COPD Aerosol Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers

• Sponsor: University of Tennessee Graduate School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT02291016
• Collaborator: Mylan Specialty L.P. (Other)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 12.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to compare drug delivery and lung function after treatment with formoterol from a nebulizer versus a dry powder inhaler (DPI) in patients recovering from severe exacerbations of COPD. This is to determine if one device is superior in providing better lung function and drug deposition in this clinical setting.

Condition or Disease	Intervention/Treatment	Phase
COPD Exacerbation	Drug: Formoterol; Other: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Dummy, Crossover, Single-Center Study Comparing the Efficacy of Nebulizers Versus Dry Powder Inhalers in the Treatment of Patients Recovering From Severe Exacerbations of Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Formoterol via DPI then Formoterol via nebulizer Group A: Received Formoterol 12 µg via DPI and placebo via nebulizer at treatment visit #1, and Formoterol 20 µg (solution form) via nebulizer and placebo via DPI at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Drug: Formoterol; Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Foradil PERFOROMIST ; Other: Placebo; Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Normal Saline
Active Comparator: Formoterol via nebulizer then Formoterol via DPI Group B: Received Formoterol 20 µg (solution form) via nebulizer and placebo via a DPI at treatment visit #1, and Formoterol 12 µg via a DPI with placebo via nebulizer at treatment visit 2. Placebo: The placebo used will be sterile, preservative free, normal saline for nebulizer inhalation and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Drug: Formoterol; Comparison of dosage administered via a nebulizer versus dosage administered via a dry powder inhaler. 12 µg Formoterol with the dry powder inhaler and 20 µg (solution form) of Formoterol with the nebulizer. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Foradil PERFOROMIST ; Other: Placebo; Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.; Other Names: Normal Saline

Outcome Measures

Primary Outcome Measures

1. The Difference Between the Values of Area Under the Response Curve for FEV1 [Baseline through study completion (visit 1 through visit 2)]

   The difference between the values of area under the response curve for FEV1 from baseline through four hours (AUC FEV1 0-4h) after inhalation of formoterol with a nebulizer or a dry powder inhaler.

Secondary Outcome Measures

1. Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol [From pre-dose formoterol (baseline 0hrs) to 30 minutes, 1,2, and 4 hours post dose at visit 1 and measured again at visit 2]

   Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 will be recorded. Subjects will be dosed with formoterol. Serial FEV1 assessments will completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement can be recorded. A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result.

2. Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol [Measured at visit 1 and visit 2 after dosing and all FEV1 testing has been completed]

   Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects was dosed with formoterol. Serial FEV1 assessments were completed, and recorded at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so serial FEV1 measurements could be recorded.

3. Peak FEV1 Between the Two Devices (Nebulizer and DPI) [Measured from Start of visit 1 until the completion of visit 2]

   Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement could recorded. 5. Peak measurements from visit 1 and visit 2 will be compared for any significant change in FEV1 values.

4. Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol [Baseline through study completion (visit 1 through visit 2)]

   Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FEV1 values were recorded. A percentage of change from baseline FEV1 to each serial measurement of FEV1 was collected. The % of change at each time point was then used to get a measure of overall percentage change of the predicted FEV1 value.

5. Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol [Measured at visit 1 and again at the end of visit 2]

   Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Data was all time points were used to obtain the total area under the curve

6. Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol [Measured at visit 1 and again at the end of visit 2]

   A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. A percentage of change between the baseline and peak FVC will be recorded for this outcome measure.

7. Peak FVC Between the Two Devices (Nebulizer and DPI) [Peak FVC at visit 1 will be compared to the peak FVC at visit 2 for any significant change.]

   Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Peak FVC was recorded for this outcome measure and compared amongst groups.

8. Change in Dyspnea Based on the Borg Dyspnea Scale for Shortness of Breath (Pre-dose Administration and 60 Minutes After Inhalation of Formoterol With a Nebulizer or a DPI) [Measured at visit 1 and again at the end of visit 2]

   The Shortness of Breath Modified Borg Dyspnea Scale The scale goes from 0-10, zero meaning no difficulty breathing and ten meaning maximal difficulty. A decrease of score indicates an improvement. Patients were asked to complete the scale pre-dose and again one hour post formoterol dose. This was completed at both visit 1 and visit 2. The value recorded was the difference between the baseline value and the post 60 minute value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current or past cigarette smoking history of >/= 10 pack-years.

• FEV1/FVC ratio </= 70%.

• Known diagnosis of COPD.

• Current hospitalization for a primary diagnosis of acute exacerbation of COPD.

• Must be able to understand and willing to sign an informed consent document.

Exclusion Criteria:

• On a ventilator or mask ventilation.

• Allergy or contraindication to Formoterol use.

• Marked QTc prolongation (> 450 ms).

• Liver cirrhosis or chronic renal insufficiency (serum creatinine > 2 mg/dL).

• Atrial fibrillation with rapid ventricular response (heart rate > 110 bpm) or ventricular arrhythmia (frequent PVCs, ventricular tachycardia).

