Trial Outcomes & Findings for Single Dose Study of the Effect of Formoterol Fumarate in Combination With Mometasone Furoate Inhaled Via a Pressurized Metered Dose Inhaler (pMDI) in Children Aged 5-11 Years Old With Persistent Asthma (NCT NCT00746330)
NCT ID: NCT00746330
Last Updated: 2011-06-07
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
From 0 to 12 Hours (0-12h) post-dose, after each treatment administered (approximately 1 treatment a week for 4 weeks of treatment).
Results posted on
2011-06-07
Participant Flow
Participant milestones
| Measure |
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 Pressurized Metered Dose Inhaler (pMDI) + placebo to formoterol fumarate via Dry Powder Inhaler (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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
7
|
9
|
9
|
7
|
|
Period 1
COMPLETED
|
7
|
9
|
8
|
7
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Period 2
STARTED
|
7
|
9
|
8
|
7
|
|
Period 2
COMPLETED
|
7
|
9
|
8
|
7
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
7
|
9
|
8
|
7
|
|
Period 3
COMPLETED
|
7
|
9
|
8
|
7
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
7
|
9
|
8
|
7
|
|
Period 4
COMPLETED
|
7
|
9
|
8
|
7
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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 Pressurized Metered Dose Inhaler (pMDI) + placebo to formoterol fumarate via Dry Powder Inhaler (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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|
|
Period 1
Abnormal test procedure result
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Single Dose Study of the Effect of Formoterol Fumarate in Combination With Mometasone Furoate Inhaled Via a Pressurized Metered Dose Inhaler (pMDI) in Children Aged 5-11 Years Old With Persistent Asthma
Baseline characteristics by cohort
| Measure |
F12M, PL, F12D, MFF
n=7 Participants
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.
|
F12D, F12M, MFF, PL
n=9 Participants
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.
|
MFF, F12D, PL, F12M
n=9 Participants
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.
|
PL, MFF, F12M, F12D
n=7 Participants
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.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
7 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
32 Participants
n=31 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Age Continuous
|
9.0 years
STANDARD_DEVIATION 1.63 • n=99 Participants
|
9.4 years
STANDARD_DEVIATION 1.51 • n=107 Participants
|
7.9 years
STANDARD_DEVIATION 1.83 • n=206 Participants
|
10.1 years
STANDARD_DEVIATION 1.21 • n=7 Participants
|
9.1 years
STANDARD_DEVIATION 1.72 • n=31 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
17 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
15 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
21 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 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
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
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
n=31 Participants
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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 .042 • Interval 1.69 to 1.86
|
1.77 liters
95% Confidence Interval .042 • Interval 1.69 to 1.85
|
1.80 liters
95% Confidence Interval .042 • Interval 1.72 to 1.89
|
1.71 liters
95% Confidence Interval .042 • Interval 1.62 to 1.79
|
SECONDARY outcome
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dosePopulation: Full Analysis Set
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.
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
n=31 Participants
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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
Interval 1.75 to 1.84
|
1.80 liters
Interval 1.75 to 1.85
|
1.82 liters
Interval 1.77 to 1.87
|
1.69 liters
Interval 1.64 to 1.74
|
|
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
Interval 1.75 to 1.87
|
1.80 liters
Interval 1.74 to 1.86
|
1.86 liters
Interval 1.79 to 1.92
|
1.72 liters
Interval 1.66 to 1.78
|
|
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
Interval 1.73 to 1.88
|
1.79 liters
Interval 1.71 to 1.87
|
1.84 liters
Interval 1.76 to 1.92
|
1.72 liters
Interval 1.64 to 1.8
|
|
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
Interval 1.7 to 1.79
|
1.77 liters
Interval 1.72 to 1.81
|
1.77 liters
Interval 1.73 to 1.82
|
1.68 liters
Interval 1.63 to 1.72
|
|
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
Interval 1.74 to 1.87
|
1.79 liters
Interval 1.72 to 1.85
|
1.85 liters
Interval 1.79 to 1.91
|
1.73 liters
Interval 1.67 to 1.79
|
|
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
Interval 1.69 to 1.83
|
1.75 liters
Interval 1.69 to 1.82
|
1.79 liters
Interval 1.72 to 1.86
|
1.70 liters
Interval 1.63 to 1.77
|
|
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
Interval 1.67 to 1.78
|
1.71 liters
Interval 1.65 to 1.76
|
1.76 liters
Interval 1.7 to 1.81
|
1.66 liters
Interval 1.61 to 1.72
|
SECONDARY outcome
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dosePopulation: Full Analysis Set
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.
