Asthma
Conditions
Brief summary
The purpose of this study is to evaluate the safety of Albuterol Spiromax® over 52 weeks during two dosing periods: (1) a 12-week, double-blind, placebo-controlled QID dosing period followed by (2) a 40-week, open-label PRN dosing period, and to evaluate Albuterol Spiromax® device performance through the life of the device during the study.
Interventions
DRUGPlacebo MDPI
Placebo MDPI (multi-dose dry powder inhaler) to match the active intervention.
DRUGAlbuterol MDPI
Albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation.
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
* Written informed consent and HIPAA signed and dated by the subject or written informed assent signed and dated both by the subject and/or parent/caregiver/legal guardian before conducting any study related procedure. * Males or females with asthma ages 12 years or older at screening. * Documented history of persistent asthma and current use of an MDI containing any short-acting beta-adrenergic agonist (e.g. albuterol, levalbuterol,) on average of at least once/week over the 4-weeks prior to screening. The asthma diagnosis must be consistent with the diagnosis of asthma as per the National Asthma Education and Prevention Program. * If female, is currently not pregnant, breast feeding, or attempting to become pregnant (for 4 weeks before the screening visit and throughout the duration of the study), and is of Non-childbearing potential, defined as: * ≥1 year post-menopausal or * Surgically sterile (tubal ligation, bilateral oophorectomy, salpingectomy, or hysterectomy) or is of * Childbearing potential, has a negative serum pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control * General good health in the opinion of the investigator as indicated by medical history, physical examination, laboratory tests (hematology, serum chemistry and urinalysis) assessed as either normal or abnormal not clinically significant (NCS) per the principal investigator, as well as a 12-lead ECG interpreted as either Normal or Abnormal NCS as determined by the central cardiologist. Subjects must also be free of any clinically significant, uncontrolled concomitant conditions other than asthma that could interfere with study conduct, influence the interpretation of study observations/results, or put the subject at increased risk during the trial. * Capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, and being compliant with all study requirements (visits, record-keeping, etc). * Non-smoker for at least one year prior to the screening visit and a maximum pack-year (PY) smoking history of 10 years. * Able to demonstrate proper inhaler technique with study inhaler.
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 or planned participation in another investigational drug trial at any time during this trial. * A known hypersensitivity to albuterol or any of the excipients in the formulations. * History of severe milk protein allergy * History of an upper or lower respiratory tract infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc) which is not resolved at least 1 week prior to the SV. * History of alcohol or drug abuse within two years preceding the SV. * Use of any protocol prohibited concomitant medications for asthma (any oral β2-adrenergic agonists) or any protocol prohibited concomitant non-asthma medications including treatment with β2-adrenergic receptor antagonists and non-selective β-receptor blocking agents such as β-blocking anti-hypertensive products (administered by any route), MAO inhibitors, and/or tricyclic antidepressants. (Subject's own MDI short-acting β-agonist rescue inhaler should be used until the start of the Run-In period when a study rescue inhaler is provided.) * Inability or unwillingness to comply with the protocol requirements. * History of life-threatening asthma \[defined here as an asthma episode requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures.\] * Any asthma exacerbation within 3 months of the SV requiring oral or systemic corticosteroids or any hospitalization for asthma within 6 months of the SV. Note: An exacerbation of asthma is defined as any worsening of asthma requiring any treatment other than rescue albuterol or the subject's regular asthma maintenance therapy. This includes requiring the use of systemic corticosteroids and/or emergency room visit or hospitalization or a change in subject's regular asthma maintenance treatment. A subject does not need to be withdrawn from the study due to an asthma exacerbation unless hospitalization is required or unless the principal investigator believes it is in the subjects' best interest to withdraw from the study. * Previous participation in an inhaled Albuterol Spiromax® (Teva) study, with the exception of the ABS-AS-306 study. * Study participation by clinical investigator site employees and/or their immediate relatives. * Study participation by related or non-related individuals living in the same household, i.e. only one subject per household may participate in the study. * Any