• Acute myocardial infarction within 12 weeks of patient study registration.

• Known pulmonary embolism.

• Known or suspected lung cancer.

• Known neuromuscular disease, stroke with residual hemiparesis, or untreated Parkinsonism

• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or sub dermal implants).

• Inability to understand instructions.

• Participation in another investigational drug clinical trial within 30 days of patient study registration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920

Sponsors and Collaborators

• University of Tennessee Graduate School of Medicine
• Mylan Specialty L.P.

Investigators

• Principal Investigator: Rajiv Dhand, MD, University of Tennessee Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rajiv Dhand, MD, Principal Investigator, University of Tennessee Graduate School of Medicine
• ClinicalTrials.gov Identifier: NCT02291016
• Other Study ID Numbers: 3798
• First Posted: Nov 14, 2014
• Last Update Posted: Mar 19, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Rajiv Dhand, MD, Principal Investigator, University of Tennessee Graduate School of Medicine: COPD; chronic obstructive pulmonary disease
• Additional relevant MeSH terms: Formoterol Fumarate

Study Results

Participant Flow

Arm/Group Title	Formoterol Via DPI Then Formoterol Via Nebulizer	Formoterol Via Nebulizer Then Formoterol Via DPI
Arm/Group Description	Group A: Received Formoterol 12 µg via DPI and placebo via nebulizer at treatment visit #1, and then Formoterol 20 µg (solution form) via nebulizer and placebo via DPI at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Group B: Received Formoterol 20 µg (solution form) via nebulizer and placebo via a DPI at treatment visit #1, and then Formoterol 12 µg via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Period Title: Visit 1
STARTED	2	5
COMPLETED	2	5
NOT COMPLETED	0	0
Period Title: Visit 1
STARTED	2	5
COMPLETED	1	5
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Formoterol Via DPI Then Formoterol Via Nebulizer	Formoterol Via Nebulizer Then Formoterol Via DPI	Total
Arm/Group Description	Group A: Received Formoterol 12 µg via DPI and placebo via nebulizer at treatment visit #1, and Formoterol 20 µg (solution form) via nebulizer and placebo via DPI at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Group B: Received Formoterol 20 µg (solution form) via nebulizer and placebo via a DPI at treatment visit #1, and Formoterol 12 µg via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Total of all reporting groups
Overall Participants	2	5	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	3 60%	5 71.4%
>=65 years	0 0%	2 40%	2 28.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.5 (3.6)	61.2 (8.3)	61.0 (6.9)
Sex: Female, Male (Count of Participants)
Female	1 50%	4 80%	5 71.4%
Male	1 50%	1 20%	2 28.6%
Region of Enrollment (Count of Participants)
United States	2 100%	5 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	The Difference Between the Values of Area Under the Response Curve for FEV1
Description	The difference between the values of area under the response curve for FEV1 from baseline through four hours (AUC FEV1 0-4h) after inhalation of formoterol with a nebulizer or a dry powder inhaler.
Time Frame	Baseline through study completion (visit 1 through visit 2)

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included. One patient did not complete the full study, which is why only 6 participants who took formoterol with Nebulizer were analyzed. Collected at baseline, visit 1, and visit 2 at pre-dose then 30 minutes,1hr, 2hr, and 4hr post-dose

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [mcg*hr/mL]	203.0 (77.2)	185.0 (84.0)

2. Secondary Outcome

Title	Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol
Description	Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 will be recorded. Subjects will be dosed with formoterol. Serial FEV1 assessments will completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement can be recorded. A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result.
Time Frame	From pre-dose formoterol (baseline 0hrs) to 30 minutes, 1,2, and 4 hours post dose at visit 1 and measured again at visit 2

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included. One patient did not complete the full study, which is why only 6 participants who took formoterol with Nebulizer were analyzed.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [percent change]	28.2 (12.3)	21.1 (23.4)

3. Secondary Outcome

Title	Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol
Description	Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects was dosed with formoterol. Serial FEV1 assessments were completed, and recorded at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so serial FEV1 measurements could be recorded.
Time Frame	Measured at visit 1 and visit 2 after dosing and all FEV1 testing has been completed

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.One patient did not complete the full study, which is why only 6 participants who took formoterol with Nebulizer were analyzed.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [L/sec]	12.2 (7.1)	9.5 (10.4)

4. Secondary Outcome

Title	Peak FEV1 Between the Two Devices (Nebulizer and DPI)
Description	Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol so a peak measurement could recorded. 5. Peak measurements from visit 1 and visit 2 will be compared for any significant change in FEV1 values.
Time Frame	Measured from Start of visit 1 until the completion of visit 2

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included. One patient did not complete the full study, which is why only 6 participants who took formoterol with Nebulizer were analyzed.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [L/sec]	12.2 (7.1)	9.5 (10.4)

