Asthma
Conditions
Keywords
asthma, dry powder inhaler, short-acting beta2-agonist, SABA, bronchoconstriction, bronchodilation, bronchodilator, metered dose inhaler
Brief summary
This is a one-year study to look at the safety of a dry powder inhaler with albuterol. After a one-week run in, for the first 3 months subjects will use an inhaler with either albuterol or a dummy drug at regular times four times a day. Then for the last nine months of the study, all subjects will be given the albuterol dry powder inhaler and will use it only when needed to help with breathing problems. Subjects will need to keep a daily diary (both paper and electronic) throughout the study recording any inhaler use and health problems. There will be visits to the study doctor about once a month for a year. This study is intended to show that the albuterol dry powder inhaler works well and is safe for use over a long period of time.
Detailed description
The Sponsor terminated this study due to the need for a modification to the Spiromax device utilized in this study; the problem identified has no impact on patient safety. Exposure ranged from 3 to 49 days with the majority of subjects receiving ≤30 days of double-blind treatment.
Interventions
DRUGPlacebo Spiromax
Placebo as a dry-powder inhaled orally using the Spiromax inhaler. During the 12-week double-blind period, participants take two (2) inhalations four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime.
Albuterol as a dry-powder inhaled orally using the Spiromax inhaler. Each inhalation delivers 90 micrograms (mcg). During the 12-week double-blind period, participants take two (2) inhalations four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime for a total dose of 720 micrograms per day for those paricipants randomized to the Albuterol treatment arm. The double-blind period is followed by a 40-week open-label period in which all study participants will take Albuterol Spiromax 90 micrograms (mcg)/inhalation as needed (PRN).
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented history of persistent asthma with rescue use of albuterol on average of at least once/ week over the 4-weeks prior to screening. * Female subjects who are of childbearing potential (as judged by the investigator) must be currently using and willing to continue to use a medically reliable method of contraception for the entire study duration * General good health * Capable of understanding the requirements, risks, and benefits of study participation * Non-smoker for at least one year prior to the screening visit and a maximum pack-year smoking history of 10 years * Other criteria apply
Exclusion criteria
* Pregnancy, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days following the subject's last study related visit * Participation in any investigational drug trial within 30 days preceding the screening visit * A known hypersensitivity to albuterol or any of the excipients in the formulations. * History of severe milk protein allergy * History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc) which is not resolved within 1 week prior to the Screening Visit. * Use of any protocol prohibited concomitant medications for asthma or any protocol prohibited concomitant non-asthma medications * Inability to tolerate or unwillingness to comply with the protocol requirements. * History of life-threatening asthma * Any asthma exacerbation within 3 months of the Screening Visit requiring oral or systemic corticosteroids * History of life-threatening asthma * Other criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent Adverse Events | Day 1 to Day 49 (study termination) | Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol 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 the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include 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 patient and required medical intervention to prevent the previously listed serious outcomes. |
| Changes From Screening in the Results of the Physical Examination That Are Clinically Significant in the Opinion of the Investigator | Days -15 to -8 (Screening), Week 12, Week 52 | A complete physical examination was planned at study screening, week 12 and week 52 or early termination/discontinuation of the participant. At weeks 12 and 52,the qualified healthcare professional was to evaluate whether each physical finding is a new finding, worsening, improvement or resolution of an existing condition compared with the baseline physical exam. Where possible, the same qualified healthcare professional that performed the physical examination at study screening should perform all the scheduled physical examinations. |
| Changes From Screening in the Results of the Laboratory Evaluations That Are Clinically Significant in the Opinion of the Investigator | Days -15 to -8 (Screening), Week 12, Week 52 | Blood samples were to collected for laboratory evaluations at the screening visit and at weeks 12 and 52 or early termination/discontinuation of the participant. The blood samples were to be drawn after an overnight fast of at least 6 hours and analyzed by a central laboratory. |
