Bronchospasm, Activity/Exercise Induced Bronchospasm
Conditions
Keywords
asthma, bronchospasm
Brief summary
During this study, your child will need to attend up to 5 office visits and maintain regular telephone contact with the clinic. Certain office visits will include physical exams, medical history review, exercise challenge test (walking/running on a treadmill), electrocardiogram (ECG) tests, and lung function tests. All study related medications and medical examinations are provided at no cost. All study drugs are currently available by prescription to patients 4 years and older.
Interventions
Fluticasone propionate/salmeterol
DRUGFluticasone Propionate
Fluticasone Propionate
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
4 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with persistent asthma for 3 months or longer. * Experienced worsened asthma symptoms during physical activity. * Using an inhaled steroid for the previous 4 weeks or longer (such as Aerobid, Azmacort, Flovent, Pulmicort, QVAR, and Vanceril).
Exclusion criteria
* Used systemic steroids as either liquids, pills, or injections to treat asthma within the previous 3 months. * Have only intermittent, seasonal, or exercise-induced asthma, and not persistent asthma. * Admitted to a hospital within the previous 6 months due to asthma symptoms. * Any poorly controlled medical conditions that may make study participation unsafe or inappropriate in the opinion of the study physician (such as cystic fibrosis, congenital heart disease, insulin dependent diabetes, glaucoma, drug allergies, etc.) * The study physician will evaluate other medical criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Following Exercise Challenge at Week 4 | Baseline and Week 4 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Maximal percent change in FEV1 following exercise challenge was defined as the percent change from pre-exercise baseline FEV1 to the minimum FEV1 collected within one hour following exercise challenge. Maximal percent change in FEV1 following exercise challenge was mean maximal percent change from pre-exercise baseline compared between treatment groups at Treatment Week 4. FEV1 was measured 5, 10, 15, 30, and 60 minutes post-exercise. The minimum FEV1 measured across these time points, regardless of any missing time points, will be used for the calculation of maximal percent change. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning Peak Expiratory Flow (AM PEF) | Baseline and Up to Week 4 | PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Each participant was instructed to perform triplicate PEF measurements in the morning. Change from baseline was calculated as the endpoint value minus the baseline value. For AM PEF, baseline was defined as the average of the AM PEF values recorded on the day of Visit 2 (7-14 \[+ or -4\] days after Visit1) plus the 6 preceding days since AM PEF was measured in the morning. |
| Change From Baseline in Evening (PM) PEF | Baseline and up to Week 4 | PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication after the symptom measurement and any rescue albuterol/salbutamol inhalation aerosol use. Each participant was instructed to perform triplicate PEF measurements in the evening. Change from baseline was calculated as the endpoint value minus the baseline value. Baseline was defined as the average of the values from the 7 days preceding Visit 2 (7-14 \[+ or -4\] days after Visit1) since these measures were derived from data collected in the evening. |
| Four-hour Serial Post-dose FEV1 Area Under the Curve (AUC) on Treatment Day 1 | Immediately prior to dosing (0 time point), 30 minutes post-dose and 1, 2, 3, 4 hour post-dose on Day 1 | FEV1 AUC is mean AUC compared between treatment groups at Treatment Day 1. Baseline was defined as the pre-dose FEV1 measure from treatment Day 1. FEV1 AUC was calculated as the area of a trapezoid (calculated as the sum of the bases (top + bottom) divided by 2, then multiplied by width) above the baseline FEV1 area. For participants not completing a serial FEV1 measurement, the last observed post-dose FEV1 measurement was carried forward. |
| Percent of Symptom-free Days | Up to Week 4 | A symptom-free day was defined as a day with no symptoms (i.e., a score of 0, indicating no asthma symptoms during the day or previous night, recorded in the daily diary). Percent of symptom-free days was calculated as the number of symptom-free days, divided by the total number of days in the treatment period, multiplied by 100 for each participant. |
| Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Baseline (Week 0) and up to Week 4 | PAQLQ measures functional problems that are most troublesome to children with asthma. PAQLQ has 23 questions in 3 domains (activity limitation=5, emotional function=8, symptoms=10). Participants responded to each question on a 7-point scale (7= not bothered at all and 1= extremely bothered). The overall PAQLQ score is the mean of all 23 responses (minimum score 1= 5+8+10/23 and maximum score 7= 35+56+70/23) and the individual domain scores are the means of the items in those domains (minimum: 5/5, 8/8, 10/10 and maximum: 35/5, 56/8, 70/10). Minimum possible value is 1 (maximum impairment); maximum possible value is 7 (no impairment). Endpoint was defined from the last questionnaire collected during the double-blind treatment period or discontinuation visit (up to Week 4). |
| Percent of Rescue-free Days | Up to Week 4 | A rescue-free day was defined as a day when no supplemental albuterol was taken (i.e., 0 puffs recorded for both AM and PM assessments of albuterol use in the daily diary). Percent of rescue-free days was calculated as the number of rescue-free days, divided by the total number of days in the treatment period, multiplied by 100 for each participant. |
Countries
United States
Participant flow
Recruitment details
The study was conducted from 23 December 2003 to 23 April 2006 across 51 sites in the United States (US) and a total of 248 participants were randomized.
