Asthma
Conditions
Keywords
Amgen, chronic inflammatory disease, wheezing
Brief summary
The purpose of this study is to determine if AMG 827 is effective compared to placebo as measured by change in Asthma Control Questionnaire (ACQ) composite scores.
Interventions
DRUGPlacebo
SC injection.
DRUGAMG 827
SC injection.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Men or women 18 to 65 years of age * Percent of predicted FEV1 ≥ 50% and ≤ 80% * At least 12% reversibility over pre-bronchodilator FEV1 * Inhaled corticosteroid (ICS) ≥ 200 and ≤ 1000 µg/day fluticasone powder or equivalent * Ongoing asthma symptoms with ACQ composite score ≥ 1.5 points
Exclusion criteria
* Respiratory infection within 4 weeks of screening visit or 1 week of baseline visit * History of chronic obstructive pulmonary disease or other chronic pulmonary condition other than asthma * Any uncontrolled or clinically significant systemic disease (eg, uncontrolled diabetes, liver disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | Baseline and Week 12 | The ACQ is an instrument used in clinical research and practice to evaluate asthma control/impairment. It is a validated composite score that assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon awakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and forced expiratory volume in 1 second (FEV1). The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/limitation) scale. The total score is obtained by adding the value from each question and dividing by the number of questions. Higher scores indicates worsening of condition and a negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | Baseline and Week 12 | — |
| Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | Baseline to Week 12 | Participants recorded SABA use for 1 week prior to randomization (baseline) and the average number of days recorded was subtracted from average days of SABA use across 12 week intervention period. |
| Change From Baseline in Daily Asthma Symptom Score to Week 12 | Baseline and Week 12 | Participants recorded their daily asthma symptoms in their electronic diaries (Ediary). It included 7 questions: frequency of night time awakening, time awake at night, wheezing, shortness of breath, cough, chest tightness and activity limitation. Daily asthma symptoms score is the sum of 7 individual scores (with the total score ranging from 0-21). Higher scores indicates worsening of condition and a negative change from baseline indicates improvement. |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | Baseline and Week 12 | The AQLQ is the most commonly used asthma specific instrument and includes evaluations of both symptom and quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms (Mitchell EA et al, 1997, Juniper et al, 1994, Christie MJ et al, 1993, Juniper et al, 1993). Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score = mean of the responses to the 32 questions. Higher scores indicate better quality of life and a positive change from baseline indicates improved symptoms. |
| Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Baseline and Week 12 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FEV1 was performed both pre and post-administration of bronchodilator treatment at Baseline and Week 12. |
| Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 | Week 8 (days 60 and 64), and pre-dose on Week 10 | — |
| Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 | Week 8 (days 60 and 64), and pre-dose on Week 10 | — |
| Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 | Week 8 (days 60 and 64), and pre-dose on Week 10 | — |
| Proportion of Asthma Symptom-free Days | Up to Week 12 | Asthma symptom-free days were defined as a participant having a score of zero in their daily asthma symptom score. Asthma symptom-free days without SABA use were defined as a participant having a score of zero in their daily asthma symptom score and no SABA use. The proportion of asthma symptom-free days was calculated as the number of asthma symptom-free days over the number of days in the double-blind treatment period (12 weeks). |
Countries
Austria, Belgium, Canada, Finland, Hungary, Netherlands, Poland, Russia, South Korea, United States
Participant flow
Recruitment details
This study was conducted at 61 centers in Austria, Belgium, Canada, Finland, Hungary, Netherlands, Poland, Russia, South Korea, and the United States; 47 of these sites enrolled participants from 04 October 2010 to 21 December 2011. 315 participants were enrolled, but 10 participants from 1 site were excluded from all analyses due to major issues of Good Clinical Practice (GCP) compliance and are not included in the participant flow.
