Asthma
Conditions
Keywords
Asthma, Children, Persistent asthma
Brief summary
This study is being conducted to compare the pharmacodynamics (bronchodilation, onset and duration of action), of a single dose of formoterol fumarate in combination with mometasone furoate to placebo in children of 5-11 years with persistent asthma. The study will also assess the bronchodilatory effect of a single dose of formoterol fumarate alone and in combination with mometasone furoate delivered via a pressurized metered dose inhaler (pMDI) to the bronchodilatory effect of formoterol fumarate delivered via a dry powder inhaler (DPI). Furthermore, pharmacokinetic assessments of plasma and urine will also be conducted throughout the study to assess systemic exposure following administration of the study medication.
Interventions
DRUGPlacebo to F12D
Placebo to formoterol fumarate DPI delivered via DPI
DRUGMometasone furoate/formoterol fumarate (MFF)
Formoterol fumarate dihydrate / mometasone furoate combination product 10 μg / 100 μg delivered via Pressurized Metered Dose Inhaler (pMDI). One dose consisted of 2 puffs x 5 μg / 50 μg.
DRUGFormoterol fumarate 12 μg pMDI (F12M)
Formoterol fumarate dihydrate 12 μg delivered via Pressurized Metered Dose Inhaler (pMDI) (1 dose = 2 puffs x 6 μg).
DRUGFormoterol fumarate 12 μg DPI (F12D)
Formoterol fumarate dihydrate 12 μg delivered via Dry Powder Inhaler (DPI).
DRUGPlacebo to F12M/MFF
Placebo to formoterol fumarate pMDI and formoterol fumarate / mometasone furoate delivered via pMDI
Sponsors
Schering-Plough
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* 5 to 11 years of age of either sex and of any race * A diagnosis (according to the Global Initiative for Asthma \[GINA\] guidelines) of persistent asthma for a period of at least 6 months prior to screening and must have been on a stable asthma regimen (daily dose unchanged) for at least 4 weeks prior to screening * β2-agonist reversibility, defined as an increase in absolute FEV1 of ≥12% within 30 minutes after administration of 200μg of salbutamol without the use of a spacer or its equivalent in accordance with ATS/ERS standards * A child must have an FEV1 of ≥ 60% and ≤ 90% of Polgar predicted when all restricted medications have been withheld for the appropriate intervals
Exclusion criteria
* Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment, whichever is longer. * History of malignancy of any organ system within past 5 years. * Pre-dose change (increase or decrease) in absolute FEV1 of 15% at Visit 2, compared with value at screening. * Hospitalized or had an emergency room treatment for an acute asthma exacerbation in the 1 month prior to Visit 1, or who had a clinical deterioration of asthma between Visits 1 and 2 that resulted in emergency treatment, hospitalization, or treatment with excluded asthma medication. * Significant medication condition or situation. * QTc \> 440 msec (boys) or \> 450 msec (girls) on electrocardiogram(ECG) assessment at screening. * Upper or lower respiratory tract infection within 4 weeks prior to screening. * Chronic conditions affecting the respiratory tract or chronic lung diseases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment | From 0 to 12 Hours (0-12h) post-dose, after each treatment administered (approximately 1 treatment a week for 4 weeks of treatment). | For FEV1 AUC(0-12h) the trapezoidal rule was applied using planned time measurements to calculate the AUC up to and including the last measurement recorded before intake of rescue medication. The AUC was standardized by dividing by the length of time for which measurements of FEV1 were included in the calculation of the AUC thus adjusting for subjects who were unable to complete the measurements during the 12-hour observation period and without inhaling rescue medication. The unit of the AUC was in L, being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose | All efficacy evaluations were based on spirometry assessments of lung function. FEV1 is the maximum amount of air expired in one second. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the (ATS / ERS) standards. |
| Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose | All efficacy evaluations were based on spirometry assessments of lung function. FVC is the volume (liters) of air that can forcibly be blown out after full inspiration. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS / ERS standards. |
| Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose | All efficacy evaluations were based on spirometry assessments of lung function. PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS/ERS standards |
| Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose | Unchanged racemic formoterol in plasma was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for plasma was 1.45 pmol/L. No non-compartmental PK analysis was performed. |
| Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 0 to 3 hrs and 0-12 hrs | Unchanged racemic formoterol in urine was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for urine was 0.0174 nmol/L expressed as free base. The amounts of unchanged formoterol excreted in urine from 0 to 3 hours (Ae0-3) and from 0 to 12 hours post-dose (Ae0-12) were calculated from the formoterol concentrations in urine and the urine volumes using non-compartmental methods. |
Countries
Colombia, Peru, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| F12M, PL, F12D, MFF Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 2: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 3: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 4: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication. | 7 |
| F12D, F12M, MFF, PL Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 2: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 3: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 4: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication. | 9 |
| MFF, F12D, PL, F12M Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 2: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI; Period 3: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 4: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication. | 9 |
