Trial Outcomes & Findings for Efficacy of Inhaled Albuterol Spiromax® in Subjects With Persistent Asthma With Steady State Pharmacokinetics (NCT NCT01747629)
NCT ID: NCT01747629
Last Updated: 2015-06-26
Results Overview
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
COMPLETED
PHASE3
160 participants
Day 1, Day 8 and Day 85
2015-06-26
Participant Flow
Of the 361 patients screened, 158 were excluded on the basis of inclusion criteria, 5 on the basis of exclusion criteria, 13 withdrew consent, 1 patient was noncompliant, 2 patients were lost to follow-up before the baseline visit, 7 patients had other reasons, and 15 failed to meet the randomization criteria at the end of the run-in period.
Participant milestones
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
85
|
75
|
|
Overall Study
Treated
|
84
|
75
|
|
Overall Study
COMPLETED
|
77
|
69
|
|
Overall Study
NOT COMPLETED
|
8
|
6
|
Reasons for withdrawal
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Noncompliance
|
1
|
1
|
|
Overall Study
Inclusion criteria not met
|
1
|
0
|
|
Overall Study
Not treated
|
1
|
0
|
|
Overall Study
Other
|
2
|
1
|
Baseline Characteristics
Efficacy of Inhaled Albuterol Spiromax® in Subjects With Persistent Asthma With Steady State Pharmacokinetics
Baseline characteristics by cohort
| Measure |
Placebo MDPI
n=85 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.7 years
STANDARD_DEVIATION 15.94 • n=5 Participants
|
40.0 years
STANDARD_DEVIATION 18.06 • n=7 Participants
|
38.2 years
STANDARD_DEVIATION 16.99 • n=5 Participants
|
|
Age, Customized
12-17 years
|
17 participants
n=5 Participants
|
14 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Age, Customized
18-64 years
|
67 participants
n=5 Participants
|
58 participants
n=7 Participants
|
125 participants
n=5 Participants
|
|
Age, Customized
65+ years
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
40 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
66 participants
n=5 Participants
|
59 participants
n=7 Participants
|
125 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
17 participants
n=5 Participants
|
11 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Pacific Islander
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
8 participants
n=5 Participants
|
6 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
77 participants
n=5 Participants
|
69 participants
n=7 Participants
|
146 participants
n=5 Participants
|
|
Weight
|
79.8 kg
STANDARD_DEVIATION 22.76 • n=5 Participants
|
79.6 kg
STANDARD_DEVIATION 20.75 • n=7 Participants
|
79.7 kg
STANDARD_DEVIATION 21.77 • n=5 Participants
|
|
Height
|
167.8 cm
STANDARD_DEVIATION 9.23 • n=5 Participants
|
169.8 cm
STANDARD_DEVIATION 10.93 • n=7 Participants
|
168.7 cm
STANDARD_DEVIATION 10.08 • n=5 Participants
|
|
Body Mass Index
|
28.1 kg/m^2
STANDARD_DEVIATION 6.48 • n=5 Participants
|
27.4 kg/m^2
STANDARD_DEVIATION 5.90 • n=7 Participants
|
27.7 kg/m^2
STANDARD_DEVIATION 6.21 • n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1, Day 8 and Day 85Population: Full analysis set included all participants in the intent-to-treat population who received at least 1 dose of study medication and had at least 1 post-baseline assessment.
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Outcome measures
| Measure |
Placebo MDPI
n=84 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period
|
0.38 L*hr
Standard Error 0.114
|
1.30 L*hr
Standard Error 0.120
|
SECONDARY outcome
Timeframe: Day 1Population: Full analysis set
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Outcome measures
| Measure |
Placebo MDPI
n=84 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1
|
0.58 L*hr
Interval 0.24 to 0.92
|
1.63 L*hr
Interval 1.27 to 1.99
|
SECONDARY outcome
Timeframe: Day 8Population: Full analysis set of participants with data at the time point
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Outcome measures
| Measure |
Placebo MDPI
n=83 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=74 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8
|
0.37 L*hr
Interval 0.08 to 0.66
|
1.15 L*hr
Interval 0.84 to 1.45
|
SECONDARY outcome
Timeframe: Day 85Population: Full analysis set of participants with data at the time point
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average over six hours of the FEV1 AUC 0-6 measures adjusted for the baseline measure. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Outcome measures
| Measure |
Placebo MDPI
n=78 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=69 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85
|
0.20 L*hr
Interval -0.05 to 0.44
|
1.12 L*hr
Interval 0.86 to 1.38
|
SECONDARY outcome
Timeframe: Day 1 to Day 93Population: Safety analysis set
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.