Pre-assignment details
Out of 789 participants screened, 389 participants were screen failures and 152 participants were Baseline failures.
Participants by arm
| Arm | Count |
|---|---|
| FSC 100/50mcg BID Participants received FSC 100/50 mcg one inhalation as a combination product via DISKUS, twice daily in morning after awakening and in evening for up to 28 days. | 124 |
| FP 100mcg BID Participants received FP 100 mcg one inhalation via DISKUS, twice daily in morning after awakening and in evening for up to 28 days. | 124 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 7 |
| Overall Study | Discontinued by sponsor | 1 | 1 |
| Overall Study | Exacerbation | 2 | 2 |
| Overall Study | Expired drug use | 1 | 2 |
| Overall Study | Investigator discretion | 0 | 1 |
| Overall Study | misrandomized | 1 | 1 |
| Overall Study | Non-compliance | 1 | 3 |
| Overall Study | Protocol Violation | 5 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | FSC 100/50mcg BID | FP 100mcg BID | Total |
|---|---|---|---|
| Age, Continuous | 11.1 Years STANDARD_DEVIATION 3.33 | 11.0 Years STANDARD_DEVIATION 3.57 | 11.1 Years STANDARD_DEVIATION 3.45 |
| Race/Ethnicity, Customized American Hispanic | 12 Participants | 8 Participants | 20 Participants |
| Race/Ethnicity, Customized Arabic/North African | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 26 Participants | 29 Participants | 55 Participants |
| Race/Ethnicity, Customized East & South East Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Japanese | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized South Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian | 81 Participants | 81 Participants | 162 Participants |
| Sex: Female, Male Female | 49 Participants | 50 Participants | 99 Participants |
| Sex: Female, Male Male | 75 Participants | 74 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 124 | 0 / 124 |
| other Total, other adverse events | 37 / 124 | 35 / 124 |
| serious Total, serious adverse events | 0 / 124 | 0 / 124 |
Outcome results
Primary
Maximal Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Following Exercise Challenge at Week 4
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Maximal percent change in FEV1 following exercise challenge was defined as the percent change from pre-exercise baseline FEV1 to the minimum FEV1 collected within one hour following exercise challenge. Maximal percent change in FEV1 following exercise challenge was mean maximal percent change from pre-exercise baseline compared between treatment groups at Treatment Week 4. FEV1 was measured 5, 10, 15, 30, and 60 minutes post-exercise. The minimum FEV1 measured across these time points, regardless of any missing time points, will be used for the calculation of maximal percent change.
Time frame: Baseline and Week 4
Population: Intent-to-Treat (ITT) population included all participants randomized to study drug. The number of participants available at that particular time point were used for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Maximal Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Following Exercise Challenge at Week 4 | -9.5 Percent change | Standard Error 0.83 |
| FP 100mcg BID | Maximal Percent Change in Forced Expiratory Volume in 1 Second (FEV1) Following Exercise Challenge at Week 4 | -12.7 Percent change | Standard Error 1.06 |
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for maximal percent change in FEV1 following exercise challenge at Week 4.p-value: 0.02195% CI: [0.5, 5.6]ANCOVA
Secondary
Change From Baseline in Evening (PM) PEF
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication after the symptom measurement and any rescue albuterol/salbutamol inhalation aerosol use. Each participant was instructed to perform triplicate PEF measurements in the evening. Change from baseline was calculated as the endpoint value minus the baseline value. Baseline was defined as the average of the values from the 7 days preceding Visit 2 (7-14 \[+ or -4\] days after Visit1) since these measures were derived from data collected in the evening.
