Asthma
Conditions
Keywords
asthma, GSK2190915
Brief summary
The primary objective of this study is to evaluate the efficacy and safety of adding GSK2190915 100mg, GSK2190915 300mg or placebo tablets administered once daily to fluticasone propionate 100mcg inhalation administered twice daily in uncontrolled asthmatic subjects \> or = 12 years of age over the course of 6 weeks treatment. The secondary objectives are to undertake an exploratory analysis of the efficacy and safety of adding montelukast 10mg administered once daily or salmeterol 50mcg administered twice daily to fluticasone propionate 100mcg inhalation administered twice daily and to investigate the pharmacokinetics and pharmacodynamics of GSK2190915 in uncontrolled asthmatic subjects \> or = 12 years of age over the course of 6 weeks treatment.
Interventions
DRUGFP 100
FP 100mcg BID
DRUGGSK2190915 100
GSK2190915 100mg QD (AM)
DRUGGSK2190915 300
GSK2190915 300mg QD (AM)
DRUGmontelukast
montelukast 10mg QD (PM)
DRUGplacebo
placebo BID
DRUGFP/SAL 100/50
FP/SAL 100/50mcg BID
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age: 12 years of age or older * Non-, former or current smokers with a documented smoking history of ≤ 10 pack years * Asthma diagnosis as defined by the National Institutes of Health * Best FEV1 of 50% to \<80% of the predicted normal value * Post-albuterol FEV1/FVC ratio of \>0.70 at Visit 1/1a (between 5:00AM and 12:00 noon) * ≥ 12% and ≥200mL reversibility of FEV1 * Must have been using FP 100mcg inhalation powder BID for at least 2 weeks just prior to Visit 1. * Must be able to replace their current short-acting beta2-agonists with albuterol inhalation aerosol * Must be able and willing to give written informed consent to take part in the study. * Must be able and willing to comply with all aspects of the study including completion of daily e-Diary.
Exclusion criteria
* History of life-threatening asthma * Recent asthma exacerbation * Concurrent respiratory disease * Recent respiratory infection * Liver disease * Other concurrent diseases/abnormalities * Oral candidiasis * Drug allergy * Milk protein allergy * Immunosuppressive Medications * Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1 * OATP1B1 substrates within 4 weeks of Visit 1 * Cytochrome P450 3A4 (CYP 3A4) Inhibitors * Cytochrome P450 3A4 (CYP 3A4) Inducers * Investigational Medications * Compliance: any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol * Affiliation with Investigator's Site
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | End of Week 6 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically using spirometry, prior to study medication and any rescue albuterol (bronchodilator) use. At the end of the 6-week treatment period, FEV1 was measured approximately 24 hours after the participant's last morning dose of study medication and approximately 12 hours after the evening dose of study medication. Trough FEV1 was analyzed using mixed effect analysis of covariance (ANCOVA) model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effect of participant. Intent-to-Treat Population is defined as all participants who were randomized and received at least one dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups | Week 4 to Week 6 | The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every morning and evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily average of morning and evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. This outcome measure explored the efficacy between GSK2190915 and montelukast due to the dosing time difference. |
| Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Daytime and night time asthma symptoms were recorded every evening at bedtime and every morning upon rising, respectively, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on scales ranging from '0' (implying no symptoms) to either 5 (for daytime symptoms) or 4 (for night time symptoms) (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. 24-hour period asthma symptom scores were averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | A SABA (albuterol) was provided to participants as a rescue medication, to use as needed for symptomatic relief of asthma symptoms. Participants were required to record their albuterol use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The daily rescue SABA use was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Daytime asthma symptoms were recorded every evening at bedtime, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 6-point scale ranging from '0' (implying no symptoms) to 5 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of days when symptoms were not experienced (symptom-free days) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | The PEF is a measure of lung function and measures how fast a person can breathe out. Trough PEF was measured every morning prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily electronic diary (eDiary). Daily trough morning PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of days when rescue medication was not used (rescue-free days) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of nights when rescue medication was not used (rescue-free nights) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale: 0 = no symptoms during the night, 1 = symptoms causing to wake once, 2 = symptoms causing to wake twice or more, 3 = symptoms causing to be awake most of the night, 4 = could not sleep due to severe symptoms. Participants recorded the symptoms in a daily eDiary. The number of nights with no awakenings due to asthma during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
| Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | Week 4 to Week 6 | Participants were withdrawn if they met any of the following three criteria for 'lack of efficacy': 1) Clinic FEV1 below the FEV1 'Stability Limit' value, 2) During any consecutive 7-day period, the participant experienced PEF fallen below the PEF 'Stability Limit' for more than 3 days, or if \>= 12 inhalations per day of albuterol were used for more than 2 days, and 3) Ashtma exacerbation. The number of withdrawals due to lack of efficacy were summarized for each treatment and Fisher's Exact test was used for comparison with placebo add-on. Withdrawals occurring during active washout periods are not included. |
| Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | Week 4 to Week 6 | Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale ranging from '0' (implying no symptoms) to 4 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of nights when symptoms were not experienced (symptom-free nights) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. |
Countries
United States
Participant flow
Recruitment details
A total of 341 participants (par.) were screened, and 162 participants were randomized. A protocol amendment necessitated withdrawal of all male participants and further enrollment of female participants only.
Pre-assignment details
Par. meeting screening criteria, self-administered open-label fluticasone propionate 100 micrograms (µg) twice daily for 14-28 days. Eligible par. were assigned to 1 of 10 treatment sequences, receiving 4 of 5 double-blind treatments. Par. aged 12-14 years did not receive montelukast. Rescue medication (albuterol inhalation) was provided.
Participants by arm
| Arm | Count |
|---|---|
| All Treatments Combined In a total of 4 treatment periods (each of 6 weeks - the first 3 weeks considered as active washout), participants received 4 of the 5 possible treatments (A/B/C/D/E) in a double-blind double-dummy, cross-over manner. Fluticasone propionate (FP) 100 µg oral inhalation was a part of each treatment. Added regimen were, A: GSK2190915 100 milligrams (mg) once daily (OD), B: GSK2190915 300 mg OD, C: montelukast 10 mg OD, D: placebo twice daily (BID), E: salmeterol 50 µg and placebo BID. Albuterol aerosol was provided as a rescue inhalation. | 162 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 36 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | other Sponsor Decision (Protocol Amendme | 11 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | All Treatments Combined |
|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 14.43 |
| Race/Ethnicity, Customized African American/African Heritage | 42 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants |
| Race/Ethnicity, Customized Mixed Race | 2 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 115 Participants |
| Sex: Female, Male Female | 151 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 104 | 3 / 103 | 4 / 96 | 1 / 99 | 1 / 104 |
| serious Total, serious adverse events | 0 / 104 | 1 / 103 | 0 / 96 | 0 / 99 | 0 / 104 |
Outcome results
Primary
Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically using spirometry, prior to study medication and any rescue albuterol (bronchodilator) use. At the end of the 6-week treatment period, FEV1 was measured approximately 24 hours after the participant's last morning dose of study medication and approximately 12 hours after the evening dose of study medication. Trough FEV1 was analyzed using mixed effect analysis of covariance (ANCOVA) model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effect of participant. Intent-to-Treat Population is defined as all participants who were randomized and received at least one dose of study drug.