| PL, MFF, F12M, F12D Participants received a single dose of each treatment in the following order, separated by a washout period of 6-7 days: Period 1: Placebo to formoterol fumarate / mometasone furoate via pMDI + placebo to formoterol fumarate via DPI; Period 2: Formoterol fumarate / mometasone furoate 10 μg / 100 μg via pMDI + placebo to formoterol fumarate via DPI; Period 3: Formoterol fumarate 12 μg via pMDI + placebo to formoterol fumarate via DPI; Period 4: Placebo to formoterol fumarate / mometasone furoate via pMDI + formoterol fumarate via DPI. Participants were allowed to continue their regular asthma maintenance inhaled corticosteroid medication throughout the study and were supplied with the short-acting β2-agonist (SABA) salbutamol as rescue medication. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Abnormal test procedure result | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | F12M, PL, F12D, MFF | F12D, F12M, MFF, PL | MFF, F12D, PL, F12M | PL, MFF, F12M, F12D | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 9 Participants | 9 Participants | 7 Participants | 32 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 9.0 years STANDARD_DEVIATION 1.63 | 9.4 years STANDARD_DEVIATION 1.51 | 7.9 years STANDARD_DEVIATION 1.83 | 10.1 years STANDARD_DEVIATION 1.21 | 9.1 years STANDARD_DEVIATION 1.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 4 Participants | 5 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 5 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 15 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 | 0 / 31 | 0 / 31 | 0 / 32 | 0 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 31 | 0 / 32 | 0 / 31 |
Outcome results
Primary
The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment
For FEV1 AUC(0-12h) the trapezoidal rule was applied using planned time measurements to calculate the AUC up to and including the last measurement recorded before intake of rescue medication. The AUC was standardized by dividing by the length of time for which measurements of FEV1 were included in the calculation of the AUC thus adjusting for subjects who were unable to complete the measurements during the 12-hour observation period and without inhaling rescue medication. The unit of the AUC was in L, being a weighted average of the acceptable FEV1 measurements recorded over 12 hours post dose
Time frame: From 0 to 12 Hours (0-12h) post-dose, after each treatment administered (approximately 1 treatment a week for 4 weeks of treatment).
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| MFF10 | The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment | 1.77 liters | 95% Confidence Interval 0.042 |
| F12M | The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment | 1.77 liters | 95% Confidence Interval 0.042 |
| F12D | The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment | 1.80 liters | 95% Confidence Interval 0.042 |
| Placebo | The Standardized Forced Expiratory Volume in 1 Second (FEV1) Using Area Under the Curve (AUC) From 0 to 12 Hours (0-12h) Post-dose by Treatment | 1.71 liters | 95% Confidence Interval 0.042 |
Secondary
Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI)
Unchanged racemic formoterol in plasma was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for plasma was 1.45 pmol/L. No non-compartmental PK analysis was performed.
Time frame: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
Population: Because of the dosing periods where formoterol was present at concentrations greater than 5% of the Cmax data for 4 subjects was excluded. A dosing error resulted in the exclusion of 1 subject and 1 subject had all data excluded from PK evaluation due to the plasma drug concentrations in conflict with the recorded randomization.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Pre-Dose (N count MFF=15,F12M=17,F12D=16) | 0 pmol/L | Standard Deviation 0 |
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 5-10 minutes (N=16, 17, 17) | 13.1 pmol/L | Standard Deviation 12.2 |
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 30 minutes - 2 hours (N=16,17,17) | 27.5 pmol/L | Standard Deviation 12.2 |
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 2 hours - 4 hours (N= 16, 17, 17) | 22.4 pmol/L | Standard Deviation 15.1 |
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 4 hours - 8 hours (N= 16, 17, 17) | 12.3 pmol/L | Standard Deviation 8.07 |
| MFF10 | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 8 hours - 12 hours (N= 16, 16, 17) | 7.74 pmol/L | Standard Deviation 5.68 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 8 hours - 12 hours (N= 16, 16, 17) | 6.66 pmol/L | Standard Deviation 5.7 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Pre-Dose (N count MFF=15,F12M=17,F12D=16) | 0 pmol/L | Standard Deviation 0 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 2 hours - 4 hours (N= 16, 17, 17) | 17.7 pmol/L | Standard Deviation 10.5 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 4 hours - 8 hours (N= 16, 17, 17) | 11.0 pmol/L | Standard Deviation 5.3 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 5-10 minutes (N=16, 17, 17) | 16.3 pmol/L | Standard Deviation 18.6 |
| F12M | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 30 minutes - 2 hours (N=16,17,17) | 24.7 pmol/L | Standard Deviation 18.7 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 5-10 minutes (N=16, 17, 17) | 18.56 pmol/L | Standard Deviation 9.19 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 30 minutes - 2 hours (N=16,17,17) | 23.1 pmol/L | Standard Deviation 11.08 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 8 hours - 12 hours (N= 16, 16, 17) | 6.83 pmol/L | Standard Deviation 4.76 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 2 hours - 4 hours (N= 16, 17, 17) | 17.4 pmol/L | Standard Deviation 6.44 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Pre-Dose (N count MFF=15,F12M=17,F12D=16) | 0 pmol/L | Standard Deviation 0 |
| F12D | Plasma Formoterol Concentrations (Pmol/L) Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | 4 hours - 8 hours (N= 16, 17, 17) | 11.3 pmol/L | Standard Deviation 4.42 |
Secondary
Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect
All efficacy evaluations were based on spirometry assessments of lung function. FEV1 is the maximum amount of air expired in one second. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the (ATS / ERS) standards.
