Asthma
Conditions
Brief summary
This study is examining how well a dry powder inhaler (DPI) of albuterol medication works to help adult and adolescent subjects 12 years of age and older with persistent asthma to improve lung function.
Interventions
Albuterol Spiromax® delivers 90 mcg albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.
DRUGProAir® HFA
ProAir® HFA delivers 90 mcg of albuterol per inhalation. Doses of 180 mcg require two inhalations. Intervention given as double-blind medication on 2 of 5 treatment days, once at 90 mcg and once at 180 mcg.
OTHERPlacebo Inhaler
Placebo delivered in both the Spiromax® and HFA inhalers to maintain the blind and also to support the placebo treatment arm.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must provide written informed consent, * Be between 12 years of age and older, * Male or Female, females of non-child bearing potential or using reliable contraception * Asthma for at least 6 months, FEV1 (forced expiratory volume in 1 second) between 50-80% of predicted value, and reversibility greater than or equal to 15% following 180 mcg albuterol * Stable low dose of Inhaled Corticosteroids * Non-smoker, 12 months smoking-free and \<=10-pack years history * Otherwise healthy * Other criteria apply
Exclusion criteria
* Pregnant * Allergic to albuterol or severe milk protein allergy * Must not be on another trial for 30days. * Other criteria apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | Day 1 up to Day 30 | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | Day 1 up to Day 30 | Percent-predicted FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. Percent-predicted FEV1 is the expected FEV1 taking into account age, height, gender and race, as per the National Health and Nutrition Examination Survey III (NHANES III) reference values. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing. |
| Participants With Treatment-Emergent Adverse Events | Day 1 up to Day 37 | 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. 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 163 patients were screened and 72 patients were randomized. Most screening failures did not qualify for the study based on reversibility or spirometry criteria.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Treated Participants Participants were randomized to one of ten treatment sequences, which indicated the order of the 5 single-dose treatments administered in this 5-way crossover study. | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Randomized in error | 1 |
| Overall Study | Sponsor requested withdrawal | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Randomized Treated Participants |
|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 14.78 |
| Age, Customized 12 to <18 years | 3 participants |
| Age, Customized 18 to 65 years | 64 participants |
| Age, Customized >65 years | 4 participants |
| Height | 169.1 cm STANDARD_DEVIATION 9.49 |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Black or African American | 16 participants |
| Race/Ethnicity, Customized Latino or Hispanic | 4 participants |
| Race/Ethnicity, Customized Not Latino or Hispanic | 67 participants |
| Race/Ethnicity, Customized White | 54 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 30 Participants |
| Weight | 89.6 kg STANDARD_DEVIATION 22.77 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 68 | 3 / 68 | 0 / 70 | 2 / 68 | 2 / 69 |
| serious Total, serious adverse events | 0 / 68 | 0 / 68 | 0 / 70 | 0 / 68 | 0 / 69 |
Outcome results
Primary
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6)
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing.
Time frame: Day 1 up to Day 30
Population: Intent to treat population: randomized participants who received at least 1 dose of randomized study medication and had at least 1 post-baseline assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol Spiromax® 90 mcg | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | 1.21 L*hour | Standard Error 0.224 |
| Albuterol Spiromax® 180 mcg | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | 1.39 L*hour | Standard Error 0.224 |
| ProAir® HFA 90 mcg | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | 1.12 L*hour | Standard Error 0.223 |
| ProAir® HFA 180 mcg | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | 1.33 L*hour | Standard Error 0.224 |
| Placebo Inhaler | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) | 0.24 L*hour | Standard Error 0.224 |
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [0.88, 1.42]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [0.7, 1.24]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level..p-value: <0.000195% CI: [0.81, 1.35]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [0.61, 1.15]ANOVA
Secondary
Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6)
Percent-predicted FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. Percent-predicted FEV1 is the expected FEV1 taking into account age, height, gender and race, as per the National Health and Nutrition Examination Survey III (NHANES III) reference values. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing.
Time frame: Day 1 up to Day 30
Population: Intent to treat population: randomized participants who received at least 1 dose of randomized study medication and had at least 1 post-baseline assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol Spiromax® 90 mcg | Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | 35.31 % predicted * hour | Standard Error 4.497 |
| Albuterol Spiromax® 180 mcg | Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | 41.05 % predicted * hour | Standard Error 4.495 |
| ProAir® HFA 90 mcg | Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | 33.19 % predicted * hour | Standard Error 4.461 |
| ProAir® HFA 180 mcg | Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | 40.68 % predicted * hour | Standard Error 4.496 |
| Placebo Inhaler | Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6) | 7.58 % predicted * hour | Standard Error 4.482 |
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [26.21, 40.74]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.00195% CI: [20.47, 34.99]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [25.84, 40.35]ANOVA
Comparison: Of interest was the mean difference between each active group and placebo at each dose level. Analyses were performed at the 2-sided 0.05 significance level in this sequence: Albuterol Spiromax 180 mcg versus placebo; Albuterol Spiromax 90 mcg versus placebo, ProAir HFA 180 mcg versus placebo, and ProAir HFA 90 mcg versus placebo. If a test was not significant, no further tests were done. This sequential procedure preserved the error rate for the family of tests at the 0.05 level.p-value: <0.000195% CI: [18.36, 32.85]ANOVA
Secondary
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. 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 up to Day 37
Population: Safety population of all randomized participants who received at least one dose of randomized study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related serious AE | 0 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Any adverse event | 9 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 0 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Withdrawn from study due to AEs | 0 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Any serious AEs | 0 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Onset treatment for AE: Placebo Inhaler | 2 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Onset treatment for AE: Albuterol Spiromax 90mcg | 3 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Onset treatment for AE: Albuterol Spiromax 180mcg | 3 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Onset treatment for AE: ProAir HFA 90 mcg | 0 participants |
| Albuterol Spiromax® 90 mcg | Participants With Treatment-Emergent Adverse Events | Onset treatment for AE: ProAir HFA 180 mcg | 2 participants |