Time frame: End of Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | 2.36 Liters (L) | Standard Error 0.03 |
| FP + GSK2190915 100 mg | Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | 2.39 Liters (L) | Standard Error 0.03 |
| FP + GSK2190915 300 mg | Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | 2.40 Liters (L) | Standard Error 0.03 |
| FP + Montelukast | Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | 2.42 Liters (L) | Standard Error 0.03 |
| FP / Salmeterol | Trough (AM Pre-dose and Pre-rescue Bronchodilator) Forced Expiratory Volume in 1 Second (FEV1) at the End of the 6-week Treatment Period | 2.43 Liters (L) | Standard Error 0.03 |
p-value: =0.26895% CI: [-0.02, 0.07]Mixed Models Analysis
p-value: =0.0895% CI: [0, 0.09]Mixed Models Analysis
p-value: =0.01795% CI: [0.01, 0.1]Mixed Models Analysis
p-value: =0.00295% CI: [0.03, 0.12]Mixed Models Analysis
Secondary
Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period
Daytime and night time asthma symptoms were recorded every evening at bedtime and every morning upon rising, respectively, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on scales ranging from '0' (implying no symptoms) to either 5 (for daytime symptoms) or 4 (for night time symptoms) (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. 24-hour period asthma symptom scores were averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.26 Score on a scale | Standard Error 0.12 |
| FP + GSK2190915 100 mg | Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.26 Score on a scale | Standard Error 0.12 |
| FP + GSK2190915 300 mg | Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.15 Score on a scale | Standard Error 0.12 |
| FP + Montelukast | Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.22 Score on a scale | Standard Error 0.12 |
| FP / Salmeterol | Daily Asthma Symptom Score Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.25 Score on a scale | Standard Error 0.12 |
p-value: =0.95795% CI: [-0.18, 0.17]Mixed Models Analysis
p-value: =0.21395% CI: [-0.28, 0.06]Mixed Models Analysis
p-value: =0.64795% CI: [-0.2, 0.12]Mixed Models Analysis
p-value: =0.89495% CI: [-0.17, 0.15]Mixed Models Analysis
Secondary
Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups
The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every morning and evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily average of morning and evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant. This outcome measure explored the efficacy between GSK2190915 and montelukast due to the dosing time difference.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups | 352.37 L/min | Standard Error 3.9 |
| FP + GSK2190915 100 mg | Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups | 356.16 L/min | Standard Error 3.91 |
| FP + GSK2190915 300 mg | Daily (Average of Morning and Evening) PEF Averaged Over the Last 3 Weeks of the 6 -Week Treatment Period Between GSK2190915 and Montelukast Groups | 356.52 L/min | Standard Error 3.9 |
95% CI: [-9.36, 1.06]
95% CI: [-6.22, 5.5]
Secondary
Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period
The PEF is a measure of lung function and measures how fast a person can breathe out. PEF was measured every evening prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily eDiary. Daily evening PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 354.06 L/min | Standard Error 4.03 |
| FP + GSK2190915 100 mg | Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 355.71 L/min | Standard Error 4.02 |
| FP + GSK2190915 300 mg | Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 359.16 L/min | Standard Error 4.03 |
| FP + Montelukast | Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 358.88 L/min | Standard Error 4.01 |
| FP / Salmeterol | Daily Evening PEF Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 364.35 L/min | Standard Error 4 |
p-value: =0.56395% CI: [-3.97, 7.27]Mixed Models Analysis
p-value: =0.07295% CI: [-0.47, 10.67]Mixed Models Analysis
p-value: =0.12695% CI: [-1.37, 11.02]Mixed Models Analysis
p-value: =0.00195% CI: [4.21, 16.38]Mixed Models Analysis
Secondary
Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period
A SABA (albuterol) was provided to participants as a rescue medication, to use as needed for symptomatic relief of asthma symptoms. Participants were required to record their albuterol use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The daily rescue SABA use was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.17 Number of inhalations | Standard Error 0.13 |
| FP + GSK2190915 100 mg | Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.14 Number of inhalations | Standard Error 0.13 |
| FP + GSK2190915 300 mg | Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.03 Number of inhalations | Standard Error 0.13 |
| FP + Montelukast | Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.09 Number of inhalations | Standard Error 0.13 |
