalations | Standard Deviation 4.36 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 3 prior to CE-COPD symptom peak | 3.5 inhalations | Standard Deviation 4.61 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 5 prior to CE-COPD symptom peak | 4.2 inhalations | Standard Deviation 5.35 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 7 prior to CE-COPD symptom peak | 3.4 inhalations | Standard Deviation 4.45 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 10 prior to CE-COPD symptom peak | 3.2 inhalations | Standard Deviation 4.41 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 14 prior to CE-COPD symptom peak | 3.4 inhalations | Standard Deviation 4.42 |
| ABS eMDPI | Total Number of Albuterol Inhalations in the Days Preceding the Symptom Peak of a CE-COPD Event | Day 21 prior to CE-COPD symptom peak | 3.1 inhalations | Standard Deviation 4.54 |
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 | 190 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Severe AEs | 43 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 | 44 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 8 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | CE-COPD related AEs | 118 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | Device-related AEs | 0 Participants |
| ABS eMDPI | Number of Participants With Adverse Events (AEs) | AEs leading to death | 2 Participants |