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
n=31 Participants
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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
Interval 2.04 to 2.14
|
2.09 liters
Interval 2.05 to 2.14
|
2.09 liters
Interval 2.04 to 2.13
|
2.08 liters
Interval 2.03 to 2.13
|
|
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
Interval 2.07 to 2.17
|
2.11 liters
Interval 2.06 to 2.16
|
2.11 liters
Interval 2.06 to 2.16
|
2.08 liters
Interval 2.03 to 2.13
|
|
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
Interval 2.09 to 2.2
|
2.09 liters
Interval 2.03 to 2.14
|
2.15 liters
Interval 2.09 to 2.21
|
2.10 liters
Interval 2.04 to 2.15
|
|
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
Interval 2.05 to 2.17
|
2.08 liters
Interval 2.02 to 2.14
|
2.14 liters
Interval 2.08 to 2.2
|
2.11 liters
Interval 2.05 to 2.17
|
|
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
Interval 2.06 to 2.17
|
2.08 liters
Interval 2.02 to 2.14
|
2.12 liters
Interval 2.07 to 2.18
|
2.11 liters
Interval 2.05 to 2.17
|
|
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
Interval 2.04 to 2.15
|
2.09 liters
Interval 2.04 to 2.15
|
2.10 liters
Interval 2.04 to 2.15
|
2.09 liters
Interval 2.04 to 2.15
|
|
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
Interval 2.01 to 2.13
|
2.05 liters
Interval 1.99 to 2.11
|
2.09 liters
Interval 2.03 to 2.15
|
2.06 liters
Interval 2.0 to 2.12
|
SECONDARY outcome
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dosePopulation: Full Analysis Set
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
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
n=31 Participants
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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
Interval 238.31 to 254.99
|
248.17 liters
Interval 239.72 to 256.63
|
250.05 liters
Interval 241.48 to 258.62
|
237.85 liters
Interval 229.4 to 246.3
|
|
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
Interval 245.56 to 265.81
|
253.37 liters
Interval 243.14 to 263.59
|
257.81 liters
Interval 247.48 to 268.14
|
243.59 liters
Interval 233.36 to 253.82
|
|
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
Interval 250.97 to 271.38
|
257.08 liters
Interval 246.79 to 267.38
|
262.95 liters
Interval 252.47 to 273.43
|
248.24 liters
Interval 237.94 to 258.54
|
|
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
Interval 250.74 to 272.17
|
259.28 liters
Interval 248.45 to 270.1
|
267.91 liters
Interval 256.98 to 278.84
|
248.88 liters
Interval 238.05 to 259.7
|
|
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
Interval 253.09 to 276.26
|
258.92 liters
Interval 247.24 to 270.6
|
265.20 liters
Interval 253.42 to 276.98
|
249.07 liters
Interval 237.39 to 260.76
|
|
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
Interval 246.21 to 269.72
|
255.27 liters
Interval 247.41 to 267.12
|
262.61 liters
Interval 250.65 to 274.56
|
248.47 liters
Interval 236.61 to 260.33
|
|
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
Interval 243.94 to 267.02
|
250.71 liters
Interval 239.06 to 262.37
|
259.71 liters
Interval 248.05 to 271.37
|
244.13 liters
Interval 232.59 to 255.66
|
SECONDARY outcome
Timeframe: 5, 30 Minutes and 1, 2, 4, 8 and 12 Hours Post-dosePopulation: 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.
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.
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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
|
0 pmol/L
Standard Deviation 0
|
0 pmol/L
Standard Deviation 0
|
—
|
|
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
|
16.3 pmol/L
Standard Deviation 18.6
|
18.56 pmol/L
Standard Deviation 9.19
|
—
|
|
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
|
6.66 pmol/L
Standard Deviation 5.7
|
6.83 pmol/L
Standard Deviation 4.76
|
—
|
|
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
|
24.7 pmol/L
Standard Deviation 18.7
|
23.1 pmol/L
Standard Deviation 11.08
|
—
|
|
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
|
17.7 pmol/L
Standard Deviation 10.5
|
17.4 pmol/L
Standard Deviation 6.44
|
—
|
|
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
|
11.0 pmol/L
Standard Deviation 5.3
|
11.3 pmol/L
Standard Deviation 4.42
|
—
|
SECONDARY outcome
Timeframe: 0 to 3 hrs and 0-12 hrsPopulation: 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.
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.
Outcome measures
| Measure |
MFF10
n=32 Participants
Formoterol fumarate 10μg/Mometasone furoate 100μg via pMDI
|
F12M
n=31 Participants
Formoterol fumarate 12 μg via pMDI/ Placebo via DPI
|
F12D
n=30 Participants
Placebo via pMDI/ Formoterol fumarate 12 μg via DPI
|
Placebo
Placebo via pMDI/ Placebo via DPI
|
|---|---|---|---|---|
|
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
Interval 0.81 to 1.59
|
1.50 nmol
Interval 1.08 to 2.08
|
1.33 nmol
Interval 0.96 to 1.85
|
—
|
|
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
Interval 0.2 to 0.49
|
0.52 nmol
Interval 0.33 to 0.8
|
0.42 nmol
Interval 0.27 to 0.65
|
—
|
Adverse Events
F12M
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
F12D
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
MFF10
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER