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Efficacy of Inhaled Albuterol Spiromax® in Subjects With Persistent Asthma With Steady State Pharmacokinetics

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ClinicalTrials.gov Identifier: NCT01747629
Recruitment Status : Completed
First Posted : December 11, 2012
Results First Posted : May 21, 2015
Last Update Posted : June 26, 2015
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Placebo MDPI
Drug: Albuterol MDPI
Enrollment 160
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks. 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.
Period Title: Overall Study
Started 85 75
Treated 84 [1] 75 [1]
Completed 77 69
Not Completed 8 6
Reason Not Completed
Adverse Event             1             2
Withdrawal by Subject             2             2
Noncompliance             1             1
Inclusion criteria not met             1             0
Not treated             1             0
Not specified             2             1
[1]
Safety set and full analysis set
Arm/Group Title Placebo MDPI Albuterol MDPI Total
Hide Arm/Group Description Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks. 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 of all reporting groups
Overall Number of Baseline Participants 85 75 160
Hide Baseline Analysis Population Description
Randomized analysis set
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 75 participants 160 participants
36.7  (15.94) 40.0  (18.06) 38.2  (16.99)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 75 participants 160 participants
12-17 years 17 14 31
18-64 years 67 58 125
65+ years 1 3 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 75 participants 160 participants
Female
45
  52.9%
36
  48.0%
81
  50.6%
Male
40
  47.1%
39
  52.0%
79
  49.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 75 participants 160 participants
White 66 59 125
Black 17 11 28
Asian 1 0 1
American Indian or Alaskan Native 0 1 1
Pacific Islander 0 1 1
Other 1 3 4
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 85 participants 75 participants 160 participants
Hispanic or Latino 8 6 14
Not Hispanic or Latino 77 69 146
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 85 participants 75 participants 160 participants
79.8  (22.76) 79.6  (20.75) 79.7  (21.77)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 85 participants 75 participants 160 participants
167.8  (9.23) 169.8  (10.93) 168.7  (10.08)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 85 participants 75 participants 160 participants
28.1  (6.48) 27.4  (5.90) 27.7  (6.21)
1.Primary Outcome
Title Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period
Hide Description

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.

Time Frame Day 1, Day 8 and Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 84 75
Mean (Standard Error)
Unit of Measure: L*hr
0.38  (0.114) 1.30  (0.120)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Albuterol MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance at the 0.05 level.
Method mixed-model repeated-measures (MMRM)
Comments Fixed effects- pooled center, treatment group, study day, and study day by drug interaction, with baseline measured at each study day as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.59 to 1.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.163
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 84 75
Mean (95% Confidence Interval)
Unit of Measure: L*hr
0.58
(0.24 to 0.92)
1.63
(1.27 to 1.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Albuterol MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To adjust for multiplicity, so that the overall alpha level for all tests was controlled at the 0.05 level, tests were done sequentially [day 1, then day 8, then day 85] and terminated if individual results were not significant at the 0.05 level.
Method mixed model repeated measures (MMRM)
Comments Fixed effects- pooled center, treatment group, study day, and study day by drug interaction, with baseline measured at each study day as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.56 to 1.55
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.249
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8
Hide Description

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.

Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set of participants with data at the time point
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 83 74
Mean (95% Confidence Interval)
Unit of Measure: L*hr
0.37
(0.08 to 0.66)
1.15
(0.84 to 1.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Albuterol MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments To adjust for multiplicity, so that the overall alpha level for all tests was controlled at the 0.05 level, tests were done sequentially [day 1, then day 8, then day 85] and terminated if individual results were not significant at the 0.05 level.
Method mixed model repeated measures (MMRM)
Comments Fixed effects- pooled center, treatment group, study day, and study day by drug interaction, with baseline measured at each study day as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.35 to 1.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.212
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85
Hide Description

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.

