Asthma
Conditions
Keywords
Bronchodilator
Brief summary
Study to determine the bronchodilatory effects of PF-04191834 compared with zileuton in patients with asthma
Interventions
DRUGPF-04191834
30mg PF-04191834, single dose, oral dispersion + 2 x placebo tablets.
DRUGzileuton
1200mg, 2 x 600mg tablets, single dose + placebo oral dispersion, single dose.
DRUGPlacebo
2 x placebo tablets + placebo oral dispersion, single dose.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Persistent mild/moderate asthma for at least 6 months. * Reduced lung function * Reversible airway obstruction
Exclusion criteria
* Pregnant/nursing females. * Liver function tests greater than upper limit of normal (ULN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline, 12 hours (hrs) post-dose | The FEV1 is the maximal volume of air that can be forcefully exhaled in one second |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline, 12 hours (hrs) post-dose | The FVC is the maximal volume of air that can be exhaled from full inhalation by exhaling as forcefully and rapidly as possible |
| Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline, 12 hours (hrs) post-dose | The FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half-Life (t1/2) | Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period. | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period. | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | 14 and 24 hours following dosing in each period. | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period. | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period. | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants receiving any of the 5 treatments (PF-04191834 30 mg, PF-04191834 100 mg, PF-04191834 2000 mg, Zileuton CR 1200 mg and Placebo) in a randomized fashion first | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Intervention Period 4 | Adverse Event | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age Continuous | 33.5 years STANDARD_DEVIATION 9.7 |
| Race/Ethnicity, Customized Black | 3 participants |
| Race/Ethnicity, Customized White | 12 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 15 | 4 / 14 | 10 / 15 | 4 / 15 | 12 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
The FEV1 is the maximal volume of air that can be forcefully exhaled in one second
Time frame: Baseline, 12 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.624 L | Standard Deviation 0.3939 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 12 Hours Postdose | 0.064 L | Standard Deviation 0.3098 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.626 L | Standard Deviation 0.386 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 12 Hours Postdose | 0.164 L | Standard Deviation 0.1859 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.585 L | Standard Deviation 0.52 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 12 Hours Postdose | 0.152 L | Standard Deviation 0.2072 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 12 Hours Postdose | 0.265 L | Standard Deviation 0.3047 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.579 L | Standard Deviation 0.4131 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.609 L | Standard Deviation 0.4502 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 12 Hours Postdose | 0.131 L | Standard Deviation 0.1566 |
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
The FEV1 is the maximal volume of air that can be forcefully exhaled in one second
Time frame: Baseline, 24 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.624 L | Standard Deviation 0.3939 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 24 Hours Postdose | 0.122 L | Standard Deviation 0.2553 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.626 L | Standard Deviation 0.386 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 24 Hours Postdose | 0.014 L | Standard Deviation 0.2318 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.585 L | Standard Deviation 0.52 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 24 Hours Postdose | 0.103 L | Standard Deviation 0.2616 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 24 Hours Postdose | 0.162 L | Standard Deviation 0.1559 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.579 L | Standard Deviation 0.4131 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.609 L | Standard Deviation 0.4502 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Change at 24 Hours Postdose | 0.151 L | Standard Deviation 0.1338 |
Secondary
Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75)
The FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity
Time frame: Baseline, 24 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.951 L | Standard Deviation 0.455 |
| Placebo | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 24 Hours Postdose | 0.146 L | Standard Deviation 0.3049 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.901 L | Standard Deviation 0.4228 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 24 Hours Postdose | 0.038 L | Standard Deviation 0.1952 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.807 L | Standard Deviation 0.4452 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 24 Hours Postdose | 0.196 L | Standard Deviation 0.2169 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 24 Hours Postdose | 0.151 L | Standard Deviation 0.203 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.915 L | Standard Deviation 0.4488 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.959 L | Standard Deviation 0.4378 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 24 Hours Postdose | 0.208 L | Standard Deviation 0.3483 |
Secondary
Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75)
The FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity
Time frame: Baseline, 12 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.951 L/Sec | Standard Deviation 0.455 |
| Placebo | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 12 Hours Postdose | 0.091 L/Sec | Standard Deviation 0.3556 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.901 L/Sec | Standard Deviation 0.4228 |