clinically significant endocrine, hematological, hepatic, renal, gastrointestinal, neurological, cardiac, metabolic, immunological, any non-asthmatic acute or chronic pulmonary condition (including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis), and malignancy other than basal cell carcinoma. Significant is defined for this protocol as any condition that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which could affect the safety analyses. * Any medical or psychological condition that in the investigator's opinion should preclude enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Weeks 0, 12 and 52 | The physical exam was performed by a qualified healthcare professional, and when possible, the same qualified healthcare professional that performed the physical examination at study screening performed all the scheduled physical examinations. Abnormalities and clinical relevance were determined by the qualified healthcare professional. HEENT = head, eyes, ears, nose, throat |
| Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Weeks 0 (screening visit), 12, and 52 | A standard 12-lead ECG was performed at screening, week 12, and week 52 or early termination/discontinuation. The ECG recording methods were centralized and standardized across all study participants. A centralized cardiologist was responsible for providing all ECG interpretations. |
| Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Week 0, Week 12 and Week 52 | Participants were seated at least 2 minutes before blood pressure measurements were obtained by either an electronic or manual sphygmomanometer. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12. |
| Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Week 0, Week 12 and Week 52 | Participants were seated at least 2 minutes before pulse measurements were obtained by radial pulse. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12. |
| Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Day 1 to Week 12 | 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. |
| Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Weeks 13-52 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Device Invitro Evaluations to Week 52 | Baseline to Week 52 | Device In Vitro Evaluations - All used study inhalers will be collected and a random selection of inhalers will be tested as follows: * Fifty (50) Albuterol Spiromax® inhalers used during weeks 0-12 will be randomly selected for in vitro testing * Fifty (50) Albuterol Spiromax® inhalers used during weeks 12-52 will be randomly selected for in vitro performance testing |
| Daily AM Peak Expiratory Flow (PEF) to Week 52 | Baseline to Week 52 | Daily AM PEF will be recorded throughout the duration of the study to provide information on the subject's asthma status in order to assist in distinguishing between the use of back-up rescue medication related to an increased need for asthma symptom relief from that related to an issue with the Albuterol Spiromax® rescue inhaler. |
| Composite Measurement of Device Ruggedness From Baseline to Week 52 | Baseline to Week 52 | Device Ruggedness: Reports of any problems/malfunction of the device (e.g., lack of efficacy, problems/malfunction after the device is dropped or sustains physical impact). |
Countries
United States
Participant flow
Pre-assignment details
Of the 33 patients who were screened but not enrolled, 28 were excluded on the basis of inclusion/exclusion criteria, 2 patients withdrew consent, and 3 patients were lost to follow-up before the baseline visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo MDPI-Albuterol MDPI During the 12-week double-blind period, participants take 2 inhalations of placebo MDPI (multi-dose dry powder inhaler), four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime.
The double-blind period is followed by a 40-week open-label period in which all study participants take albuterol MDPI 90 micrograms/inhalation, 2 inhalations every 4-6 hours as needed (PRN) and, if applicable, 2 inhalations 15-30 minutes prior to sports/exercise. | 169 |
| Albuterol MDPI-Albuterol MDPI During the 12-week double-blind period, participants take 2 inhalations of albuterol MDPI (multi-dose dry powder inhaler or Spiromax®) 90 mcg/inhalation, four times a day (QID) at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime for a total daily dose of 720 micrograms per day.
The double-blind period is followed by a 40-week open-label period in which all study participants take albuterol MDPI 90 micrograms/inhalation, 2 inhalations every 4-6 hours as needed (PRN) and, if applicable, 2 inhalations 15-30 minutes prior to sports/exercise. | 168 |
| Total | 337 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 12-Week Double-Blind Period | Adverse Event | 0 | 1 | 1 |
| 12-Week Double-Blind Period | Lost to Follow-up | 0 | 0 | 4 |
| 12-Week Double-Blind Period | Pregnancy | 0 | 1 | 1 |
| 12-Week Double-Blind Period | Protocol Violation | 0 | 0 | 2 |
| 12-Week Double-Blind Period | Sponsor requested subject withdrawal | 0 | 0 | 2 |