Time frame: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 1.72 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 1.81 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 1.76 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 1.79 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 1.81 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 1.81 liters |
| MFF10 | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 1.74 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 1.79 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 1.79 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 1.80 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 1.80 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 1.77 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 1.75 liters |
| F12M | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 1.71 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 1.77 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 1.82 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 1.86 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 1.85 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 1.84 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 1.79 liters |
| F12D | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 1.76 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 1.72 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 1.66 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 1.70 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 1.69 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 1.68 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 1.72 liters |
| Placebo | Serial FEV1 Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 1.73 liters |
Secondary
Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect
All efficacy evaluations were based on spirometry assessments of lung function. FVC is the volume (liters) of air that can forcibly be blown out after full inspiration. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS / ERS standards.
Time frame: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 2.09 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 2.07 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 2.14 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 2.09 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 2.11 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 2.12 liters |
| MFF10 | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 2.12 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 2.09 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 2.05 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 2.11 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 2.09 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 2.09 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 2.08 liters |
| F12M | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 2.08 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 2.12 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 2.14 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 2.11 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 2.09 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 2.10 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 2.09 liters |
| F12D | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 2.15 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 2.06 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 2.08 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 2.08 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 2.10 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 2.11 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 2.09 liters |
| Placebo | Serial Forced Vital Capacity (FVC) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 2.11 liters |
Secondary
Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect
All efficacy evaluations were based on spirometry assessments of lung function. PEF is the greatest airflow rate achieved during forced exhalation with lungs fully inflated. At Visits 2, 3, 4 and 5, spirometry assessments were performed in the clinic at predose and again at 5 and 30 minutes and 1, 2, 4, 8 and 12 hours post-dose within ± 5 minutes of the scheduled time for the time points up to and including 60 minutes post-dose and then within ± 10 minutes for all subsequent time points. Spirometry equipment and performance of spirometric testing were in accordance with the ATS/ERS standards
Time frame: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 264.68 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 255.48 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 255.69 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 246.65 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 257.96 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 261.45 liters |
| MFF10 | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 261.18 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 259.28 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 258.92 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 250.71 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 253.37 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 248.17 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 257.08 liters |
| F12M | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 255.27 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 267.91 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 250.05 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 257.81 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 262.95 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 265.20 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 262.61 liters |
| F12D | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 259.71 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 1 hour (N=32, 31, 29, 31) | 248.24 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 12 hours | 244.13 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 8 hours | 248.47 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 30 minutes | 243.59 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 5 minutes | 237.85 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 4 hours | 249.07 liters |
| Placebo | Serial Peak Expiratory Flow Rate (PEF) Measurement (i.e. at 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dose) Following Inhalation of a Single Dose of Study Medication to Evaluate the Onset and Duration of the Bronchodilatory Effect | 2 hours | 248.88 liters |
Secondary
Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI)
Unchanged racemic formoterol in urine was assayed by LC-MS/MS. The lower limit of quantification (LLOQ) for urine was 0.0174 nmol/L expressed as free base. The amounts of unchanged formoterol excreted in urine from 0 to 3 hours (Ae0-3) and from 0 to 12 hours post-dose (Ae0-12) were calculated from the formoterol concentrations in urine and the urine volumes using non-compartmental methods.
Time frame: 0 to 3 hrs and 0-12 hrs
Population: The pharmacokinetic population which was modified by the exclusion of dosing periods where formoterol was present at a concentration in excess of 5% of the Cmax.Five subjects were excluded due to various reasons.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| MFF10 | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-3) nmol (N=15,17,17) | 0.31 nmol |
| MFF10 | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-12) nmol (N=16,17,17) | 1.14 nmol |
| F12M | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-12) nmol (N=16,17,17) | 1.50 nmol |
| F12M | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-3) nmol (N=15,17,17) | 0.52 nmol |
| F12D | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-3) nmol (N=15,17,17) | 0.42 nmol |
| F12D | Urinary Excretion of Formoterol Following a Single Dose of Formoterol Fumarate Alone and in Combination With Mometasone Furoate Via the pMDI and Formoterol Fumarate Via the Dry Powder Inhaler (DPI) | Ae (0-12) nmol (N=16,17,17) | 1.33 nmol |