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A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics

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ClinicalTrials.gov Identifier: NCT02126839
Recruitment Status : Completed
First Posted : April 30, 2014
Results First Posted : February 5, 2016
Last Update Posted : February 5, 2016
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: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Albuterol MDPI
Drug: Placebo
Drug: ProAir HFA inhaler
Enrollment 186
Recruitment Details  
Pre-assignment Details The run-in period (days -14 to Day -1) was conducted in a single blind manner with respect to the Placebo MDPI treatment (2 inhalations QID at approximately 7:00 AM, 12:00 PM, 5:00 PM, and bedtime), so that the patient did not know which treatment was administered.
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID
Hide Arm/Group Description Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks. Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.
Period Title: Overall Study
Started 92 94
Safety Population 92 93
Full Analysis Set 92 92
Completed 82 80
Not Completed 10 14
Reason Not Completed
Adverse Event             0             1
Withdrawal by Subject             1             0
Withdrawal by parent/guardian             1             0
Protocol Violation             2             3
Sponsor request             0             1
Lost to Follow-up             1             4
Not specified             5             5
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID Total
Hide Arm/Group Description Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks. Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks. Total of all reporting groups
Overall Number of Baseline Participants 92 94 186
Hide Baseline Analysis Population Description
Randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 94 participants 186 participants
8.5  (1.83) 8.3  (1.69) 8.4  (1.76)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants 94 participants 186 participants
4-7 years 23 30 53
8-11 years 69 64 133
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 94 participants 186 participants
Female
37
  40.2%
42
  44.7%
79
  42.5%
Male
55
  59.8%
52
  55.3%
107
  57.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants 94 participants 186 participants
White 41 40 81
Black 48 52 100
American Indian or Alaskan Native 0 1 1
Pacific Islander 0 1 1
Other 3 0 3
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 92 participants 94 participants 186 participants
Hispanic or Latino 11 14 25
Not Hispanic or Latino 81 80 161
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 92 participants 94 participants 186 participants
37.2  (13.42) 36.1  (13.46) 36.7  (13.42)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 92 participants 94 participants 186 participants
136.9  (12.67) 135.2  (11.59) 136.0  (12.13)
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 92 participants 94 participants 186 participants
19.5  (4.96) 19.4  (5.34) 19.4  (5.14)
Screening FEV1   [1] 
Mean (Standard Deviation)
Unit of measure:  Liters
Number Analyzed 92 participants 94 participants 186 participants
1.69  (0.44) 1.64  (0.35) 1.66  (0.39)
[1]
Measure Description: FEV1 = forced expiratory volume in 1 second
Screening PPFEV1   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent of predicted FEV1
Number Analyzed 92 participants 94 participants 186 participants
87.5  (11.46) 89.0  (12.35) 88.3  (11.91)
[1]
Measure Description: PPFEV1 = percent-predicted forced expiratory volume in 1 second
Qualifying Airway Reversibility   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage increase from baseline FEV1
Number Analyzed 92 participants 94 participants 186 participants
22.0  (8.14) 22.9  (8.19) 22.4  (8.16)
[1]
Measure Description: For a patient to be eligible for study enrollment, a minimum of 15% increase from the baseline FEV1 must be demonstrated after receiving 180 mcg of albuterol, administered as 2 actuations 1 minute apart.
1.Primary Outcome
Title Baseline Adjusted Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks
Hide Description Following measurement of the baseline FEV1 and dose administration on Days 1 and 22, FEV1 values (highest of 3 acceptable maneuvers) will be obtained at 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±10), 120 (±10), 240 (±10), and 360 (±10) minutes after the completion of dosing. Predicted FEV1 values were computed and adjusted for age, height, and gender according to Eigen et al (Eigen et al 2001) for participants 4 to 5 years of age and to Quanjer et al (Quanjer et al 1995) for participants aged 6 to 11 years using ATS criteria (American Thoracic Society/European Respiratory Society Statement 2007).
Time Frame 30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) includes all participants in the ITT population who receive at least 1 dose of study medication and have at least 1 postbaseline assessment of the primary endpoint.
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID
Hide Arm/Group Description:
Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks.
Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.
Overall Number of Participants Analyzed 92 92
Least Squares Mean (Standard Error)
Unit of Measure: % predicted FEV1/hour
18.71  (3.190) 43.73  (3.200)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI QID, Albuterol MDPI 180 mcg QID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method mixed model repeated measures analysis
Comments Fixed effects of treatment group, treatment day, and study day by treatment interaction, with baseline measured at each study day as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 25.02
Confidence Interval (2-Sided) 95%
16.10 to 33.94
Parameter Dispersion
Type: Standard Error of the mean
Value: 4.52
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Baseline Adjusted Peak Expiratory Flow (PEF) Area Under The Concentration Time Curve Up From Time Zero up to 6 Hours (AUC0-6) Over 3 Weeks
Hide Description Serial PEF measurements were obtained via spirometry. PEF measures for purpose of serial PEF assessment (pre and postdose) were collected from the spirometer assessed PEF, utilizing the values from the efforts selected based on the highest of 3 acceptable FEV1 maneuvers.
Time Frame 30 ±5 and 5 ±2 minutes prior to dosing, and at 5 ±2, 15 ±5, 30 ±5, 45 ±5, 60 ±10, 120 ±10, 240 ±10, and 360 ±10 minutes after completion of dosing on Days 1 and 22
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID
Hide Arm/Group Description:
Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks.
Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.
Overall Number of Participants Analyzed 92 92
Least Squares Mean (Standard Error)
Unit of Measure: Liters/min*hour
71.52  (10.201) 147.85  (10.245)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo MDPI QID, Albuterol MDPI 180 mcg QID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method mixed model repeated measures
Comments Fixed effects of treatment group, treatment day, and study day by treatment interaction, with baseline measured at each study day as a covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 76.33
Confidence Interval (2-Sided) 95%
47.76 to 104.91
Parameter Dispersion
Type: Standard Error of the mean
Value: 14.47
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Summary of 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 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.

Time Frame 6 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis set includes all participants who receive at least 1 dose of study drug. In this population, treatment is assigned based upon the treatment participants actually receive, regardless of the treatment to which they were randomized.
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID
Hide Arm/Group Description:
Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks.
Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.
Overall Number of Participants Analyzed 92 93
Measure Type: Number
Unit of Measure: participants
Any adverse event 21 21
Severe adverse event 0 0
Treatment-related adverse event 0 0
Deaths 0 0
Other serious AE 0 0
Withdrawn from study due to AE 0 0
Time Frame Day 1 to Day 22
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo MDPI QID Albuterol MDPI 180 mcg QID
Hide Arm/Group Description Placebo multidose dry powder inhaler (MDPI) administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 3 weeks. Albuterol multidose dry powder inhaler (MDPI) 90 mcg/inhalation administered as 2 inhalations QID (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for a total daily dose of 720 mcgs for 3 weeks.
All-Cause Mortality
Placebo MDPI QID Albuterol MDPI 180 mcg QID
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo MDPI QID Albuterol MDPI 180 mcg QID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/92 (0.00%)   0/93 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo MDPI QID Albuterol MDPI 180 mcg QID
Affected / at Risk (%) Affected / at Risk (%)
Total   19/92 (20.65%)   9/93 (9.68%) 
Gastrointestinal disorders     
Abdominal pain upper  1  3/92 (3.26%)  0/93 (0.00%) 
Vomiting  1  0/92 (0.00%)  3/93 (3.23%) 
General disorders     
Pyrexia  1  3/92 (3.26%)  0/93 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  3/92 (3.26%)  0/93 (0.00%) 
Injury, poisoning and procedural complications     
Ligament sprain  1  3/92 (3.26%)  0/93 (0.00%) 
Nervous system disorders     
Headache  1  4/92 (4.35%)  3/93 (3.23%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/92 (3.26%)  3/93 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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: 215-591-3000
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT02126839     History of Changes
Other Study ID Numbers: ABS-AS-303
First Submitted: April 28, 2014
First Posted: April 30, 2014
Results First Submitted: January 6, 2016
Results First Posted: February 5, 2016
Last Update Posted: February 5, 2016