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

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02126839
• Collaborator: (none)
• Enrollment: 186
• Locations: 52
• Arms: 2
• Duration (Months): 9.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study is to evaluate the chronic-dose efficacy and the safety of Albuterol MDPI compared to placebo in pediatric participants with asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Albuterol MDPI; Drug: Placebo; Drug: ProAir HFA inhaler	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Three-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Chronic-Dose Safety and Efficacy Study of Albuterol Multi-Dose Dry Powder Inhaler (MDPI) Relative to Placebo in Pediatric Asthmatics
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Feb 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: Placebo; Matching Placebo delivered via a multidose dry powder inhaler (MDPI).; Drug: ProAir HFA inhaler; Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.; Other Names: albuterol
Experimental: 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.	Drug: Albuterol MDPI; 90 mcg/actuation of the multidose dry powder inhaler (MDPI).; Other Names: Spiromax® ; Drug: ProAir HFA inhaler; Rescue medication, ProAir hydrofluoroalkane (HFA) inhaler, was dispensed at the run-in visit for the relief of asthma symptoms to be administered as needed.; Other Names: albuterol

Outcome Measures

Primary Outcome Measures

1. 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 [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]

   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).

Secondary Outcome Measures

1. 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 [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]

   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.

2. Summary of Participants With Adverse Events [6 Months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure

2. Male or premenarchal female 4-11 years of age, inclusive, as of the screening visit (SV)

3. Has a documented physician diagnosis of asthma per the EPR-3 Guidelines of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the SV

4. Has the ability to perform spirometry reproducibly consistent with ATS guidelines and protocol-specific guidelines

5. Has FEV1 50-95% predicted for age, height and gender at the SV following a minimum 6-hour period without β2-agonist use. (Note: Predicted values of 49.50-49.99% may be rounded up to 50% and values of 95.01-95.49% may be rounded down to 95%.)

6. Demonstrated reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol. (Note: Reversibility values of 14.50-14.99% may be rounded up to 15%.)

7. Is maintained on low-dose inhaled corticosteroids (ICS, less than or equal to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), or inhaled cromones, and/or on short-acting β2-agonists (SABA); as needed SABA alone is acceptable. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the SV and should be maintained for the duration of the study

8. Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter

9. Can tolerate the withdrawal of applicable medications for qualification at screening

10. Otherwise in general good health, defined as free of any concomitant conditions or treatment that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the trial, and with a clinically acceptable 6-month medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs

11. Parents consenting are capable of understanding the requirements, risks and benefits of study participation, and, as judged by the investigator, capable of giving informed consent and being compliant with all study requirements (eg, visits, record-keeping)

12. The patient is able to correctly use the MDPI device, either alone or with assistance by a parent/guardian.

Exclusion Criteria

1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (eg, lactose, ethanol)

2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the SV or planned participation in another investigational drug trial at any time during this trial

3. History of severe milk protein allergy

4. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza) that has not resolved within 4 weeks preceding the SV

5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A patient must not have had any hospitalization for asthma within 6 months prior to the SV.

6. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the SV must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.

7. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures

8. Use of any prohibited concomitant medications within the washout prescribed per protocol prior to study visits

9. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol as described in the protocol

10. The dosage of any required LTM, ICS, or inhaled cromones, has not been stable for at least 4 weeks. Intranasal corticosteroid and/or cromones have not been stable for at least two weeks prior to the SV. Allowed corticosteroid, LTM, and cromone asthma and allergy medications should be continued at the same doses during the conduct of the study.

11. Presence of any non-asthmatic acute or chronic condition, including but not limited to bronchitis, emphysema, active tuberculosis, bronchiectasis, cystic fibrosis, clinically significant cardiovascular disease (including but not limited to cardiac arrhythmias and uncontrolled hypertension), clinically significant hepatic, renal, or endocrine dysfunction, stroke, uncontrolled diabetes mellitus, hyperthyroidism, convulsive disorder, and malignancy other than basal cell carcinoma. Significant is defined as any condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which could affect the safety or efficacy analyses

12. Any other medical or psychological condition that in the investigator's opinion should preclude study enrollment

13. Previous participation (received MDPI study medication) in an Albuterol MDPI study

14. Study participation by clinical investigator site employees and/or their immediate relatives

15. Study participation by related or non-related individuals living in the same household, ie, only one subject per household may participate in the study at the same time.