| FP / Salmeterol | Daily Rescue Short-acting beta2-agonist (SABA) Use Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 2.08 Number of inhalations | Standard Error 0.13 |
p-value: =0.81195% CI: [-0.23, 0.18]Mixed Models Analysis
p-value: =0.295% CI: [-0.34, 0.07]Mixed Models Analysis
p-value: =0.41595% CI: [-0.26, 0.11]Mixed Models Analysis
p-value: =0.35895% CI: [-0.26, 0.1]Mixed Models Analysis
Secondary
Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period
The PEF is a measure of lung function and measures how fast a person can breathe out. Trough PEF was measured every morning prior to study medication dose and any rescue albuterol (bronchodilator) use. Participants recorded PEF in a daily electronic diary (eDiary). Daily trough morning PEF was averaged over the last 3 weeks of the 6-week treatment period, and analyzed using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 349.19 Liters/minute (L/min) | Standard Error 4.08 |
| FP + GSK2190915 100 mg | Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 350.14 Liters/minute (L/min) | Standard Error 4.06 |
| FP + GSK2190915 300 mg | Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 354.96 Liters/minute (L/min) | Standard Error 4.07 |
| FP + Montelukast | Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 354.17 Liters/minute (L/min) | Standard Error 4.05 |
| FP / Salmeterol | Daily Trough (Morning Pre-dose and Pre-rescue Bronchodilator) Morning Peak Expiratory Flow (PEF) Averaged Over the Last 3 Weeks of the 6-week Treatment Period | 361.33 Liters/minute (L/min) | Standard Error 4.05 |
p-value: =0.75195% CI: [-4.91, 6.81]Mixed Models Analysis
p-value: =0.04995% CI: [0.03, 11.51]Mixed Models Analysis
p-value: =0.12395% CI: [-1.35, 11.32]Mixed Models Analysis
p-value: <0.00195% CI: [5.93, 18.35]Mixed Models Analysis
Secondary
Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period
Participants were withdrawn if they met any of the following three criteria for 'lack of efficacy': 1) Clinic FEV1 below the FEV1 'Stability Limit' value, 2) During any consecutive 7-day period, the participant experienced PEF fallen below the PEF 'Stability Limit' for more than 3 days, or if \>= 12 inhalations per day of albuterol were used for more than 2 days, and 3) Ashtma exacerbation. The number of withdrawals due to lack of efficacy were summarized for each treatment and Fisher's Exact test was used for comparison with placebo add-on. Withdrawals occurring during active washout periods are not included.
Time frame: Week 4 to Week 6
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FP + Placebo | Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | 9 Number of participants |
| FP + GSK2190915 100 mg | Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | 5 Number of participants |
| FP + GSK2190915 300 mg | Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | 3 Number of participants |
| FP + Montelukast | Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | 7 Number of participants |
| FP / Salmeterol | Number of Participants Withdrawn Due to Lack of Efficacy During the Last 3 Weeks of the 6-week Treatment Period | 5 Number of participants |
p-value: =0.408Fisher Exact
p-value: =0.138Fisher Exact
p-value: =0.797Fisher Exact
p-value: =0.408Fisher Exact
Secondary
Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period
Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale: 0 = no symptoms during the night, 1 = symptoms causing to wake once, 2 = symptoms causing to wake twice or more, 3 = symptoms causing to be awake most of the night, 4 = could not sleep due to severe symptoms. Participants recorded the symptoms in a daily eDiary. The number of nights with no awakenings due to asthma during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | 37.21 Percentage of nights | Standard Error 2.87 |
| FP + GSK2190915 100 mg | Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | 38.22 Percentage of nights | Standard Error 2.85 |
| FP + GSK2190915 300 mg | Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | 40.55 Percentage of nights | Standard Error 2.85 |
| FP + Montelukast | Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | 37.70 Percentage of nights | Standard Error 2.84 |
| FP / Salmeterol | Percentage of Nights Without Awakenings Due to Asthma During the Last 3 Weeks of the 6-week Treatment Period | 38.47 Percentage of nights | Standard Error 2.85 |
p-value: =0.66895% CI: [-3.64, 5.67]Mixed Models Analysis
p-value: =0.15695% CI: [-1.29, 7.98]Mixed Models Analysis
p-value: =0.82295% CI: [-3.83, 4.82]Mixed Models Analysis
p-value: =0.55595% CI: [-2.94, 5.46]Mixed Models Analysis
Secondary
Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period
Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of days when rescue medication was not used (rescue-free days) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | 40.44 Percentage of days | Standard Error 3.05 |
| FP + GSK2190915 100 mg | Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | 42.43 Percentage of days | Standard Error 3.03 |