Pre-assignment details
A washout period for specific asthma medications was conducted after informed consent and prior to run-in period. After completing screening and meeting all eligibility criteria, all eligible participants underwent run-in visits for 4 weeks prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received the matching placebo administered as a subcutaneous (SC) injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | 76 |
| AMG 827 140 mg Participants received AMG 827 140 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | 74 |
| AMG 827 210 mg Participants received AMG 872 210 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | 76 |
| AMG 827 280 mg Participants received AMG 827 280 mg administered as a SC injection at Day 1 and weeks 1, 2, 4, 6, 8, and 10. | 76 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Administrative decision | 0 | 0 | 0 | 1 |
| Overall Study | Adverse Event | 0 | 3 | 1 | 4 |
| Overall Study | Full consent withdrawn | 2 | 2 | 2 | 3 |
| Overall Study | Ineligibility determined | 2 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Noncompliance | 1 | 0 | 2 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 1 |
| Overall Study | Protocol-specified criteria | 3 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | AMG 827 280 mg | AMG 827 210 mg | AMG 827 140 mg | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 45.7 Years STANDARD_DEVIATION 11.5 | 46.5 Years STANDARD_DEVIATION 11.5 | 46.0 Years STANDARD_DEVIATION 11.2 | 43.6 Years STANDARD_DEVIATION 11.6 | 46.8 Years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 3 Participants | 6 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 282 Participants | 73 Participants | 70 Participants | 66 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 31 Participants | 4 Participants | 6 Participants | 16 Participants | 5 Participants |
| Race/Ethnicity, Customized Multiple | 4 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 254 Participants | 67 Participants | 63 Participants | 55 Participants | 69 Participants |
| Sex: Female, Male Female | 179 Participants | 46 Participants | 38 Participants | 42 Participants | 53 Participants |
| Sex: Female, Male Male | 123 Participants | 30 Participants | 38 Participants | 32 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 75 | 0 / 76 | 0 / 77 |
| other Total, other adverse events | 24 / 76 | 28 / 74 | 28 / 76 | 28 / 76 |
| serious Total, serious adverse events | 1 / 76 | 3 / 74 | 1 / 76 | 2 / 76 |
Outcome results
Primary
Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12
The ACQ is an instrument used in clinical research and practice to evaluate asthma control/impairment. It is a validated composite score that assesses disease control by evaluating 7 questions: night time awakenings, asthma symptoms upon awakening, activity limitation, shortness of breath, wheeze frequency, short-acting bronchodilator use, and forced expiratory volume in 1 second (FEV1). The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/limitation) scale. The total score is obtained by adding the value from each question and dividing by the number of questions. Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | -0.427 Score on a scale | Standard Deviation 0.784 |
| AMG 827 140 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | -0.521 Score on a scale | Standard Deviation 0.796 |
| AMG 827 210 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | -0.512 Score on a scale | Standard Deviation 0.728 |
| AMG 827 280 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Composite Scores to Week 12 | -0.556 Score on a scale | Standard Deviation 0.81 |
p-value: 0.583895% CI: [-0.311, 0.175]ANCOVA
p-value: 0.539195% CI: [-0.316, 0.166]ANCOVA
p-value: 0.358395% CI: [-0.355, 0.129]ANCOVA
Secondary
Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10
Time frame: Week 8 (days 60 and 64), and pre-dose on Week 10
Population: The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 | 68.3 µg*day/mL | Standard Deviation 74.3 |
| AMG 827 140 mg | Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 | 171 µg*day/mL | Standard Deviation 150 |
| AMG 827 210 mg | Area Under the Concentration-time Curve During the Dosing Interval (AUCtau) of AMG 827 at Week 8 to 10 | 313 µg*day/mL | Standard Deviation 196 |
Secondary
Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | AM | 4.26 Litres/minute | Standard Deviation 39.22 |
| Placebo | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | PM | -0.22 Litres/minute | Standard Deviation 37.807 |
| AMG 827 140 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | PM | -11.56 Litres/minute | Standard Deviation 40.277 |
| AMG 827 140 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | AM | -14.09 Litres/minute | Standard Deviation 46.708 |
| AMG 827 210 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | AM | -4.53 Litres/minute | Standard Deviation 46.468 |
| AMG 827 210 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | PM | -9.16 Litres/minute | Standard Deviation 45.08 |
| AMG 827 280 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | AM | -1.95 Litres/minute | Standard Deviation 44.624 |