| PF-04191834 30 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 12 Hours Postdose | 0.340 L/Sec | Standard Deviation 0.4238 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.807 L/Sec | Standard Deviation 0.4452 |
| PF-04191834 100 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 12 Hours Postdose | 0.269 L/Sec | Standard Deviation 0.3033 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 12 Hours Postdose | 0.297 L/Sec | Standard Deviation 0.3871 |
| PF-04191834 2000 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.915 L/Sec | Standard Deviation 0.4488 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Baseline | 1.959 L/Sec | Standard Deviation 0.4378 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Expiratory Flow Between 25 and 75% of Vital Capacity (FEF25-75) | Change at 12 Hours Postdose | 0.187 L/Sec | Standard Deviation 0.3757 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC)
The FVC is the maximal volume of air that can be exhaled from full inhalation by exhaling as forcefully and rapidly as possible
Time frame: Baseline,24 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.852 L | Standard Deviation 0.8865 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Change at 24 Hours Postdose | 0.162 L | Standard Deviation 0.2322 |
| PF-04191834 30 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.891 L | Standard Deviation 0.8625 |
| PF-04191834 30 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 24 Hours Postdose | 0.051 L | Standard Deviation 0.2839 |
| PF-04191834 100 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.720 L | Standard Deviation 0.893 |
| PF-04191834 100 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 24 Hours Postdose | 0.229 L | Standard Deviation 0.3657 |
| PF-04191834 2000 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 24 Hours Postdose | 0.171 L | Standard Deviation 0.207 |
| PF-04191834 2000 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.792 L | Standard Deviation 0.91 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.821 L | Standard Deviation 0.9914 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 24 Hours Postdose | 0.219 L | Standard Deviation 0.2977 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC)
The FVC is the maximal volume of air that can be exhaled from full inhalation by exhaling as forcefully and rapidly as possible
Time frame: Baseline, 12 hours (hrs) post-dose
Population: All enrolled participants treated who had at least 1 concentration in at least 1 treatment period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.852 L | Standard Deviation 0.8865 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) | Change at 12 Hours Postdose | 0.025 L | Standard Deviation 0.3306 |
| PF-04191834 30 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.891 L | Standard Deviation 0.8625 |
| PF-04191834 30 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 12 Hours Postdose | 0.284 L | Standard Deviation 0.415 |
| PF-04191834 100 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.720 L | Standard Deviation 0.893 |
| PF-04191834 100 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 12 Hours Postdose | 0.210 L | Standard Deviation 0.4792 |
| PF-04191834 2000 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 12 Hours Postdose | 0.266 L | Standard Deviation 0.3184 |
| PF-04191834 2000 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.792 L | Standard Deviation 0.91 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Vital Capacity (FVC) | Baseline | 3.821 L | Standard Deviation 0.9914 |
| Zileuton CR 1200 mg | Change From Baseline in Forced Vital Capacity (FVC) | Change at 12 Hours Postdose | 0.140 L | Standard Deviation 0.275 |
Other Pre-specified
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)]
AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8).
Time frame: 14 and 24 hours following dosing in each period.
Population: Since the PK sample collection only occurred until 24 hours and the approximate t1/2 at all doses appeared to be \>10 hours, t1/2 and area under the plasma concentration versus time curve until infinity (AUCinf) are not reported at any dose level.
Other Pre-specified
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time frame: Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period.
Population: All enrolled subjects treated who have at least one of the PK parameters of interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1979 ng*h/mL | Standard Deviation 482 |
| PF-04191834 30 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 5547 ng*h/mL | Standard Deviation 1388 |
| PF-04191834 100 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 29990 ng*h/mL | Standard Deviation 8812 |
Other Pre-specified
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period.
Population: All enrolled subjects treated who have at least one of the PK parameters of interest in at least one treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) | 154 ng/mL | Standard Deviation 29 |
| PF-04191834 30 mg | Maximum Observed Plasma Concentration (Cmax) | 426 ng/mL | Standard Deviation 118 |
| PF-04191834 100 mg | Maximum Observed Plasma Concentration (Cmax) | 2146 ng/mL | Standard Deviation 410 |
Other Pre-specified
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period.
Population: Since the PK sample collection only occurred until 24 hours and the approximate t1/2 at all doses appeared to be \>10 hours, t1/2 and area under the plasma concentration versus time curve until infinity (AUCinf) are not reported at any dose level.
Other Pre-specified
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Pre-dose, 2, 4, 5, 6, 10, 14 and 24 hours following dosing in each period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6 hrs |
| PF-04191834 30 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6 hrs |
| PF-04191834 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 10 hrs |