COPD Exacerbation
Conditions
Keywords
COPD, chronic obstructive pulmonary disease
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.
Interventions
DRUGFormoterol
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.
OTHERPlacebo
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.
Sponsors
Mylan Specialty L.P.
University of Tennessee Graduate School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 1. A baseline (pre-dose formoterol) FEV1 will be recorded. 2. Subjects will be dosed with formoterol. 3. 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. 4. A percentage of change between the baseline and peak FEV1 will be recorded for this outcome measure. A higher value indicates a better result. |
| 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: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects was dosed with formoterol. 3. 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. |
| 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: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects were dosed with formoterol. 3. 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. |
| 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: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. 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. |
| 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: 1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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 |
| Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol | Measured at visit 1 and again at the end of visit 2 | 1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. A percentage of change between the baseline and peak FVC will be recorded for this outcome measure. |
| 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: 1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. Peak FVC was recorded for this outcome measure and compared amongst groups. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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: 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. | 2 |
| 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: 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. | 5 |
| Total | 7 |
Baseline characteristics
| Characteristic | Total | Formoterol Via DPI Then Formoterol Via Nebulizer | Formoterol Via Nebulizer Then Formoterol Via DPI |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 3 Participants |
| Age, Continuous | 61.0 years STANDARD_DEVIATION 6.9 | 60.5 years STANDARD_DEVIATION 3.6 | 61.2 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 7 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 0 / 6 | 0 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
The Difference Between the Values of Area Under the Response Curve for FEV1
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | The Difference Between the Values of Area Under the Response Curve for FEV1 | 203.0 mcg*hr/mL | Standard Deviation 77.2 |
| Formoterol With Dry Powder Inhaler | The Difference Between the Values of Area Under the Response Curve for FEV1 | 185.0 mcg*hr/mL | Standard Deviation 84 |
Secondary
Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol
Increase in FEV1 from Baseline to 4 hours post dose of formoterol. This will be completed at visit 1 and visit 2. Steps: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects was dosed with formoterol. 3. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol | 12.2 L/sec | Standard Deviation 7.1 |
| Formoterol With Dry Powder Inhaler | Absolute Increase in FEV1 From Baseline After Inhalation of Formoterol | 9.5 L/sec | Standard Deviation 10.4 |
Secondary
Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol
Steps: 1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol | 327.0 mcg*hr/mL | Standard Deviation 75 |
| Formoterol With Dry Powder Inhaler | Area Under the Response Curve for FVC From Baseline Through Four Hours (AUC FVC0-4h) After Inhalation of Formoterol | 293.4 mcg*hr/mL | Standard Deviation 49.8 |
Secondary
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)
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
Population: Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | 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) | -0.59 change in score | Standard Deviation 0.63 |
| Formoterol With Dry Powder Inhaler | 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) | 0 change in score | Standard Deviation 0.5 |
Secondary
Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol
Change in FEV1 from Baseline through 4 hours post formoterol dose. This was completed at visit 1 and visit 2. Steps: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. 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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol | 21.5 percentage change of % predicted FEV1 | Standard Deviation 11.8 |
| Formoterol With Dry Powder Inhaler | Change in FEV1 as a Percentage of Predicted Normal After Inhalation of Formoterol | 18.4 percentage change of % predicted FEV1 | Standard Deviation 14.9 |
Secondary
Peak FEV1 Between the Two Devices (Nebulizer and DPI)
Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: 1. A baseline (pre-dose formoterol) FEV1 was recorded. 2. Subjects were dosed with formoterol. 3. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Peak FEV1 Between the Two Devices (Nebulizer and DPI) | 12.2 L/sec | Standard Deviation 7.1 |
| Formoterol With Dry Powder Inhaler | Peak FEV1 Between the Two Devices (Nebulizer and DPI) | 9.5 L/sec | Standard Deviation 10.4 |
Secondary
Peak FVC Between the Two Devices (Nebulizer and DPI)
Steps: 1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. 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.
Population: Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Peak FVC Between the Two Devices (Nebulizer and DPI) | 86.7 L/sec | Standard Deviation 22 |
| Formoterol With Dry Powder Inhaler | Peak FVC Between the Two Devices (Nebulizer and DPI) | 82.0 L/sec | Standard Deviation 12.6 |
Secondary
Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol
Change in peak FEV1 from Baseline. This will be completed at visit 1 and visit 2. Steps: 1. A baseline (pre-dose formoterol) FEV1 will be recorded. 2. Subjects will be dosed with formoterol. 3. 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. 4. 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol | 28.2 percent change | Standard Deviation 12.3 |
| Formoterol With Dry Powder Inhaler | Percentage Change in Peak FEV1 From Baseline After Inhalation of Formoterol | 21.1 percent change | Standard Deviation 23.4 |
Secondary
Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol
1. A baseline (pre-dose formoterol) FVC was recorded. 2. Subjects were dosed with formoterol. 3. 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. 4. 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
Population: Participants who received a dose of formoterol via nebulizer AND formoterol via dry powder were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formoterol With Nebilizer and Placebo With DPI | Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol | 22.1 percent change | Standard Deviation 11.7 |
| Formoterol With Dry Powder Inhaler | Percentage Change in Peak FVC From Baseline After Inhalation of Formoterol | 18.2 percent change | Standard Deviation 13 |