Asthma
Conditions
Keywords
allergen challenge, early asthmatic response, mild asthma, late asthmatic response
Brief summary
We propose to use an inhaled allergen challenge model to explore the individual contributions of the components of a novel long-acting beta agonist/ inhaled corticosteroid combination product and its components on protection from allergic triggers in asthma
Detailed description
Asthma is an increasingly common disease and is essentially caused by an allergic type of reaction of the immune system. Airways of the lungs become inflamed and narrow as a result of a reaction to triggers like chemicals (house-hold cleaning products, pollution) and allergens (house dust mite and cat or dog fur). The airways become blocked, causing shortness of breath and wheezing. The purpose of this study is to find out more information about how effective the study drugs are at protecting the lungs against allergic triggers of asthma. There are three study drugs being investigated in this study: fluticasone furoate on its own, GW642444M on its own and a combination of fluticasone furoate (FF) and GW642444M. FF is a corticosteroid that is being developed by for the treatment of asthma. A nasal spray formulation of FF has been approved for marketing in the USA, Europe and Japan for the treatment of hayfever (rhinitis) but the dry powder formulation used in this study is not yet approved. GW642444M is a long-acting beta2-agonist being developed by GSK for the treatment of chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. The combination of FF/GW642444M is being developed as a once-daily treatment for both asthma and COPD. Study treatment will be taken for 21 days in each period (4 treatment periods: FF alone, GW642444M alone, FF/GW64244M combination and placebo) and each subject will receive all treatments. On D21 subjects will undergo an allergen challenge, followed by a methacholine challenge on D22. The washout between treatment periods will be 21-35 days.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2). * Females of non-child bearing potential. * Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation * Pre-bronchodilator FEV1 \>70% of predicted at screening * Subjects who are current non-smokers * Methacholine challenge PC20 \< 8 mg/mL at screening * Screening allergen challenge demonstrates that the subject experiences an early asthmatic response
Exclusion criteria
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities * Subject is hypertensive at screening * Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. * History of life-threatening asthma * Symptomatic with hay fever at screening or predicted to have symptomatic hayfever * Unable to abstain from short acting beta agonists * Unable to abstain from antihistamines * Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-asthma anti-rhinitis or hay fever medication * The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months * undergoing allergen desensitisation therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | Day 21 of each treatment period (up to Study Day 197) | Forced expiratory volume in one second (FEV1) is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen (administered by inhalation) 1 hr after dosing on Day 21. Minimum FEV1 over 4-10 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 4 and 10 hrs post-allergen challenge, inclusive of the 4 hr and 10 hr timepoints (i.e., minimum over 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs). Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines. |
| LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | Day 21 of each treatment period (up to Study Day 197) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hour after dosing on Day 21. LAR FEV1 was measured 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs post-allergen challenge on Day 21. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines. |
| Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | Day 21 of each treatment period (up to Study Day 197) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. Minimum FEV1 over 0-2 hrs post-allergen challenge (Minimum EAR) is the minimum value of all of the post-allergen challenge timepoints up to and including 2 hours post-allergen challenge (i.e., minimum over 5 minutes (min), 10 min, 15 min, 20 min, 30 min, 45 min and 1 hr, 1.5 hrs, and 2 hrs. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines. |
| EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | Day 21 of each treatment period (up to Study Day 197) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. The EAR FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Least squares means were obtained by adjusting for period and participant and period Baselines. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | Day 21 of each treatment period (up to Study Day 197) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Maximum percent change was calculated as the minimum FEV1 minus the saline FEV1 value divided by the saline FEV1 multiplied by 100. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline FEV1 value. |
| Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period | Day 22 of each treatment period (up to Study Day 198) | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants inhaled doubling increments of methacholine until a \>=20% fall in FEV1 from the saline value was achieved. After inhalation of saline, 3 measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. |
Countries
Australia, New Zealand, Sweden
Participant flow
Pre-assignment details
Participants meeting all of the inclusion criteria and none of the exclusion criteria during the Screening Visit, conducted 14-42 days prior to the first dose of study medication, entered a 14-day Run-in Period. Participants were then randomized to 4 Treatment Periods, each lasting 21 days and separated by a nominal washout period of 21-35 days.