| AMG 827 280 mg | Change From Baseline in AM and PM Peak Expiratory Flow Rate (PEFR) to Week 12 | PM | -7.96 Litres/minute | Standard Deviation 37.984 |
Comparison: AMp-value: 0.026295% CI: [-31.686, -2.009]ANCOVA
Comparison: AMp-value: 0.362795% CI: [-21.239, 7.793]ANCOVA
Comparison: AMp-value: 0.450795% CI: [-19.791, 8.814]ANCOVA
Comparison: PMp-value: 0.122895% CI: [-23.686, 2.834]ANCOVA
Comparison: PMp-value: 0.309295% CI: [-19.758, 6.281]ANCOVA
Comparison: PMp-value: 0.216795% CI: [-20.831, 4.744]ANCOVA
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12
The AQLQ is the most commonly used asthma specific instrument and includes evaluations of both symptom and quality of life measures. The 32-item instrument measures 4 domains affected by asthma including activity limitations, emotional function, exposure to environmental stimuli, and symptoms (Mitchell EA et al, 1997, Juniper et al, 1994, Christie MJ et al, 1993, Juniper et al, 1993). Participants were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (7=no impairment, 1=severe impairment). The overall score = mean of the responses to the 32 questions. Higher scores indicate better quality of life and a positive change from baseline indicates improved symptoms.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | 0.626 Score on a scale | Standard Deviation 0.901 |
| AMG 827 140 mg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | 0.596 Score on a scale | Standard Deviation 0.979 |
| AMG 827 210 mg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | 0.537 Score on a scale | Standard Deviation 0.71 |
| AMG 827 280 mg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12 | 0.587 Score on a scale | Standard Deviation 0.866 |
p-value: 0.852495% CI: [-0.251, 0.303]ANCOVA
p-value: 0.813995% CI: [-0.305, 0.24]ANCOVA
p-value: 0.988195% CI: [-0.281, 0.276]ANCOVA
Secondary
Change From Baseline in Daily Asthma Symptom Score to Week 12
Participants recorded their daily asthma symptoms in their electronic diaries (Ediary). It included 7 questions: frequency of night time awakening, time awake at night, wheezing, shortness of breath, cough, chest tightness and activity limitation. Daily asthma symptoms score is the sum of 7 individual scores (with the total score ranging from 0-21). Higher scores indicates worsening of condition and a negative change from baseline indicates improvement.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Daily Asthma Symptom Score to Week 12 | -1.531 Score on a scale | Standard Deviation 3.674 |
| AMG 827 140 mg | Change From Baseline in Daily Asthma Symptom Score to Week 12 | -1.816 Score on a scale | Standard Deviation 3.25 |
| AMG 827 210 mg | Change From Baseline in Daily Asthma Symptom Score to Week 12 | -1.629 Score on a scale | Standard Deviation 2.62 |
| AMG 827 280 mg | Change From Baseline in Daily Asthma Symptom Score to Week 12 | -1.607 Score on a scale | Standard Deviation 3.238 |
p-value: 0.557795% CI: [-1.231, 0.665]ANCOVA
p-value: 0.936695% CI: [-0.904, 0.98]ANCOVA
p-value: 0.774595% CI: [-0.808, 1.084]ANCOVA
Secondary
Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. FEV1 was performed both pre and post-administration of bronchodilator treatment at Baseline and Week 12.
Time frame: Baseline and Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-Bronchodilator | 0.075 Liters (L) | Standard Deviation 0.323 |
| Placebo | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Post-Bronchodilator | -0.052 Liters (L) | Standard Deviation 0.275 |
| AMG 827 140 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Post-Bronchodilator | -0.019 Liters (L) | Standard Deviation 0.259 |
| AMG 827 140 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-Bronchodilator | 0.035 Liters (L) | Standard Deviation 0.307 |
| AMG 827 210 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Post-Bronchodilator | 0.016 Liters (L) | Standard Deviation 0.227 |
| AMG 827 210 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-Bronchodilator | 0.066 Liters (L) | Standard Deviation 0.367 |
| AMG 827 280 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-Bronchodilator | 0.058 Liters (L) | Standard Deviation 0.348 |
| AMG 827 280 mg | Change From Baseline in Pre- and Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Post-Bronchodilator | -0.032 Liters (L) | Standard Deviation 0.285 |
Comparison: Pre-Bronchodilatorp-value: 0.407695% CI: [-0.157, 0.064]ANCOVA
Comparison: Pre-Bronchodilatorp-value: 0.691595% CI: [-0.13, 0.086]ANCOVA
Comparison: Pre-Bronchodilatorp-value: 0.727195% CI: [-0.126, 0.088]ANCOVA
Comparison: Post-Bronchodilatorp-value: 0.92195% CI: [-0.086, 0.095]ANCOVA
Comparison: Post-Bronchodilatorp-value: 0.113995% CI: [-0.017, 0.157]ANCOVA
Comparison: Post-Bronchodilatorp-value: 0.642695% CI: [-0.066, 0.107]ANCOVA
Secondary
Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12
Participants recorded SABA use for 1 week prior to randomization (baseline) and the average number of days recorded was subtracted from average days of SABA use across 12 week intervention period.