16. Require continuous treatment with β-blockers, MAO inhibitors, tricyclic antidepressants, anticholinergics, and/or systemic corticosteroids

17. Treated with oral or injectable corticosteroids within the 6 weeks prior to SV

18. Hospitalization for acute asthma exacerbation >2 times in 12 months prior to screening and/or received emergency room treatment other than nebulized albuterol or been hospitalized for asthma exacerbations within 6 months prior to SV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 12496	Birmingham	Alabama	United States
2	Teva Investigational Site 12500	Mobile	Alabama	United States
3	Teva Investigational Site 12481	Little Rock	Alaska	United States
4	Teva Investigational Site 12515	Anaheim	California	United States
5	Teva Investigational Site 12505	Costa Mesa	California	United States
6	Teva Investigational Site 12476	Huntington Beach	California	United States
7	Teva Investigational Site 12519	Los Angeles	California	United States
8	Teva Investigational Site 12484	Mission Viejo	California	United States
9	Teva Investigational Site 12510	Riverside	California	United States
10	Teva Investigational Site 12483	Rolling Hills Estates	California	United States
11	Teva Investigational Site 12511	Sacramento	California	United States
12	Teva Investigational Site 12485	Stockton	California	United States
13	Teva Investigational Site 12512	Centennial	Colorado	United States
14	Teva Investigational Site 12522	Gainesville	Florida	United States
15	Teva Investigational Site 12535	Hollywood	Florida	United States
16	Teva Investigational Site 12526	Miami	Florida	United States
17	Teva Investigational Site 12516	Orlando	Florida	United States
18	Teva Investigational Site 12517	Tamarac	Florida	United States
19	Teva Investigational Site 12527	Vero Beach	Florida	United States
20	Teva Investigational Site 12513	Winter Park	Florida	United States
21	Teva Investigational Site 12486	Gainesville	Georgia	United States
22	Teva Investigational Site 12497	Lawrenceville	Georgia	United States
23	Teva Investigational Site 12480	Savannah	Georgia	United States
24	Teva Investigational Site 12508	Shiloh	Illinois	United States
25	Teva Investigational Site 12518	Iowa City	Iowa	United States
26	Teva Investigational Site 12523	Covington	Louisiana	United States
27	Teva Investigational Site 12495	Warrensburg	Missouri	United States
28	Teva Investigational Site 12509	Northfield	New Jersey	United States
29	Teva Investigational Site 12524	Brooklyn	New York	United States
30	Teva Investigational Site 12473	Raleigh	North Carolina	United States
31	Teva Investigational Site 12477	Cincinnati	Ohio	United States
32	Teva Investigational Site 12525	Cleveland	Ohio	United States
33	Teva Investigational Site 12502	Middleburg Heights	Ohio	United States
34	Teva Investigational Site 12478	Oklahoma City	Oklahoma	United States
35	Teva Investigational Site 12487	Oklahoma City	Oklahoma	United States
36	Teva Investigational Site 12506	Oklahoma City	Oklahoma	United States
37	Teva Investigational Site 12492	Tulsa	Oklahoma	United States
38	Teva Investigational Site 12507	Gresham	Oregon	United States
39	Teva Investigational Site 12501	Normal	Pennsylvania	United States
40	Teva Investigational Site 12493	Pittsburgh	Pennsylvania	United States
41	Teva Investigational Site 12488	Upland	Pennsylvania	United States
42	Teva Investigational Site 12514	Greenville	South Carolina	United States
43	Teva Investigational Site 12474	Orangeburg	South Carolina	United States
44	Teva Investigational Site 12479	Spartanburg	South Carolina	United States
45	Teva Investigational Site 12489	Boerne	Texas	United States
46	Teva Investigational Site 12475	Waco	Texas	United States
47	Teva Investigational Site 12491	Burke	Virginia	United States
48	Teva Investigational Site 12504	Charlottesville	Virginia	United States
49	Teva Investigational Site 12482	Richmond	Virginia	United States
50	Teva Investigational Site 12498	Richmond	Virginia	United States
51	Teva Investigational Site 12490	Spokane	Washington	United States
52	Teva Investigational Site 12533	Papillion	NE	Thailand