Participants by arm
| Arm | Count |
|---|---|
| Placebo, FF/VI 100/25 µg OD, FF 100 µg OD, VI 25 µg All participants received one of the following four treatments in one of four treatment periods once daily (OD) from the Dry Powder Inhaler (DPI) for 21 days: Placebo; Fluticasone Furoate /Vilanterol (FF/VI) 100/25 microgram (µg) dry inhalation powder; Fluticasone Furoate (FF) 100 µg dry inhalation powder; and Vilanterol (VI) 25 µg dry inhalation powder. Participants were randomized to receive treatment in one of the four following sequences: (1) VI 25 µg, Placebo, FF 100 µg, FF/VI 100/25 µg; (2) FF/VI 100/25 µg, FF 100 µg, Placebo, VI 25 µg; (3) Placebo, FF/VI 100/25 µg, VI 25 µg, FF 100 µg; (4) FF 100 µg, VI 25 µg, FF/VI 100/25 µg, Placebo. The four treatment periods were separated by a washout period of 21 to 35 days. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 3 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo, FF/VI 100/25 µg OD, FF 100 µg OD, VI 25 µg |
|---|---|
| Age, Continuous | 30.8 Years STANDARD_DEVIATION 7.46 |
| Gender Female | 8 Participants |
| Gender Male | 19 Participants |
| Race/Ethnicity, Customized East Asian Heritage | 1 participants |
| Race/Ethnicity, Customized Mixed Race | 1 participants |
| Race/Ethnicity, Customized White/Caucasian/European Heritage | 25 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 27 | 20 / 27 | 19 / 27 | 22 / 26 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 27 | 0 / 26 |
Outcome results
Primary
EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. The EAR FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Least squares means were obtained by adjusting for period and participant and period Baselines. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value.
Time frame: Day 21 of each treatment period (up to Study Day 197)
Population: Efficacy Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.560 Liters |
| FF/VI 100/25 µg OD | EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.297 Liters |
| FF 100 µg OD | EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.386 Liters |
| VI 25 µg OD | EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.533 Liters |
95% CI: [-0.037, 0.215]
95% CI: [0.101, 0.371]
95% CI: [0.127, 0.398]
95% CI: [0.036, 0.312]
95% CI: [-0.118, 0.171]
Primary
Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. Minimum FEV1 over 0-2 hrs post-allergen challenge (Minimum EAR) is the minimum value of all of the post-allergen challenge timepoints up to and including 2 hours post-allergen challenge (i.e., minimum over 5 minutes (min), 10 min, 15 min, 20 min, 30 min, 45 min and 1 hr, 1.5 hrs, and 2 hrs. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.
Time frame: Day 21 of each treatment period (up to Study Day 197)
Population: Efficacy Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -1.091 Liters |
| FF/VI 100/25 µg OD | Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.614 Liters |
| FF 100 µg OD | Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.826 Liters |
| VI 25 µg OD | Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.955 Liters |
95% CI: [0.031, 0.393]
95% CI: [0.147, 0.536]
95% CI: [0.282, 0.672]
95% CI: [0.066, 0.463]
95% CI: [-0.072, 0.343]
Primary
LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hour after dosing on Day 21. LAR FEV1 was measured 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs post-allergen challenge on Day 21. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.
Time frame: Day 21 of each treatment period (up to Study Day 197)
Population: Efficacy Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.466 Liters |
| FF/VI 100/25 µg OD | LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | 0.018 Liters |
| FF 100 µg OD | LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | 0.018 Liters |
| VI 25 µg OD | LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.298 Liters |
95% CI: [0.332, 0.636]
95% CI: [0.33, 0.638]
95% CI: [0.009, 0.327]
95% CI: [-0.14, 0.14]
95% CI: [0.168, 0.464]
Primary
Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period
Forced expiratory volume in one second (FEV1) is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen (administered by inhalation) 1 hr after dosing on Day 21. Minimum FEV1 over 4-10 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 4 and 10 hrs post-allergen challenge, inclusive of the 4 hr and 10 hr timepoints (i.e., minimum over 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs). Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.
Time frame: Day 21 of each treatment period (up to Study Day 197)
Population: Efficacy Population: all participants who received at least one dose of study medication, had a post-dose FEV1 assessment, and who were not major protocol violators. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.731 Liters |
| FF/VI 100/25 µg OD | Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.216 Liters |
| FF 100 µg OD | Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.188 Liters |
| VI 25 µg OD | Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -0.536 Liters |
95% CI: [0.33, 0.701]
95% CI: [0.355, 0.73]
95% CI: [0.001, 0.388]
95% CI: [-0.198, 0.143]
95% CI: [0.14, 0.501]
Secondary
Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants were exposed to an allergen 1 hr after dosing on Day 21. FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Maximum percent change was calculated as the minimum FEV1 minus the saline FEV1 value divided by the saline FEV1 multiplied by 100. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline FEV1 value.
Time frame: Day 21 of each treatment period (up to Study Day 197)
Population: Efficacy Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -26.13 percent change |
| FF/VI 100/25 µg OD | Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -10.43 percent change |
| FF 100 µg OD | Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -16.14 percent change |
| VI 25 µg OD | Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period | -18.35 percent change |
Secondary
Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Participants inhaled doubling increments of methacholine until a \>=20% fall in FEV1 from the saline value was achieved. After inhalation of saline, 3 measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value.
Time frame: Day 22 of each treatment period (up to Study Day 198)
Population: Efficacy Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period | 1.046 milligrams per milliliter | Standard Deviation 3.3191 |
| FF/VI 100/25 µg OD | Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period | 2.500 milligrams per milliliter | Standard Deviation 3.7363 |
| FF 100 µg OD | Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period | 2.492 milligrams per milliliter | Standard Deviation 5.3371 |
| VI 25 µg OD | Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period | 0.387 milligrams per milliliter | Standard Deviation 0.5311 |