| Changes From Screening in the Results of the Electrocardiograms (ECGs) That Are Clinically Significant in the Opinion of the Investigator | Days -15 to -8 (Screening), Week 12, Week 52 | A standard 12-lead ECG was to be performed at screening and at week 12 and week 52 (TV15) or early termination/discontinuation of the participant. The ECG recording methods were to be centralized and standardized across all study subjects. |
| Changes From Screening in the Vital Signs That Are Clinically Significant in the Opinion of the Investigator | Days -15 to -8 (Screening), Week 12, Week 52 | Vital sign measurements (heart rate and blood pressure) were to be evaluated as part of the safety profile assessment. The participant was to be seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer could be used. |
Countries
United States
Participant flow
Pre-assignment details
Four hundred fifty-two patients were screened and 331 randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Albuterol Spiromax Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN). | 166 |
| Placebo Spiromax Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN). | 165 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Sponsor terminated study | 161 | 163 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Albuterol Spiromax | Placebo Spiromax | Total |
|---|---|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 14.07 | 38.0 years STANDARD_DEVIATION 14.91 | 37.9 years STANDARD_DEVIATION 14.47 |
| Ethnicity Hispanic | 20 participants | 21 participants | 41 participants |
| Ethnicity Not Hispanic | 146 participants | 144 participants | 290 participants |
| Height | 66.1 inches STANDARD_DEVIATION 3.59 | 65.7 inches STANDARD_DEVIATION 3.86 | 65.9 inches STANDARD_DEVIATION 3.73 |
| Race/Ethnicity, Customized Asian | 4 participants | 1 participants | 5 participants |
| Race/Ethnicity, Customized Black | 19 participants | 28 participants | 47 participants |
| Race/Ethnicity, Customized North American or Alaska Native | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized White | 140 participants | 132 participants | 272 participants |
| Sex: Female, Male Female | 105 Participants | 122 Participants | 227 Participants |
| Sex: Female, Male Male | 61 Participants | 43 Participants | 104 Participants |
| Weight | 184 pounds STANDARD_DEVIATION 49.7 | 179 pounds STANDARD_DEVIATION 48.2 | 182 pounds STANDARD_DEVIATION 48.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 166 | 20 / 165 |
| serious Total, serious adverse events | 1 / 166 | 1 / 165 |
Outcome results
Primary
Changes From Screening in the Results of the Electrocardiograms (ECGs) That Are Clinically Significant in the Opinion of the Investigator
A standard 12-lead ECG was to be performed at screening and at week 12 and week 52 (TV15) or early termination/discontinuation of the participant. The ECG recording methods were to be centralized and standardized across all study subjects.
Time frame: Days -15 to -8 (Screening), Week 12, Week 52
Population: Safety population. The study was terminated prior to the during study evaluations.
Primary
Changes From Screening in the Results of the Laboratory Evaluations That Are Clinically Significant in the Opinion of the Investigator
Blood samples were to collected for laboratory evaluations at the screening visit and at weeks 12 and 52 or early termination/discontinuation of the participant. The blood samples were to be drawn after an overnight fast of at least 6 hours and analyzed by a central laboratory.
Time frame: Days -15 to -8 (Screening), Week 12, Week 52
Population: Safety population. The study was terminated prior to the during study evaluations.
Primary
Changes From Screening in the Results of the Physical Examination That Are Clinically Significant in the Opinion of the Investigator
A complete physical examination was planned at study screening, week 12 and week 52 or early termination/discontinuation of the participant. At weeks 12 and 52,the qualified healthcare professional was to evaluate whether each physical finding is a new finding, worsening, improvement or resolution of an existing condition compared with the baseline physical exam. Where possible, the same qualified healthcare professional that performed the physical examination at study screening should perform all the scheduled physical examinations.
Time frame: Days -15 to -8 (Screening), Week 12, Week 52
Population: Safety population. The study was terminated prior to the during study evaluations.
Primary
Changes From Screening in the Vital Signs That Are Clinically Significant in the Opinion of the Investigator
Vital sign measurements (heart rate and blood pressure) were to be evaluated as part of the safety profile assessment. The participant was to be seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer could be used.
Time frame: Days -15 to -8 (Screening), Week 12, Week 52
Population: Safety population. The study was terminated prior to the during study evaluations.
Primary
Participants With Treatment-Emergent Adverse Events
Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol 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 the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include 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 patient and required medical intervention to prevent the previously listed serious outcomes.
Time frame: Day 1 to Day 49 (study termination)
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Moderate adverse event | 35 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Treatment-related adverse event | 3 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Withdrawn from study due to adverse event | 0 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Serious adverse event | 1 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Treatment-related serious adverse event | 0 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Mild adverse event | 29 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Any adverse event | 59 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Severe adverse event | 2 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Infections and infestations | 31 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Respiratory, thoracic and mediastinal | 12 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Gastrointestinal | 9 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Nervous system | 7 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Injury, poisoning and procedural compli | 4 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Investigations | 3 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Musculoskeletal and connective tissue | 2 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Renal and urinary | 2 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Ear and labyrinth | 2 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Skin and subcutaneous tissue | 2 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: General and administrative site conditi | 1 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Psychiatric | 1 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Social circumstances | 1 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Cardiac | 0 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Eye | 0 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Blood and lymphatic system | 0 participants |
| Albuterol Spiromax | Participants With Treatment-Emergent Adverse Events | Neoplasm benign, malignant + unspecified | 0 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Injury, poisoning and procedural compli | 2 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Any adverse event | 58 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: General and administrative site conditi | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Treatment-related adverse event | 3 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Investigations | 3 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Withdrawn from study due to adverse event | 0 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Cardiac | 2 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Serious adverse event | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Musculoskeletal and connective tissue | 4 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Treatment-related serious adverse event | 0 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Psychiatric | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Mild adverse event | 32 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Renal and urinary | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Moderate adverse event | 29 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Neoplasm benign, malignant + unspecified | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | Severe adverse event | 4 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Blood and lymphatic system | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Infections and infestations | 34 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Ear and labyrinth | 1 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Respiratory, thoracic and mediastinal | 11 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Social circumstances | 0 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Gastrointestinal | 5 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Skin and subcutaneous tissue | 0 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Nervous system | 6 participants |
| Placebo Spiromax | Participants With Treatment-Emergent Adverse Events | AE class: Eye | 1 participants |
Post Hoc
Blood Pressure at Screening and End of Study
Vital sign measurements (heart rate and blood pressure) were evaluated as part of the safety profile assessment. The participant was seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer was used.
Time frame: Days -15 to -8 (Screening), up to Day 49 (End of study)
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol Spiromax | Blood Pressure at Screening and End of Study | Screening Diastolic BP (n=166, 165) | 75.5 mmHg | Standard Deviation 9.24 |
| Albuterol Spiromax | Blood Pressure at Screening and End of Study | End of Study Diastolic BP (n=164, 164) | 75.7 mmHg | Standard Deviation 9.54 |
| Albuterol Spiromax | Blood Pressure at Screening and End of Study | Screening Systolic BP (n=166, 165) | 119.4 mmHg | Standard Deviation 13.39 |
| Albuterol Spiromax | Blood Pressure at Screening and End of Study | End of Study Systolic BP (n=164, 164) | 118.4 mmHg | Standard Deviation 13.5 |
| Placebo Spiromax | Blood Pressure at Screening and End of Study | End of Study Systolic BP (n=164, 164) | 118.2 mmHg | Standard Deviation 12.99 |
| Placebo Spiromax | Blood Pressure at Screening and End of Study | Screening Diastolic BP (n=166, 165) | 75.2 mmHg | Standard Deviation 9.08 |
| Placebo Spiromax | Blood Pressure at Screening and End of Study | Screening Systolic BP (n=166, 165) | 118.0 mmHg | Standard Deviation 13.7 |
| Placebo Spiromax | Blood Pressure at Screening and End of Study | End of Study Diastolic BP (n=164, 164) | 75.2 mmHg | Standard Deviation 8.79 |
Post Hoc
Pulse at Screening and End of Study
Vital sign measurements (heart rate and blood pressure) were evaluated as part of the safety profile assessment. The participant was seated at least 2 minutes before vital signs were performed. Heart rate was measured by radial pulse.
Time frame: Days -15 to -8 (Screening), up to Day 49 (End of study)
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol Spiromax | Pulse at Screening and End of Study | Screening (n=166, 165) | 71.0 beats/minute | Standard Deviation 8.57 |
| Albuterol Spiromax | Pulse at Screening and End of Study | End of study (n=164, 164) | 72.1 beats/minute | Standard Deviation 9.34 |
| Placebo Spiromax | Pulse at Screening and End of Study | Screening (n=166, 165) | 71.8 beats/minute | Standard Deviation 10.03 |
| Placebo Spiromax | Pulse at Screening and End of Study | End of study (n=164, 164) | 73.0 beats/minute | Standard Deviation 9.48 |