5. Secondary Outcome

Title	Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol
Description	Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2. Steps: A baseline (pre-dose formoterol) FEV1 was recorded. Subjects were dosed with formoterol. Serial FEV1 assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FEV1 values were recorded. A percentage of change from baseline FEV1 to each serial measurement of FEV1 was collected. The % of change at each time point was then used to get a measure of overall percentage change of the predicted FEV1 value.
Time Frame	Baseline through study completion (visit 1 through visit 2)

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included. One patient did not complete the full study, which is why only 6 participants who took formoterol with Nebulizer were analyzed.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [percentage change of % predicted FEV1]	21.5 (11.8)	18.4 (14.9)

6. Secondary Outcome

Title	Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol
Description	Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Data was all time points were used to obtain the total area under the curve
Time Frame	Measured at visit 1 and again at the end of visit 2

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.One patient did not complete the full study, which is why only 6 participants who took formoterol with nebulizer were analyzed.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [mcg*hr/mL]	327.0 (75.0)	293.4 (49.8)

7. Secondary Outcome

Title	Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol
Description	A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. A percentage of change between the baseline and peak FVC will be recorded for this outcome measure.
Time Frame	Measured at visit 1 and again at the end of visit 2

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [percent change]	22.1 (11.7)	18.2 (13.0)

8. Secondary Outcome

Title	Peak FVC Between the Two Devices (Nebulizer and DPI)
Description	Steps: A baseline (pre-dose formoterol) FVC was recorded. Subjects were dosed with formoterol. Serial FVC assessments were completed at 15 minutes, 30 minutes, 1 hour, 2 hour, and 4 hour post dose of formoterol and serial FVC values were recorded. Peak FVC was recorded for this outcome measure and compared amongst groups.
Time Frame	Peak FVC at visit 1 will be compared to the peak FVC at visit 2 for any significant change.

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [L/sec]	86.7 (22.0)	82.0 (12.6)

9. Secondary Outcome

Title	Change in Dyspnea Based on the Borg Dyspnea Scale for Shortness of Breath (Pre-dose Administration and 60 Minutes After Inhalation of Formoterol With a Nebulizer or a DPI)
Description	The Shortness of Breath Modified Borg Dyspnea Scale The scale goes from 0-10, zero meaning no difficulty breathing and ten meaning maximal difficulty. A decrease of score indicates an improvement. Patients were asked to complete the scale pre-dose and again one hour post formoterol dose. This was completed at both visit 1 and visit 2. The value recorded was the difference between the baseline value and the post 60 minute value.
Time Frame	Measured at visit 1 and again at the end of visit 2

Outcome Measure Data

Analysis Population Description

Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.

Arm/Group Title	Formoterol With Nebilizer and Placebo With DPI	Formoterol With Dry Powder Inhaler and Placebo With Nebulizer
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.	Formoterol: One dosing of 12 µg via dry powder inhaler at either visit 1 or visit 2 depending on randomization assignment, which is detailed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
Measure Participants	6	7
Mean (Standard Deviation) [change in score]	-0.59 (0.63)	0 (.50)

Adverse Events

Time Frame	Collected from subject randomization through subject study completion (visit 1-visit 2), which was approximately 9 days total.
Adverse Event Reporting Description	Instead of reporting the findings from Group A ( Dosed with Nebulizer placebo and DPI formoterol at visit 1, and dosed with nebulizer formoterol and DPI placebo at visit 2), and Group B (Dosed with nebulizer formoterol and DPI placebo at visit 1 , and dosed with nebulizer placebo and DPI formoterol at visit 2), we reported the adverse event groups by the following: Formoterol via Nebulizer and Formoterol via DPI, as patients were given both in this cross-over study.
Arm/Group Title	Formoterol With Nebulizer		Formoterol With Dry Powder Inhaler
Arm/Group Description	One dose of Formoterol 20 µg (solution form) via nebulizer at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.		One dose of Formoterol 12 µg (solution form) via DPI at either visit 1 or visit 2 depending on group randomization, which is listed below. Randomization: Group A: Received formoterol via DPI and placebo via nebulizer at treatment visit #1, and formoterol via nebulizer and placebo via DPI at treatment visit 2. Group B: Received formoterol via nebulizer and placebo via a DPI at treatment visit #1, and formoterol via a DPI with placebo via nebulizer at treatment visit 2. Placebo: Comparison of drug administered via a nebulizer versus a dry powder inhaler. The placebo used will be sterile, preservative free, normal saline for inhalation for the nebulizer and a matched capsule without active drug for the dry powder inhaler. All patients will receive 2 ml of normal saline with the nebulizer to match the volume of nebulized formoterol solution. Patients will receive formoterol and placebo at both study visit #1 and visit #2.
All Cause Mortality
	Formoterol With Nebulizer		Formoterol With Dry Powder Inhaler
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)
Serious Adverse Events
	Formoterol With Nebulizer		Formoterol With Dry Powder Inhaler
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Formoterol With Nebulizer		Formoterol With Dry Powder Inhaler
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.