Time Frame Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set of participants with data at the time point
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 78 69
Mean (95% Confidence Interval)
Unit of Measure: L*hr
0.20
(-0.05 to 0.44)
1.12
(0.86 to 1.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI, Albuterol MDPI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments To adjust for multiplicity, so that the overall alpha level for all tests was controlled at the 0.05 level, tests were done sequentially [day 1, then day 8, then day 85] and terminated if individual results were not significant at the 0.05 level.
Method mixed model repeated measures (MMRM)
Comments Fixed effects- pooled center, treatment group, study day, and study day by drug interaction, with baseline measured at each study day as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.57 to 1.28
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.180
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Participants With Adverse Events
Hide Description Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Time Frame Day 1 to Day 93
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 84 75
Measure Type: Number
Unit of Measure: participants
Any adverse event 36 22
Severe adverse event 3 1
Treatment-related adverse event 2 1
Deaths 0 0
Other serious adverse event 0 2
Withdrawn from study due to adverse event 1 2
6.Secondary Outcome
Title Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Hide Description 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.
Time Frame Day 1 (Baseline), Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only participants with both baseline and endpoint physical examination findings are summarized.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 84 75
Measure Type: Number
Unit of Measure: participants
General appearance Normal/Normal 81 72
General appearance Normal/Abnormal 0 1
General appearance Abnormal/Normal 0 0
General appearance Abnormal/Abnormal 2 1
HEENT Normal/Normal 59 52
HEENT Normal/Abnormal 1 2
HEENT Abnormal/Normal 7 5
HEENT Abnormal/Abnormal 16 15
Chest and Lungs Normal/Normal 76 64
Chest and Lungs Normal/Abnormal 2 3
Chest and Lungs Abnormal/Normal 3 7
Chest and Lungs Abnormal/Abnormal 2 0
Heart Normal/Normal 82 70
Heart Normal/Abnormal 0 1
Heart Abnormal/Normal 0 0
Heart Abnormal/Abnormal 1 3
Abdomen Normal/Normal 82 71
Abdomen Normal/Abnormal 0 1
Abdomen Abnormal/Normal 0 0
Abdomen Abnormal/Abnormal 1 2
Musculoskeletal Normal/Normal 81 72
Musculoskeletal Normal/Abnormal 1 1
Musculoskeletal Abnormal/Normal 0 0
Musculoskeletal Abnormal/Abnormal 1 1
Skin Normal/Normal 69 63
Skin Normal/Abnormal 5 1
Skin Abnormal/Normal 2 4
Skin Abnormal/Abnormal 7 6
Lymph nodes Normal/Normal 83 74
Lymph nodes Normal/Abnormal 0 0
Lymph nodes Abnormal/Normal 0 0
Lymph nodes Abnormal/Abnormal 0 0
Neurological Normal/Normal 83 74
Neurological Normal/Abnormal 0 0
Neurological Abnormal/Normal 0 0
Neurological Abnormal/Abnormal 0 0
7.Secondary Outcome
Title Participants With Clinically Significant Vital Sign Assessments
Hide Description

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

Time Frame Days 8 and 85
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 84 75
Measure Type: Number
Unit of Measure: participants
Systolic blood pressure - high 2 3
Diastolic blood pressure - high 2 2
Heart rate - high 0 0
8.Secondary Outcome
Title Maximum Observed Plasma Drug Concentration (Cmax) for Albuterol on Days 1 and 8
Hide Description 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).
Time Frame Days 1 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: pg/mL
Day 1 347.2  (146.6)
Day 8 499.1  (154.3)
9.Secondary Outcome
Title Time to Observed Peak Plasma Concentration (Tmax) for Albuterol on Days 1 and 8
Hide Description 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).
Time Frame Days 1 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Median (Full Range)
Unit of Measure: hour
Day 1
0.48
(0.18 to 4.95)
Day 8
0.44
(0.25 to 2.02)
10.Secondary Outcome
Title 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
Hide Description

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.

Time Frame Days 1 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
Day 1 1325  (646)
Day 8 2163  (825)
11.Secondary Outcome
Title 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
Hide Description

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.

Time Frame Days 1 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
Day 1 1747  (785)
Day 8 2165  (839)
12.Secondary Outcome
Title Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Infinity Post-dose(AUC0-inf) for Albuterol on Day 1
Hide Description 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).
Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
2278  (869)
13.Secondary Outcome
Title Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose(AUC0-24) for Albuterol on Day 8
Hide Description 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).
Time Frame Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
3605  (1189)
14.Secondary Outcome
Title Terminal Plasma Half-life (t1/2) for Albuterol on Days 1 and 8
Hide Description 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).
Time Frame Days 1 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set representing a subset of participants from the Albuterol MDPI treatment arm.
Arm/Group Title Placebo MDPI Albuterol MDPI
Hide Arm/Group Description:
Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
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 Number of Participants Analyzed 0 16
Mean (Standard Deviation)
Unit of Measure: hour
Day 1 4.7  (1.3)
Day 8 5.7  (1.4)
Time Frame Day 1 to Day 93
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Albuterol MDPI Placebo MDPI
Hide Arm/Group Description 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 multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
All-Cause Mortality
Albuterol MDPI Placebo MDPI
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Albuterol MDPI Placebo MDPI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/75 (2.67%)      0/84 (0.00%)    
Gastrointestinal disorders     
Enterocolitis  1  1/75 (1.33%)  1 0/84 (0.00%)  0
Infections and infestations     
Pharyngeal abscess  1  1/75 (1.33%)  1 0/84 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Albuterol MDPI Placebo MDPI
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/75 (12.00%)      10/84 (11.90%)    
Infections and infestations     
Nasopharyngitis  1  4/75 (5.33%)  4 3/84 (3.57%)  3
Upper respiratory tract infection  1  5/75 (6.67%)  6 2/84 (2.38%)  2
Nervous system disorders     
Headache  1  1/75 (1.33%)  2 5/84 (5.95%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 1-215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01747629     History of Changes
Other Study ID Numbers: ABS-AS-304
First Submitted: December 7, 2012
First Posted: December 11, 2012
Results First Submitted: May 2, 2015
Results First Posted: May 21, 2015
Last Update Posted: June 26, 2015