Time frame: Baseline and up to Week 4
Population: ITT population. Here, 'N' denotes participants with data available at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Change From Baseline in Evening (PM) PEF | 10.8 L/min | Standard Error 2.96 |
| FP 100mcg BID | Change From Baseline in Evening (PM) PEF | 7.6 L/min | Standard Error 3.03 |
Comparison: FSC 100/50mcg BID versus FP 100mcg BID PM PEF.p-value: 0.39695% CI: [-4.8, 12.1]ANCOVA
Secondary
Change From Baseline in Morning Peak Expiratory Flow (AM PEF)
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Each participant was instructed to perform triplicate PEF measurements in the morning. Change from baseline was calculated as the endpoint value minus the baseline value. For AM PEF, baseline was defined as the average of the AM PEF values recorded on the day of Visit 2 (7-14 \[+ or -4\] days after Visit1) plus the 6 preceding days since AM PEF was measured in the morning.
Time frame: Baseline and Up to Week 4
Population: ITT population. Here, 'N' denotes participants with data available at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Change From Baseline in Morning Peak Expiratory Flow (AM PEF) | 16.3 Liters/minute (L/min) | Standard Error 2.99 |
| FP 100mcg BID | Change From Baseline in Morning Peak Expiratory Flow (AM PEF) | 9.1 Liters/minute (L/min) | Standard Error 3.86 |
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for AM PEFp-value: 0.09795% CI: [-1.5, 17.6]ANCOVA
Secondary
Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ)
PAQLQ measures functional problems that are most troublesome to children with asthma. PAQLQ has 23 questions in 3 domains (activity limitation=5, emotional function=8, symptoms=10). Participants responded to each question on a 7-point scale (7= not bothered at all and 1= extremely bothered). The overall PAQLQ score is the mean of all 23 responses (minimum score 1= 5+8+10/23 and maximum score 7= 35+56+70/23) and the individual domain scores are the means of the items in those domains (minimum: 5/5, 8/8, 10/10 and maximum: 35/5, 56/8, 70/10). Minimum possible value is 1 (maximum impairment); maximum possible value is 7 (no impairment). Endpoint was defined from the last questionnaire collected during the double-blind treatment period or discontinuation visit (up to Week 4).
Time frame: Baseline (Week 0) and up to Week 4
Population: ITT Population. The PAQLQ was administered only to participants \>=7 years old.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation week 4 | 0.93 Scores on a scale | Standard Error 0.113 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Week 2 | 0.39 Scores on a scale | Standard Error 0.085 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function Week 2 | 0.44 Scores on a scale | Standard Error 0.066 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Week 4 | 0.52 Scores on a scale | Standard Error 0.101 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation week 2 | 0.78 Scores on a scale | Standard Error 0.092 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Endpoint | 0.48 Scores on a scale | Standard Error 0.094 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function Week 4 | 0.56 Scores on a scale | Standard Error 0.096 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Week 2 | 0.49 Scores on a scale | Standard Error 0.068 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation endpoint | 0.89 Scores on a scale | Standard Error 0.104 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Week 4 | 0.62 Scores on a scale | Standard Error 0.091 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function endpoint | 0.53 Scores on a scale | Standard Error 0.09 |
| FSC 100/50mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Endpoint | 0.59 Scores on a scale | Standard Error 0.084 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Endpoint | 0.51 Scores on a scale | Standard Error 0.084 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation week 2 | 0.63 Scores on a scale | Standard Error 0.1 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation week 4 | 0.75 Scores on a scale | Standard Error 0.116 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Activity limitation endpoint | 0.67 Scores on a scale | Standard Error 0.105 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function Week 2 | 0.48 Scores on a scale | Standard Error 0.089 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function Week 4 | 0.47 Scores on a scale | Standard Error 0.097 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Emotional function endpoint | 0.42 Scores on a scale | Standard Error 0.088 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Week 2 | 0.49 Scores on a scale | Standard Error 0.081 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Week 4 | 0.55 Scores on a scale | Standard Error 0.109 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Symptoms Endpoint | 0.51 Scores on a scale | Standard Error 0.101 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Week 2 | 0.52 Scores on a scale | Standard Error 0.074 |