Sponsors and Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Study Director: Sponsor's Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT02126839
• Other Study ID Numbers: ABS-AS-303
• First Posted: Apr 30, 2014
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Asthma; Albuterol

Study Results

Participant Flow

Pre-assignment Detail	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
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

Baseline Characteristics

Arm/Group Title	Placebo MDPI QID	Albuterol MDPI 180 mcg QID	Total
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 Participants	92	94	186
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (1.83)	8.3 (1.69)	8.4 (1.76)
Age, Customized (participants) [Number]
4-7 years	23 25%	30 31.9%	53 28.5%
8-11 years	69 75%	64 68.1%	133 71.5%
Sex: Female, Male (Count of Participants)
Female	37 40.2%	42 44.7%	79 42.5%
Male	55 59.8%	52 55.3%	107 57.5%
Race/Ethnicity, Customized (participants) [Number]
White	41 44.6%	40 42.6%	81 43.5%
Black	48 52.2%	52 55.3%	100 53.8%
American Indian or Alaskan Native	0 0%	1 1.1%	1 0.5%
Pacific Islander	0 0%	1 1.1%	1 0.5%
Other	3 3.3%	0 0%	3 1.6%
Ethnicity (participants) [Number]
Hispanic or Latino	11 12%	14 14.9%	25 13.4%
Not Hispanic or Latino	81 88%	80 85.1%	161 86.6%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	37.2 (13.42)	36.1 (13.46)	36.7 (13.42)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	136.9 (12.67)	135.2 (11.59)	136.0 (12.13)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	19.5 (4.96)	19.4 (5.34)	19.4 (5.14)
Screening FEV1 (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	1.69 (0.44)	1.64 (0.35)	1.66 (0.39)
Screening PPFEV1 (percent of predicted FEV1) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent of predicted FEV1]	87.5 (11.46)	89.0 (12.35)	88.3 (11.91)
Qualifying Airway Reversibility (percentage increase from baseline FEV1) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage increase from baseline FEV1]	22.0 (8.14)	22.9 (8.19)	22.4 (8.16)

Outcome Measures

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
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

Outcome Measure Data

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
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.
Measure Participants	92	92
Least Squares Mean (Standard Error) [% predicted FEV1/hour]	18.71 (3.190)	43.73 (3.200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo MDPI QID, Albuterol MDPI 180 mcg QID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	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

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
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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Placebo MDPI QID	Albuterol MDPI 180 mcg QID
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.
Measure Participants	92	92
Least Squares Mean (Standard Error) [Liters/min*hour]	71.52 (10.201)	147.85 (10.245)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo MDPI QID, Albuterol MDPI 180 mcg QID
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	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

3. Secondary Outcome

Title	Summary of Participants With Adverse Events
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

Outcome Measure Data

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
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.
Measure Participants	92	93
Any adverse event	21 22.8%	21 22.3%
Severe adverse event	0 0%	0 0%
Treatment-related adverse event	0 0%	0 0%
Deaths	0 0%	0 0%
Other serious AE	0 0%	0 0%
Withdrawn from study due to AE	0 0%	0 0%

Adverse Events

Time Frame	Day 1 to Day 22
Arm/Group Title	Placebo MDPI QID		Albuterol MDPI 180 mcg QID
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo MDPI QID		Albuterol MDPI 180 mcg QID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Placebo MDPI QID		Albuterol MDPI 180 mcg QID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/92 (20.7%)		9/93 (9.7%)
Gastrointestinal disorders
Abdominal pain upper	3/92 (3.3%)		0/93 (0%)
Vomiting	0/92 (0%)		3/93 (3.2%)
General disorders
Pyrexia	3/92 (3.3%)		0/93 (0%)
Infections and infestations
Upper respiratory tract infection	3/92 (3.3%)		0/93 (0%)
Injury, poisoning and procedural complications
Ligament sprain	3/92 (3.3%)		0/93 (0%)
Nervous system disorders
Headache	4/92 (4.3%)		3/93 (3.2%)
Respiratory, thoracic and mediastinal disorders
Cough	3/92 (3.3%)		3/93 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.