| FP + GSK2190915 300 mg | Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | 42.59 Percentage of days | Standard Error 3.04 |
| FP + Montelukast | Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | 42.77 Percentage of days | Standard Error 3.02 |
| FP / Salmeterol | Percentage of Rescue-free Days During the Last 3 Weeks of the 6-week Treatment Period | 41.96 Percentage of days | Standard Error 3.03 |
p-value: =0.36795% CI: [-2.35, 6.33]Mixed Models Analysis
p-value: =0.33295% CI: [-2.2, 6.49]Mixed Models Analysis
p-value: =0.27795% CI: [-1.88, 6.55]Mixed Models Analysis
p-value: =0.46795% CI: [-2.59, 5.63]Mixed Models Analysis
Secondary
Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period
Albuterol was provided as a rescue medication, and participants were required to record rescue medication use in the morning and in the evening. Participants recorded the number of inhalations of rescue medication in a daily eDiary. The number of nights when rescue medication was not used (rescue-free nights) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | 45.12 Percentage of nights | Standard Error 2.87 |
| FP + GSK2190915 100 mg | Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | 45.69 Percentage of nights | Standard Error 2.85 |
| FP + GSK2190915 300 mg | Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | 48.79 Percentage of nights | Standard Error 2.86 |
| FP + Montelukast | Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | 45.32 Percentage of nights | Standard Error 2.85 |
| FP / Salmeterol | Percentage of Rescue-free Nights During the Last 3 Weeks of the 6-week Treatment Period | 43.98 Percentage of nights | Standard Error 2.85 |
p-value: =0.78995% CI: [-3.65, 4.8]Mixed Models Analysis
p-value: =0.08795% CI: [-0.54, 7.87]Mixed Models Analysis
p-value: =0.92395% CI: [-3.84, 4.24]Mixed Models Analysis
p-value: =0.57195% CI: [-5.08, 2.81]Mixed Models Analysis
Secondary
Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period
Daytime asthma symptoms were recorded every evening at bedtime, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 6-point scale ranging from '0' (implying no symptoms) to 5 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of days when symptoms were not experienced (symptom-free days) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | 30.84 Percentage of days | Standard Error 3.04 |
| FP + GSK2190915 100 mg | Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | 33.51 Percentage of days | Standard Error 3.02 |
| FP + GSK2190915 300 mg | Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | 36.14 Percentage of days | Standard Error 3.03 |
| FP + Montelukast | Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | 34.88 Percentage of days | Standard Error 3.01 |
| FP / Salmeterol | Percentage of Symptom-free Days During the Last 3 Weeks of the 6-week Treatment Period | 35.45 Percentage of days | Standard Error 3.02 |
p-value: =0.28595% CI: [-2.24, 7.57]Mixed Models Analysis
p-value: =0.03595% CI: [0.38, 10.22]Mixed Models Analysis
p-value: =0.0995% CI: [-0.63, 8.7]Mixed Models Analysis
p-value: =0.04795% CI: [0.06, 9.14]Mixed Models Analysis
Secondary
Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period
Night time asthma symptoms were recorded every morning upon rising, before taking any rescue or study medication and before assessing the PEF. Symptoms were recorded on a 5-point scale ranging from '0' (implying no symptoms) to 4 (implying severe symptoms). Participants recorded the symptoms in a daily eDiary. The number of nights when symptoms were not experienced (symptom-free nights) during the last 3 weeks of the 6-week treatment period were counted, and percentage calculated by dividing by 21 and multiplying by 100. Analysis was done using mixed effect ANCOVA model for treatment effects, incorporating fixed effects of baseline, period, age, center, smoking status, and random effects of participant.
Time frame: Week 4 to Week 6
Population: ITT Population. Only those participants available at the specified time point were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FP + Placebo | Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | 37.21 Percentage of nights | Standard Error 2.87 |
| FP + GSK2190915 100 mg | Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | 38.22 Percentage of nights | Standard Error 2.85 |
| FP + GSK2190915 300 mg | Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | 40.55 Percentage of nights | Standard Error 2.85 |
| FP + Montelukast | Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | 37.70 Percentage of nights | Standard Error 2.84 |
| FP / Salmeterol | Percentage of Symptom-free Nights During the Last 3 Weeks of the 6 Week Treatment Period | 38.47 Percentage of nights | Standard Error 2.85 |
p-value: =0.66895% CI: [-3.64, 5.67]Mixed Models Analysis
p-value: =0.15695% CI: [-1.29, 7.98]Mixed Models Analysis
p-value: =0.82295% CI: [-3.83, 4.82]Mixed Models Analysis
p-value: =0.55595% CI: [-2.94, 5.46]Mixed Models Analysis