| FP 100mcg BID | Change From Baseline in Pediatric Asthma Quality of Life Questionnaire (PAQLQ) | Overall score Week 4 | 0.57 Scores on a scale | Standard Error 0.092 |
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for activity limitation at Week 2p-value: 0.16895% CI: [-0.08, 0.43]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for activity limitation at Week 4.p-value: 0.46595% CI: [-0.18, 0.4]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for activity limitation at Endpoint.p-value: 0.22295% CI: [-0.1, 0.42]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for emotional function at Week 2.p-value: 0.29495% CI: [-0.29, 0.09]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for emotional function at Week 4.p-value: 0.82895% CI: [-0.24, 0.19]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for emotional function at Endpoint.p-value: 0.90395% CI: [-0.19, 0.22]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for symptoms at Week 2.p-value: 0.46495% CI: [-0.3, 0.14]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for symptoms at Week 4.p-value: 0.55195% CI: [-0.32, 0.17]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for symptoms at Endpoint.p-value: 0.63395% CI: [-0.3, 0.18]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for overall score at Week 2.p-value: 0.795% CI: [-0.22, 0.15]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for overall score at Week 4.p-value: 0.8695% CI: [-0.23, 0.2]ANCOVA
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for overall score at Endpoint.p-value: 0.91995% CI: [-0.19, 0.21]ANCOVA
Secondary
Four-hour Serial Post-dose FEV1 Area Under the Curve (AUC) on Treatment Day 1
FEV1 AUC is mean AUC compared between treatment groups at Treatment Day 1. Baseline was defined as the pre-dose FEV1 measure from treatment Day 1. FEV1 AUC was calculated as the area of a trapezoid (calculated as the sum of the bases (top + bottom) divided by 2, then multiplied by width) above the baseline FEV1 area. For participants not completing a serial FEV1 measurement, the last observed post-dose FEV1 measurement was carried forward.
Time frame: Immediately prior to dosing (0 time point), 30 minutes post-dose and 1, 2, 3, 4 hour post-dose on Day 1
Population: ITT population. Here, 'N' denotes participants with data available at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Four-hour Serial Post-dose FEV1 Area Under the Curve (AUC) on Treatment Day 1 | 0.70 Liters*hour | Standard Error 0.067 |
| FP 100mcg BID | Four-hour Serial Post-dose FEV1 Area Under the Curve (AUC) on Treatment Day 1 | 0.30 Liters*hour | Standard Error 0.059 |
Comparison: FSC 100/50mcg BID versus FP 100mcg BID for post-dose FEV1 AUC Day 1.p-value: <0.00195% CI: [0.24, 0.58]ANCOVA
Secondary
Percent of Rescue-free Days
A rescue-free day was defined as a day when no supplemental albuterol was taken (i.e., 0 puffs recorded for both AM and PM assessments of albuterol use in the daily diary). Percent of rescue-free days was calculated as the number of rescue-free days, divided by the total number of days in the treatment period, multiplied by 100 for each participant.
Time frame: Up to Week 4
Population: ITT population. Here, 'N' denotes participants with data available at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Percent of Rescue-free Days | 59.4 Percentage of days | Standard Error 3.21 |
| FP 100mcg BID | Percent of Rescue-free Days | 54.7 Percentage of days | Standard Error 3.4 |
Secondary
Percent of Symptom-free Days
A symptom-free day was defined as a day with no symptoms (i.e., a score of 0, indicating no asthma symptoms during the day or previous night, recorded in the daily diary). Percent of symptom-free days was calculated as the number of symptom-free days, divided by the total number of days in the treatment period, multiplied by 100 for each participant.
Time frame: Up to Week 4
Population: ITT population. Here, 'N' denotes participants with data available at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FSC 100/50mcg BID | Percent of Symptom-free Days | 27.3 Percentage of days | Standard Error 3.1 |
| FP 100mcg BID | Percent of Symptom-free Days | 28.6 Percentage of days | Standard Error 3.04 |