Outcome measures
| Measure |
Placebo MDPI
n=84 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Participants With Adverse Events
Any adverse event
|
36 participants
|
22 participants
|
|
Participants With Adverse Events
Severe adverse event
|
3 participants
|
1 participants
|
|
Participants With Adverse Events
Treatment-related adverse event
|
2 participants
|
1 participants
|
|
Participants With Adverse Events
Deaths
|
0 participants
|
0 participants
|
|
Participants With Adverse Events
Other serious adverse event
|
0 participants
|
2 participants
|
|
Participants With Adverse Events
Withdrawn from study due to adverse event
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Day 85Population: Safety population. Only participants with both baseline and endpoint physical examination findings are summarized.
Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint. HEENT = head, eyes, ears, nose, throat.
Outcome measures
| Measure |
Placebo MDPI
n=84 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Skin Abnormal/Abnormal
|
7 participants
|
6 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Musculoskeletal Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Musculoskeletal Abnormal/Abnormal
|
1 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Skin Normal/Normal
|
69 participants
|
63 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Skin Normal/Abnormal
|
5 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Skin Abnormal/Normal
|
2 participants
|
4 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Lymph nodes Normal/Normal
|
83 participants
|
74 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Lymph nodes Normal/Abnormal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Lymph nodes Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Lymph nodes Abnormal/Abnormal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Neurological Normal/Normal
|
83 participants
|
74 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Neurological Normal/Abnormal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Neurological Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Neurological Abnormal/Abnormal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
General appearance Normal/Normal
|
81 participants
|
72 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
General appearance Normal/Abnormal
|
0 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
General appearance Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
General appearance Abnormal/Abnormal
|
2 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
HEENT Normal/Normal
|
59 participants
|
52 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
HEENT Normal/Abnormal
|
1 participants
|
2 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
HEENT Abnormal/Normal
|
7 participants
|
5 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
HEENT Abnormal/Abnormal
|
16 participants
|
15 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Chest and Lungs Normal/Normal
|
76 participants
|
64 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Chest and Lungs Normal/Abnormal
|
2 participants
|
3 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Chest and Lungs Abnormal/Normal
|
3 participants
|
7 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Chest and Lungs Abnormal/Abnormal
|
2 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Heart Normal/Normal
|
82 participants
|
70 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Heart Normal/Abnormal
|
0 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Heart Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Heart Abnormal/Abnormal
|
1 participants
|
3 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Abdomen Normal/Normal
|
82 participants
|
71 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Abdomen Normal/Abnormal
|
0 participants
|
1 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Abdomen Abnormal/Normal
|
0 participants
|
0 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Abdomen Abnormal/Abnormal
|
1 participants
|
2 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Musculoskeletal Normal/Normal
|
81 participants
|
72 participants
|
|
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Musculoskeletal Normal/Abnormal
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Days 8 and 85Population: Safety analysis set
For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: \> 160 beats/minute Diastolic blood pressure: \>100 beats/minute Heart rate: \>120 beats/minute
Outcome measures
| Measure |
Placebo MDPI
n=84 Participants
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=75 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Participants With Clinically Significant Vital Sign Assessments
Systolic blood pressure - high
|
2 participants
|
3 participants
|
|
Participants With Clinically Significant Vital Sign Assessments
Diastolic blood pressure - high
|
2 participants
|
2 participants
|
|
Participants With Clinically Significant Vital Sign Assessments
Heart rate - high
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Maximum Observed Plasma Drug Concentration (Cmax) for Albuterol on Days 1 and 8
Day 1
|
—
|
347.2 pg/mL
Standard Deviation 146.6
|
|
Maximum Observed Plasma Drug Concentration (Cmax) for Albuterol on Days 1 and 8
Day 8
|
—
|
499.1 pg/mL
Standard Deviation 154.3
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Time to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8
Day 1
|
—
|
0.48 hour
Interval 0.18 to 4.95
|
|
Time to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8
Day 8
|
—
|
0.44 hour
Interval 0.25 to 2.02
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min). AUC0-6 on Day 8 is not from pre-dose but at steady state.