| 12-Week Double-Blind Period | Withdrawal by Subject | 0 | 2 | 2 |
| 40-Week Open-Label Period | Adverse Event | 0 | 3 | 2 |
| 40-Week Open-Label Period | Lost to Follow-up | 0 | 2 | 0 |
| 40-Week Open-Label Period | Pregnancy | 0 | 2 | 1 |
| 40-Week Open-Label Period | Sponsor requested subject withdrawal | 0 | 1 | 0 |
| 40-Week Open-Label Period | Withdrawal by Subject | 0 | 11 | 7 |
| Run-In Period (Week -1 to Day 0) | Inclusion/exclusion criteria | 24 | 0 | 0 |
| Run-In Period (Week -1 to Day 0) | Lost to Follow-up | 1 | 0 | 0 |
| Run-In Period (Week -1 to Day 0) | Other | 1 | 0 | 0 |
| Run-In Period (Week -1 to Day 0) | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo MDPI-Albuterol MDPI | Albuterol MDPI-Albuterol MDPI | Total |
|---|---|---|---|
| Age, Continuous | 37.1 years STANDARD_DEVIATION 15.14 | 36.6 years STANDARD_DEVIATION 15.04 | 36.8 years STANDARD_DEVIATION 15.07 |
| Age, Customized 12-17 years | 19 participants | 25 participants | 44 participants |
| Age, Customized 18-64 years | 143 participants | 135 participants | 278 participants |
| Age, Customized 65+ years | 7 participants | 8 participants | 15 participants |
| Body Mass Index | 29.2 kg/m^2 STANDARD_DEVIATION 6.96 | 28.5 kg/m^2 STANDARD_DEVIATION 6.81 | 28.8 kg/m^2 STANDARD_DEVIATION 6.88 |
| Height | 167.4 cm STANDARD_DEVIATION 8.67 | 168.6 cm STANDARD_DEVIATION 9.52 | 168.0 cm STANDARD_DEVIATION 9.11 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Black | 35 participants | 38 participants | 73 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 25 participants | 28 participants | 53 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 144 participants | 140 participants | 284 participants |
| Race/Ethnicity, Customized Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 129 participants | 125 participants | 254 participants |
| Sex: Female, Male Female | 111 Participants | 103 Participants | 214 Participants |
| Sex: Female, Male Male | 58 Participants | 65 Participants | 123 Participants |
| Weight | 82.3 kg STANDARD_DEVIATION 21.09 | 81.2 kg STANDARD_DEVIATION 21.4 | 81.8 kg STANDARD_DEVIATION 21.22 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 51 / 168 | 80 / 170 | 64 / 169 | 67 / 168 |
| serious Total, serious adverse events | 0 / 168 | 1 / 170 | 3 / 169 | 4 / 168 |
Outcome results
Primary
Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52
Participants were seated at least 2 minutes before blood pressure measurements were obtained by either an electronic or manual sphygmomanometer. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.
Time frame: Week 0, Week 12 and Week 52
Population: Safety population. Participants with assessments at each time point are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Systolic BP Week 12 (n=166, 155) | 1.0 mmHg | Standard Deviation 11.27 |
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Systolic BP Week 52 (n=159, 155) | -0.4 mmHg | Standard Deviation 11.54 |
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Diastolic BP Week 12 (n=166, 155) | 0.0 mmHg | Standard Deviation 9.16 |
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Diastolic BP Week 52 (n=159, 155) | 0.2 mmHg | Standard Deviation 9.14 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Diastolic BP Week 52 (n=159, 155) | 1.0 mmHg | Standard Deviation 8.15 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Systolic BP Week 12 (n=166, 155) | 0.2 mmHg | Standard Deviation 10.99 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Diastolic BP Week 12 (n=166, 155) | 0.3 mmHg | Standard Deviation 7.62 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Blood Pressure Measurements to Week 12 and Week 52 | Systolic BP Week 52 (n=159, 155) | 0.7 mmHg | Standard Deviation 10.31 |
Primary
Change From Baseline in Pulse Measurements to Week 12 and Week 52
Participants were seated at least 2 minutes before pulse measurements were obtained by radial pulse. Week 12 values represent change from Week 0. Week 52 values represent change from Week 12.
Time frame: Week 0, Week 12 and Week 52
Population: Safety population. Participants with assessments at each time point are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Pulse Week 12 (n=166, 155) | -0.1 beats/minute | Standard Deviation 9.4 |
| Placebo MDPI-Albuterol MDPI | Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Pulse Week 52 (n=159, 155) | -0.4 beats/minute | Standard Deviation 10.08 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Pulse Week 12 (n=166, 155) | 0.9 beats/minute | Standard Deviation 9.53 |
| Albuterol MDPI-Albuterol MDPI | Change From Baseline in Pulse Measurements to Week 12 and Week 52 | Pulse Week 52 (n=159, 155) | -0.3 beats/minute | Standard Deviation 9.77 |
Primary
Electrocardiogram (ECG) Results At Weeks 0, 12, and 52
A standard 12-lead ECG was performed at screening, week 12, and week 52 or early termination/discontinuation. The ECG recording methods were centralized and standardized across all study participants. A centralized cardiologist was responsible for providing all ECG interpretations.
Time frame: Weeks 0 (screening visit), 12, and 52
Population: Safety population. Participants with assessments at each time point are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Abnormal, not clinically relevant | 23 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Abnormal, clinically relevant | 0 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Abnormal, clinically relevant | 0 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Abnormal, not clinically relevant | 19 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Normal (n=152, 161) | 138 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Abnormal, not clinically relevant | 23 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Normal (n=166, 155) | 143 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Abnormal, clinically relevant | 1 participants |
| Placebo MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Normal | 151 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Abnormal, clinically relevant | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Normal | 154 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Abnormal, not clinically relevant | 14 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 0: Abnormal, clinically relevant | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Normal (n=166, 155) | 140 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Abnormal, not clinically relevant | 15 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 12: Abnormal, clinically relevant | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Abnormal, not clinically relevant | 13 participants |
| Albuterol MDPI-Albuterol MDPI | Electrocardiogram (ECG) Results At Weeks 0, 12, and 52 | Week 52: Normal (n=152, 161) | 148 participants |
Primary
Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52
The physical exam was performed by a qualified healthcare professional, and when possible, the same qualified healthcare professional that performed the physical examination at study screening performed all the scheduled physical examinations. Abnormalities and clinical relevance were determined by the qualified healthcare professional. HEENT = head, eyes, ears, nose, throat
Time frame: Weeks 0, 12 and 52
Population: Safety population. Participants with assessments at each time point are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 120 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 52 (n=162, 161) | 3 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 0 (n=170, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 12 (n=167, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 0 (n=169, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 0 (n=170, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 12 (n=166, 155) | 1 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 0 (n=170, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 12 (n=166, 155) | 1 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 0 (n=170, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 12 (n=166, 155) | 1 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 12 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 0 (n=168, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 12 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 0 (n=169, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 12 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 0 (n=169, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 0 (n=169, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 52 (n=162, 161) | 2 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 12 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 52 (n=162, 161) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 0 (n=169, 167) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 12 (n=166, 155) | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 52 (n=162, 160) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 52 (n=162, 161) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 0 (n=168, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 52 (n=162, 161) | 2 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 120 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 52 (n=162, 161) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 0 (n=169, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Abdomen - Week 52 (n=162, 161) | 1 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 52 (n=162, 161) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 0 (n=170, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Musculoskeletal - Week 0 (n=169, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 0 (n=169, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | General appearance - Week 52 (n=162, 161) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 0 (n=169, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 0 (n=170, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 12 (n=167, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 12 (n=166, 155) | 1 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | HEENT - Week 52 (n=162, 161) | 2 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Neurological - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 0 (n=170, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Skin - Week 52 (n=162, 161) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Chest and lungs - Week 12 (n=166, 155) | 1 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 0 (n=170, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Extremities/back - Week 52 (n=162, 160) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 12 (n=166, 155) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Lymph Nodes - Week 0 (n=169, 167) | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Abnormal and Clinically Relevant Physical Exam Findings at Weeks 0, 12 and 52 | Heart - Week 52 (n=162, 161) | 0 participants |
Primary
Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period)
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 Week 12
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Other serious adverse events | 1 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Any adverse event | 105 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Severe adverse event | 6 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Treatment-related adverse event | 1 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Deaths | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Withdrawn from treatment due to adverse events | 1 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Deaths | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Other serious adverse events | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Treatment-related adverse event | 5 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Any adverse event | 84 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Withdrawn from treatment due to adverse events | 1 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 0-12 (Double-Blind Period) | Severe adverse event | 3 participants |
Primary
Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period)
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: Weeks 13-52
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Deaths | 0 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Severe adverse event | 12 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Other serious adverse events | 3 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Any adverse event | 106 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Withdrawn from treatment due to adverse events | 2 participants |
| Placebo MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Treatment-related adverse event | 2 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Withdrawn from treatment due to adverse events | 2 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Any adverse event | 94 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Severe adverse event | 13 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Deaths | 0 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Other serious adverse events | 4 participants |
| Albuterol MDPI-Albuterol MDPI | Participants With Adverse Experiences During Weeks 13-52 (Open-Label Period) | Treatment-related adverse event | 1 participants |
Other Pre-specified
Composite Measurement of Device Ruggedness From Baseline to Week 52
Device Ruggedness: Reports of any problems/malfunction of the device (e.g., lack of efficacy, problems/malfunction after the device is dropped or sustains physical impact).
Time frame: Baseline to Week 52
Other Pre-specified
Daily AM Peak Expiratory Flow (PEF) to Week 52
Daily AM PEF will be recorded throughout the duration of the study to provide information on the subject's asthma status in order to assist in distinguishing between the use of back-up rescue medication related to an increased need for asthma symptom relief from that related to an issue with the Albuterol Spiromax® rescue inhaler.
Time frame: Baseline to Week 52
Other Pre-specified
Device Invitro Evaluations to Week 52
Device In Vitro Evaluations - All used study inhalers will be collected and a random selection of inhalers will be tested as follows: * Fifty (50) Albuterol Spiromax® inhalers used during weeks 0-12 will be randomly selected for in vitro testing * Fifty (50) Albuterol Spiromax® inhalers used during weeks 12-52 will be randomly selected for in vitro performance testing
Time frame: Baseline to Week 52