Trial Outcomes & Findings for Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients (NCT NCT01899144)
NCT ID: NCT01899144
Last Updated: 2022-01-26
Results Overview
Percent predicted FEV1: measured FEV1 as a percent of the "predicted values" for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination.
COMPLETED
PHASE2
61 participants
Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati
2022-01-26
Participant Flow
Of the 102 patients screened, 61 patients at 14 centers in the US met entry criteria and were considered to be eligible for enrollment into the study. 41 patients were not enrolled: 33 were excluded due to inclusion criteria, 1 patient withdrew consent, 3 patients were lost to follow-up before the baseline visit, and 4 patients for other reasons.
Participants were randomized in a 1:1:1:1:1:1:1:1:1:1 fashion into 10 treatment sequences with 6 participants in 9 of the sequences and 7 participants in the remaining sequence.
Participant milestones
| Measure |
All Participants
Participants were assigned to 1 of 10 possible treatment sequences for five treatments, separated by 2-7 days. Treatments were single inhalations of Albuterol MDPI 90 mcg, Albuterol MDPI 180 mcg, ProAir HFA MDI 90 mcg, ProAir HFA MDI 180 mcg, and placebo.
|
|---|---|
|
Treatment Period 1
STARTED
|
61
|
|
Treatment Period 1
COMPLETED
|
61
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
|
Treatment Period 2
STARTED
|
61
|
|
Treatment Period 2
COMPLETED
|
60
|
|
Treatment Period 2
NOT COMPLETED
|
1
|
|
Treatment Period 3
STARTED
|
60
|
|
Treatment Period 3
COMPLETED
|
58
|
|
Treatment Period 3
NOT COMPLETED
|
2
|
|
Treatment Period 4
STARTED
|
58
|
|
Treatment Period 4
COMPLETED
|
58
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
|
Treatment Period 5
STARTED
|
58
|
|
Treatment Period 5
COMPLETED
|
57
|
|
Treatment Period 5
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
All Participants
Participants were assigned to 1 of 10 possible treatment sequences for five treatments, separated by 2-7 days. Treatments were single inhalations of Albuterol MDPI 90 mcg, Albuterol MDPI 180 mcg, ProAir HFA MDI 90 mcg, ProAir HFA MDI 180 mcg, and placebo.
|
|---|---|
|
Treatment Period 2
Other
|
1
|
|
Treatment Period 3
Other
|
2
|
|
Treatment Period 5
Other
|
1
|
Baseline Characteristics
Efficacy and Safety Comparison of Albuterol Spiromax® and ProAir® Hydrofluoroalkane (HFA) in Pediatric Patients
Baseline characteristics by cohort
| Measure |
All Participants
n=61 Participants
Participants were assigned to 1 of 10 possible treatment sequences for five treatments, separated by 2-7 days. Treatments were single inhalations of Albuterol MDPI 90 mcg, Albuterol MDPI 180 mcg, ProAir HFA MDI 90 mcg, ProAir HFA MDI 180 mcg, and placebo.
|
|---|---|
|
Age, Continuous
|
9.0 years
STANDARD_DEVIATION 1.6 • n=39 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=39 Participants
|
|
Race/Ethnicity, Customized
White
|
28 participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Black
|
29 participants
n=39 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=39 Participants
|
|
Weight
|
38.2 kg
STANDARD_DEVIATION 12.8 • n=39 Participants
|
|
Height
|
138.7 cm
STANDARD_DEVIATION 10.2 • n=39 Participants
|
|
Body Mass Index
|
19.5 kg/m^2
STANDARD_DEVIATION 4.35 • n=39 Participants
|
|
Duration of Asthma
None
|
0 participants
n=39 Participants
|
|
Duration of Asthma
<3 months
|
0 participants
n=39 Participants
|
|
Duration of Asthma
3 to <6 months
|
0 participants
n=39 Participants
|
|
Duration of Asthma
6 months to <1 year
|
1 participants
n=39 Participants
|
|
Duration of Asthma
1 to <5 years
|
22 participants
n=39 Participants
|
|
Duration of Asthma
5 to <10 years
|
30 participants
n=39 Participants
|
|
Duration of Asthma
10 to <15 years
|
8 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
None
|
46 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
<3 months
|
2 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
3 to <6 months
|
1 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
6 months to <1 year
|
3 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
1 to <5 years
|
9 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
5 to <10 years
|
0 participants
n=39 Participants
|
|
Duration of Previous Dry-Powder Inhaler (DPI) Experience
10 to <15 years
|
0 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
None
|
1 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
<3 months
|
1 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
3 to <6 months
|
0 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
6 months to <1 year
|
3 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
1 to <5 years
|
34 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
5 to <10 years
|
19 participants
n=39 Participants
|
|
Duration of Previous Metered-Dose Inhaler (MDI) Experience
10 to <15 years
|
3 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administratiPopulation: Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of study medication, had a baseline assessment, and had at least 1 post baseline assessment.
Percent predicted FEV1: measured FEV1 as a percent of the "predicted values" for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination.