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) up to 6 Hours Post-dose (AUC0-6) for Albuterol on Days 1 and 8
Day 1
|
—
|
1325 pg*hr/mL
Standard Deviation 646
|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) up to 6 Hours Post-dose (AUC0-6) for Albuterol on Days 1 and 8
Day 8
|
—
|
2163 pg*hr/mL
Standard Deviation 825
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min). AUC0-t on Day 8 is not from pre-dose but at steady state.
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) for Albuterol on Days 1 and 8
Day 1
|
—
|
1747 pg*hr/mL
Standard Deviation 785
|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) for Albuterol on Days 1 and 8
Day 8
|
—
|
2165 pg*hr/mL
Standard Deviation 839
|
SECONDARY outcome
Timeframe: Day 1Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Infinity Post-dose(AUC0-inf) for Albuterol on Day 1
|
—
|
2278 pg*hr/mL
Standard Deviation 869
|
SECONDARY outcome
Timeframe: Day 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose(AUC0-24) for Albuterol on Day 8
|
—
|
3605 pg*hr/mL
Standard Deviation 1189
|
SECONDARY outcome
Timeframe: Days 1 and 8Population: Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Pharmacokinetic parameters of albuterol were determined on Day 1 after the first dose administration and at steady-state on Day 8. Day 1 serial (10-hr) blood samples for pharmacokinetics pre-dose (within 30 minutes prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5, 6, 8 and 10 hours (±10 minutes). Day 8 serial (6-hr) blood samples for pharmacokinetics pre-dose (within 30 min prior to dosing), and post-dose at the following times: 15 (±5) min, 30 (±5) min, and 1, 2, 3, 4, 5 and 6 hr (±10 min).
Outcome measures
| Measure |
Placebo MDPI
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
Albuterol MDPI
n=16 Participants
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
|---|---|---|
|
Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8
Day 1
|
—
|
4.7 hour
Standard Deviation 1.3
|
|
Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8
Day 8
|
—
|
5.7 hour
Standard Deviation 1.4
|
Adverse Events
Albuterol MDPI
Placebo MDPI
Serious adverse events
| Measure |
Albuterol MDPI
n=75 participants at risk
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
Placebo MDPI
n=84 participants at risk
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Enterocolitis
|
1.3%
1/75 • Number of events 1 • Day 1 to Day 93
|
0.00%
0/84 • Day 1 to Day 93
|
|
Infections and infestations
Pharyngeal abscess
|
1.3%
1/75 • Number of events 1 • Day 1 to Day 93
|
0.00%
0/84 • Day 1 to Day 93
|
Other adverse events
| Measure |
Albuterol MDPI
n=75 participants at risk
Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
|
Placebo MDPI
n=84 participants at risk
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
5.3%
4/75 • Number of events 4 • Day 1 to Day 93
|
3.6%
3/84 • Number of events 3 • Day 1 to Day 93
|
|
Infections and infestations
Upper respiratory tract infection
|
6.7%
5/75 • Number of events 6 • Day 1 to Day 93
|
2.4%
2/84 • Number of events 2 • Day 1 to Day 93
|
|
Nervous system disorders
Headache
|
1.3%
1/75 • Number of events 2 • Day 1 to Day 93
|
6.0%
5/84 • Number of events 6 • Day 1 to Day 93
|
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