Time frame: Baseline to Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations, and had non-missing baseline and post-baseline data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | -0.630 Days | Standard Deviation 2.842 |
| AMG 827 140 mg | Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | -0.187 Days | Standard Deviation 2.971 |
| AMG 827 210 mg | Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | -0.727 Days | Standard Deviation 2.941 |
| AMG 827 280 mg | Change From Baseline in the Frequency of Rescue Short Acting β-Agonist (SABA) Use to Week 12 | -0.798 Days | Standard Deviation 4.293 |
p-value: 0.515795% CI: [-0.67, 1.332]ANCOVA
p-value: 0.643495% CI: [-1.229, 0.76]ANCOVA
p-value: 0.695495% CI: [-1.196, 0.799]ANCOVA
Secondary
Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10
Time frame: Week 8 (days 60 and 64), and pre-dose on Week 10
Population: The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 | 8.11 µg/mL | Standard Deviation 6.91 |
| AMG 827 140 mg | Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 | 16.6 µg/mL | Standard Deviation 12.4 |
| AMG 827 210 mg | Maximum Observed Concentration (Cmax) of AMG 827 at Week 8 to 10 | 29.4 µg/mL | Standard Deviation 17.5 |
Secondary
Proportion of Asthma Symptom-free Days
Asthma symptom-free days were defined as a participant having a score of zero in their daily asthma symptom score. Asthma symptom-free days without SABA use were defined as a participant having a score of zero in their daily asthma symptom score and no SABA use. The proportion of asthma symptom-free days was calculated as the number of asthma symptom-free days over the number of days in the double-blind treatment period (12 weeks).
Time frame: Up to Week 12
Population: All randomized participants who received at least 1 dose of study treatment who were not excluded due to GCP violations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Proportion of Asthma Symptom-free Days | With use of SABA | 0.230 Ratio | Standard Deviation 0.299 |
| Placebo | Proportion of Asthma Symptom-free Days | Without use of SABA | 0.201 Ratio | Standard Deviation 0.294 |
| AMG 827 140 mg | Proportion of Asthma Symptom-free Days | Without use of SABA | 0.123 Ratio | Standard Deviation 0.241 |
| AMG 827 140 mg | Proportion of Asthma Symptom-free Days | With use of SABA | 0.167 Ratio | Standard Deviation 0.263 |
| AMG 827 210 mg | Proportion of Asthma Symptom-free Days | With use of SABA | 0.198 Ratio | Standard Deviation 0.293 |
| AMG 827 210 mg | Proportion of Asthma Symptom-free Days | Without use of SABA | 0.181 Ratio | Standard Deviation 0.286 |
| AMG 827 280 mg | Proportion of Asthma Symptom-free Days | With use of SABA | 0.166 Ratio | Standard Deviation 0.267 |
| AMG 827 280 mg | Proportion of Asthma Symptom-free Days | Without use of SABA | 0.146 Ratio | Standard Deviation 0.256 |
p-value: 0.121395% CI: [-0.141, 0.017]ANCOVA
p-value: 0.664395% CI: [-0.095, 0.061]ANCOVA
p-value: 0.287995% CI: [-0.121, 0.036]ANCOVA
p-value: 0.054695% CI: [-0.15, 0.001]ANCOVA
Comparison: Without use of SABAp-value: 0.907895% CI: [-0.08, 0.071]ANCOVA
Comparison: Without use of SABAp-value: 0.361695% CI: [-0.111, 0.04]ANCOVA
Secondary
Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10
Time frame: Week 8 (days 60 and 64), and pre-dose on Week 10
Population: The pharmacokinetic (PK) analyses set: all participants who received at least one dose of AMG 827 and who had at least 1 PK concentration measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 | 3.1 Days |
| AMG 827 140 mg | Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 | 3.1 Days |
| AMG 827 210 mg | Time to Maximum Observed Concentration (Tmax) of AMG 827 at Week 8 to 10 | 3.9 Days |