Outcome measures
| Measure |
Albuterol Spiromax 90 mcg
n=58 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the DPIs contains Albuterol Spiromax 90 mcg; the other three devices contained placebo.
|
Albuterol Spiromax 180 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the DPIs contain Albuterol Spiromax 90 mcg for a total dose of 180 mcg; the MDIs contained placebo.
|
ProAir HFA 90 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the MDIs contains ProAir HFA 90 mcg; the other three devices contained placebo.
|
ProAir HFA 180 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the MDIs contain ProAir HFA 90 mcg for a total dose of 180 mcg; the DPIs contained placebo.
|
Placebo
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, all devices contain placebo.
|
|---|---|---|---|---|---|
|
Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose
|
46.6 %predicted FEV1*hour
Standard Error 6.27
|
48.0 %predicted FEV1*hour
Standard Error 6.24
|
37.9 %predicted FEV1*hour
Standard Error 6.25
|
49.1 %predicted FEV1*hour
Standard Error 6.26
|
25.4 %predicted FEV1*hour
Standard Error 6.25
|
SECONDARY outcome
Timeframe: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administratiPopulation: Full analysis set
FEV1 AUC0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose FEV1 values from each post-dose FEV1 determination.
Outcome measures
| Measure |
Albuterol Spiromax 90 mcg
n=58 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the DPIs contains Albuterol Spiromax 90 mcg; the other three devices contained placebo.
|
Albuterol Spiromax 180 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the DPIs contain Albuterol Spiromax 90 mcg for a total dose of 180 mcg; the MDIs contained placebo.
|
ProAir HFA 90 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the MDIs contains ProAir HFA 90 mcg; the other three devices contained placebo.
|
ProAir HFA 180 mcg
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the MDIs contain ProAir HFA 90 mcg for a total dose of 180 mcg; the DPIs contained placebo.
|
Placebo
n=59 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, all devices contain placebo.
|
|---|---|---|---|---|---|
|
Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6)
|
0.88 L*hour
Standard Error 0.14
|
0.93 L*hour
Standard Error 0.14
|
0.74 L*hour
Standard Error 0.14
|
0.93 L*hour
Standard Error 0.14
|
0.48 L*hour
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Day 1 up to Day 35Population: The safety population included all randomized patients who received at least 1 dose of randomized study medication. In this population, treatment was assigned based upon the treatment patients actually receive regardless of the treatment to which they were randomized.
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 as mild (no limitation of usual activities), moderate, or severe (inability to carry out usual 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.
Outcome measures
| Measure |
Albuterol Spiromax 90 mcg
n=61 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the DPIs contains Albuterol Spiromax 90 mcg; the other three devices contained placebo.
|
Albuterol Spiromax 180 mcg
n=61 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the DPIs contain Albuterol Spiromax 90 mcg for a total dose of 180 mcg; the MDIs contained placebo.
|
ProAir HFA 90 mcg
n=61 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the MDIs contains ProAir HFA 90 mcg; the other three devices contained placebo.
|
ProAir HFA 180 mcg
n=61 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the MDIs contain ProAir HFA 90 mcg for a total dose of 180 mcg; the DPIs contained placebo.
|
Placebo
n=61 Participants
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, all devices contain placebo.
|
|---|---|---|---|---|---|
|
Participants With Treatment-Emergent Adverse Events
Treatment-related AE
|
0 participants
|
2 participants
|
5 participants
|
1 participants
|
1 participants
|
|
Participants With Treatment-Emergent Adverse Events
Related TEAE
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participants With Treatment-Emergent Adverse Events
Death
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participants With Treatment-Emergent Adverse Events
Serious AE
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participants With Treatment-Emergent Adverse Events
Severe TEAE
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Participants With Treatment-Emergent Adverse Events
TEAE leading to withdrawal
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Albuterol Spiromax 90 mcg
Albuterol Spiromax 180 mcg
ProAir HFA 90 mcg
ProAir HFA 180 mcg
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Albuterol Spiromax 90 mcg
n=61 participants at risk
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the DPIs contains Albuterol Spiromax 90 mcg; the other three devices contained placebo.
|
Albuterol Spiromax 180 mcg
n=61 participants at risk
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the DPIs contain Albuterol Spiromax 90 mcg for a total dose of 180 mcg; the MDIs contained placebo.
|
ProAir HFA 90 mcg
n=61 participants at risk
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, one of the MDIs contains ProAir HFA 90 mcg; the other three devices contained placebo.
|
ProAir HFA 180 mcg
n=61 participants at risk
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind.
In this arm, both of the MDIs contain ProAir HFA 90 mcg for a total dose of 180 mcg; the DPIs contained placebo.
|
Placebo
n=61 participants at risk
At each treatment visit, participants receive 1 actuation from each of 4 pre-arranged device combinations comprising 2 dry powder inhalers (DPIs) and 2 metered-dose inhalers (MDIs) in order to maintain the study blind. In this arm, all devices contain placebo.
|
|---|---|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/61 • Day 1 up to Day 35
|
0.00%
0/61 • Day 1 up to Day 35
|
4.9%
3/61 • Day 1 up to Day 35
|
0.00%
0/61 • Day 1 up to Day 35
|
0.00%
0/61 • Day 1 up to Day 35
|
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER