Trial Outcomes & Findings for A Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler in Pediatric Asthmatics (NCT NCT02126839)

Last Updated: 2021-11-09

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

186 participants

Primary outcome timeframe

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

Results posted on

2021-11-09

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Placebo MDPI QID 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 MDPI 180 mcg QID 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 Study STARTED	92	94
Overall Study Safety Population	92	93
Overall Study Full Analysis Set	92	92
Overall Study COMPLETED	82	80
Overall Study NOT COMPLETED	10	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo MDPI QID 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 MDPI 180 mcg QID 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 Study Adverse Event	0	1
Overall Study Withdrawal by Subject	1	0
Overall Study Withdrawal by parent/guardian	1	0
Overall Study Protocol Violation	2	3
Overall Study Sponsor request	0	1
Overall Study Lost to Follow-up	1	4
Overall Study Other	5	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo MDPI QID n=92 Participants 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 MDPI 180 mcg QID n=94 Participants 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 n=186 Participants Total of all reporting groups
Age, Continuous	8.5 years STANDARD_DEVIATION 1.83 • n=5 Participants	8.3 years STANDARD_DEVIATION 1.69 • n=7 Participants	8.4 years STANDARD_DEVIATION 1.76 • n=5 Participants
Age, Customized 4-7 years	23 participants n=5 Participants	30 participants n=7 Participants	53 participants n=5 Participants
Age, Customized 8-11 years	69 participants n=5 Participants	64 participants n=7 Participants	133 participants n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants	42 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	52 Participants n=7 Participants	107 Participants n=5 Participants
Race/Ethnicity, Customized White	41 participants n=5 Participants	40 participants n=7 Participants	81 participants n=5 Participants
Race/Ethnicity, Customized Black	48 participants n=5 Participants	52 participants n=7 Participants	100 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	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Ethnicity Hispanic or Latino	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
Ethnicity Not Hispanic or Latino	81 participants n=5 Participants	80 participants n=7 Participants	161 participants n=5 Participants
Weight	37.2 kg STANDARD_DEVIATION 13.42 • n=5 Participants	36.1 kg STANDARD_DEVIATION 13.46 • n=7 Participants	36.7 kg STANDARD_DEVIATION 13.42 • n=5 Participants
Height	136.9 cm STANDARD_DEVIATION 12.67 • n=5 Participants	135.2 cm STANDARD_DEVIATION 11.59 • n=7 Participants	136.0 cm STANDARD_DEVIATION 12.13 • n=5 Participants
Body Mass Index	19.5 kg/m^2 STANDARD_DEVIATION 4.96 • n=5 Participants	19.4 kg/m^2 STANDARD_DEVIATION 5.34 • n=7 Participants	19.4 kg/m^2 STANDARD_DEVIATION 5.14 • n=5 Participants
Screening FEV1	1.69 liters STANDARD_DEVIATION 0.44 • n=5 Participants	1.64 liters STANDARD_DEVIATION 0.35 • n=7 Participants	1.66 liters STANDARD_DEVIATION 0.39 • n=5 Participants
Screening PPFEV1	87.5 percent of predicted FEV1 STANDARD_DEVIATION 11.46 • n=5 Participants	89.0 percent of predicted FEV1 STANDARD_DEVIATION 12.35 • n=7 Participants	88.3 percent of predicted FEV1 STANDARD_DEVIATION 11.91 • n=5 Participants
Qualifying Airway Reversibility	22.0 percentage increase from baseline FEV1 STANDARD_DEVIATION 8.14 • n=5 Participants	22.9 percentage increase from baseline FEV1 STANDARD_DEVIATION 8.19 • n=7 Participants	22.4 percentage increase from baseline FEV1 STANDARD_DEVIATION 8.16 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo MDPI QID n=92 Participants 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 MDPI 180 mcg QID n=92 Participants 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.
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	18.71 % predicted FEV1/hour Standard Error 3.190	43.73 % predicted FEV1/hour Standard Error 3.200

SECONDARY outcome

Timeframe: 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

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo MDPI QID n=92 Participants 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 MDPI 180 mcg QID n=92 Participants 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.
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	71.52 Liters/min*hour Standard Error 10.201	147.85 Liters/min*hour Standard Error 10.245

SECONDARY outcome

Timeframe: 6 Months

Population: 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.

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

Outcome measures
Measure	Placebo MDPI QID n=92 Participants 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 MDPI 180 mcg QID n=93 Participants 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.
Summary of Participants With Adverse Events Any adverse event	21 participants	21 participants
Summary of Participants With Adverse Events Severe adverse event	0 participants	0 participants
Summary of Participants With Adverse Events Treatment-related adverse event	0 participants	0 participants
Summary of Participants With Adverse Events Deaths	0 participants	0 participants
Summary of Participants With Adverse Events Other serious AE	0 participants	0 participants
Summary of Participants With Adverse Events Withdrawn from study due to AE	0 participants	0 participants

Adverse Events

Placebo MDPI QID

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Albuterol MDPI 180 mcg QID

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo MDPI QID n=92 participants at risk 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 MDPI 180 mcg QID n=93 participants at risk 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.
Gastrointestinal disorders Abdominal pain upper	3.3% 3/92 • Day 1 to Day 22	0.00% 0/93 • Day 1 to Day 22
Gastrointestinal disorders Vomiting	0.00% 0/92 • Day 1 to Day 22	3.2% 3/93 • Day 1 to Day 22
General disorders Pyrexia	3.3% 3/92 • Day 1 to Day 22	0.00% 0/93 • Day 1 to Day 22
Infections and infestations Upper respiratory tract infection	3.3% 3/92 • Day 1 to Day 22	0.00% 0/93 • Day 1 to Day 22
Injury, poisoning and procedural complications Ligament sprain	3.3% 3/92 • Day 1 to Day 22	0.00% 0/93 • Day 1 to Day 22
Nervous system disorders Headache	4.3% 4/92 • Day 1 to Day 22	3.2% 3/93 • Day 1 to Day 22
Respiratory, thoracic and mediastinal disorders Cough	3.3% 3/92 • Day 1 to Day 22	3.2% 3/93 • Day 1 to Day 22

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc

Phone: 215-591-3000

Email: [email protected]

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