Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The purpose of this study is to compare the efficacy and safety of BCT197 when added on to standard of care in adult subjects with acute respiratory exacerbations of chronic obstructive pulmonary disease requiring hospitalization. Additionally, the study will characterize the pharmacokinetics of BCT197 in adults with COPD. The total duration of the study will be 26 weeks. Subjects will receive study treatment administration over a period of 5 days after randomization. It is expected that approximately 255 subjects will complete the study and follow-up.
Interventions
DRUGBCT197
Capsules will be taken orally with fluids over a 5 day period after randomization
DRUGPlacebo
Capsules will be taken orally with fluids over a 5 day period after randomization
Sponsors
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female adults * Presence of an active exacerbation of the ongoing COPD requiring hospitalization for treatment * Subjects with a documented diagnosis of COPD C or D * Current smokers or ex-smokers * A documented history of at least one moderate or severe COPD exacerbation in the 12 months preceding the Screening Visit that required antibiotics and/or systemic corticosteroid. * Current regular treatment for COPD (for at least 2 months prior to the Screening Visit.
Exclusion criteria
* Age less than 40 years old * Current diagnosis of asthma * Subjects who have already completed treatment for the current exacerbation of COPD * Subjects currently requiring intensive care unit (ICU) and/or mechanical ventilation * Received a course of PDE4, p38 or PDE3/4 inhibitors within their respective defined washout periods.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in FEV1 to Day 7 - ITT Population | Days 1 to 7 | FEV1 data were recorded daily from Days 1 to 7 of the study using a computer-operated spirometer. Analysis was based on a linear Mixed Model for Repeated Measures (MMRM) with Change from Baseline in parameter as outcome; including treatment, visit, treatment by visit interaction, severity of airflow limitation at Baseline, blood eosinophils (%) at Baseline, time from start of current chronic obstructive pulmonary disease (COPD) exacerbation to first study treatment dosing, presence of cardiovascular comorbidities at Screening and COPD exacerbation treatment at Screening as fixed effects, and Baseline value and Baseline by visit interaction as covariates. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. Results were presented with adjusted mean (95% confidence interval). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of COPD-Related Deaths During the Study - ITT Population | Days 1 to 180 | Cumulative incidences of COPD-related deaths until Day 30/60/90/120/150/180 were obtained. |
| Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Days 3, 10, and 14 | FEV1 data were recorded daily from Days 1 to 7, and Days 10 and 14 of the study using a computer-operated spirometer. Analysis was based on a linear MMRM with Change from Baseline in parameter as outcome; including treatment, visit, treatment by visit interaction, severity of airflow limitation at Baseline, blood eosinophils (%) at Baseline, time from start of current COPD exacerbation to first study treatment dosing, presence of cardiovascular comorbidities at Screening and COPD exacerbation treatment at Screening as fixed effects, and Baseline value and Baseline by visit interaction as covariates. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. |
| Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline, Days 1 to 7, Days 10 and 14, Week 8, Week 12 and Week 26 | FEV1 data were recorded daily from Days 1 to 7 and on Days 10 and 14 and Weeks 8, 12, and 26 of the study using a computer-operated spirometer. FEV1 normalization was achieved if FEV1 returned to a value ≥ 89% of the most recent FEV1 value measured within the last 12 months outside an exacerbation (pre-study FEV1 value). Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. Percentages (%) were based on number of non-missing values as denominator. |
| Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline to Week 26 | FEV1 and FVC were recorded daily from Days 1 to 7 and on Days 10 and 14 and Weeks 8, 12, and 26 of the study using a computer-operated spirometer. FEV1/FVC normalization was achieved if FEV1/FVC returned to a value ≥ 89% of the most recent FEV1/FVC value measured within the last 12 months outside an exacerbation (pre-study FEV1/FVC value). Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. |
| Time to Improvement of 100 mL in FEV1 Over Time - ITT Population | Baseline to Week 26 | Time to improvement of 100 mL in FEV1 was defined as time (in days) from initiation of study treatment until the change in FEV1 was ≥ +100 mL. |
| Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1 to Day 14 | AUC was calculated according to the trapezoidal rule. The trapezoidal rule is a numerical method to be used to approximate the integral or the area under a curve. Using trapezoidal rule to approximate the area under a curve first involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when the upper end is replaced by a chord. The sum of these approximations gives the final numerical result of the AUC. |
| Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 1 to Day 14 | RR was normalized when it returned to a baseline plateau level achieved after the acute COPD exacerbation during the Stabilization Phase. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. |
| Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Days 1 to 14 | RR (breaths/min) was recorded over time during the acute exacerbation phase. |
| Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population | Days 1 to 29 | Recovery based on EXACT-PRO total score was defined as the first day in which a participant experiences a persistent, sustained improvement in their condition over the observed period (Day 1 to Day 29). Improvement had to be present for 7 consecutive days. The first day of the 7-day period was designated as the first day of Recovery. An EXACT total score was computed for each day of diary collection. |
| Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Days 1 to 29 | The standardized AUC of the EXACT-PRO were calculated from Day (a) to Day (b) using the trapezoidal rule. |
| Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Days 1 to 29 | Information regarding the participant's condition can be obtained through 3 domain scores embedded within the EXACT measure: Breathlessness, Cough & Sputum, and Chest Symptoms. These scores also range from 0 to 100 with higher scores indicating more severe symptoms.The standardized AUC of the EXACT-PRO were calculated from Day (a) to Day (b) using the trapezoidal rule. |
| Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population | Day 1 to End of Study (Day 180) | Follow-up time per participant (years) was defined as (date of last contact - date of first study drug administration + 1)/ 365.25. Total follow-up time (years) = sum of individual participant follow-up times. Rate was calculated as total number of positively adjudicated exacerbations divided by the total follow-up time in years of the treatment group. |
| Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population | Day 1 to Day 180 | Time to next positively adjudicated moderate/severe COPD exacerbation (in days) was defined as date when first moderate/severe COPD exacerbation symptoms started - date when current COPD exacerbation symptoms stopped, where COPD exacerbations experienced during the study were positively adjudicated by the Independent Adjudication Committee. Time to next positively adjudicated COPD exacerbation was presented in 25th percentile (95% confidence interval) as medians were not evaluable. |
| Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population | Day 1 to Day 30 | Time from hospitalization admission until the participant is medically ready for discharge (in days) = Date participant was medically ready for discharge from hospital - Date of hospitalization admission. Date of hospitalization admission' and 'Date participant was medically ready for discharge from hospital' were recorded on the 'Current COPD Exacerbation' form of the eCRF. Results were presented with 75th percentile (95% CI) due to the fact that 95% CI for the median was not evaluable. |
| Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Baseline to Week 26 | Participants completed the EXACT-PRO starting from Day 1 and recorded rescue medication use and any occurrences of COPD once a day (evening) in the diary. The percentage of days with intake of rescue medications was evaluated on the basis of the information recorded daily by the participant on the diaries. A day was considered with intake of rescue medications if the answer to the question How many puffs of rescue medication did you take since last evening? was\> 0. |
| Time to Improvement Based on the EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome (EXACT-PRO) Total Score During the Acute Exacerbation Phase - ITT Population | Days 1 to 29 | Improvement based on EXACT-PRO total score is defined as a decrease in the Rolling Average EXACT score ≥ 9 points from the previous day's maximum observed value during an event. The EXACT is a 14-item patient reported outcome (PRO) daily diary used to quantify and measure exacerbations of COPD. The health status of the participant is correlated to the global score, meaning a higher score corresponds to a more severe health status of the participant. An EXACT Total score is computed for each day of diary collection. The EXACT Total score is based on a logit scoring system with conversion to a 0 to 100 scale for ease of interpretation and use. The total score was used in the determination of exacerbation frequency, severity and duration of exacerbation. Specifically, changes in the total score were used to define onset and recovery from an exacerbation event and the magnitude of that event. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Days 1 to 5 | Descriptive summary of PK plasma concentration is presented as no-specific PK report is available. |
Countries
Bulgaria, Czechia, Germany, Hungary, Italy, Latvia, Poland, Romania, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BCT197 High Dose Regimen Participants received 75 mg BCT197 orally on Day 1. Subsequent doses with 40 mg BCT197 were administered orally on Day 3 and Day 5, respectively. All participants also received standard of care treatment for the acute exacerbation. | 87 |
| BCT197 Low Dose Regimen Participants received 40 mg BCT197 orally on Day 1. Subsequent doses with 20 mg BCT197 were administered orally on Day 3 and Day 5, respectively. All participants also received standard of care treatment for the acute exacerbation. | 93 |
| Placebo Participants received placebo orally on Day 1. Subsequent doses with placebo were administered orally on Day 3 and Day 5, respectively. All participants also received standard of care treatment for the acute exacerbation. | 86 |
| Total | 266 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 0 |
| Overall Study | Other | 2 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 8 | 2 |
Baseline characteristics
| Characteristic | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 8.34 | 63.1 years STANDARD_DEVIATION 8.68 | 64.7 years STANDARD_DEVIATION 7.06 | 63.8 years STANDARD_DEVIATION 8.07 |
| FEV1 at Screening Post-bronchodilator | 1.135 litre STANDARD_DEVIATION 0.3875 | 1.046 litre STANDARD_DEVIATION 0.4009 | 1.033 litre STANDARD_DEVIATION 0.3558 | 1.071 litre STANDARD_DEVIATION 0.3836 |
| FEV1 at Screening Pre-bronchodilator | 0.875 litre STANDARD_DEVIATION 0.3649 | 0.871 litre STANDARD_DEVIATION 0.3091 | 0.921 litre STANDARD_DEVIATION 0.2775 | 0.887 litre STANDARD_DEVIATION 0.3166 |
| FEV1/FVC at Screening Post-bronchodilator | 0.447 Ratio STANDARD_DEVIATION 0.1245 | 0.427 Ratio STANDARD_DEVIATION 0.1107 | 0.436 Ratio STANDARD_DEVIATION 0.1184 | 0.436 Ratio STANDARD_DEVIATION 0.1177 |
| FEV1/FVC at Screening Pre-bronchodilator | 0.381 Ratio STANDARD_DEVIATION 0.1109 | 0.424 Ratio STANDARD_DEVIATION 0.0982 | 0.404 Ratio STANDARD_DEVIATION 0.0972 | 0.403 Ratio STANDARD_DEVIATION 0.1025 |
| Forced Vital Capacity (FVC) at Screening Post-bronchodilator | 2.619 litre STANDARD_DEVIATION 0.8167 | 2.514 litre STANDARD_DEVIATION 0.8488 | 2.427 litre STANDARD_DEVIATION 0.7298 | 2.521 litre STANDARD_DEVIATION 0.8022 |
| Forced Vital Capacity (FVC) at Screening Pre-bronchodilator | 2.410 litre STANDARD_DEVIATION 0.8883 | 2.137 litre STANDARD_DEVIATION 0.8675 | 2.352 litre STANDARD_DEVIATION 0.7623 | 2.293 litre STANDARD_DEVIATION 0.8416 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 87 Participants | 92 Participants | 85 Participants | 264 Participants |
| Sex: Female, Male Female | 21 Participants | 26 Participants | 27 Participants | 74 Participants |
| Sex: Female, Male Male | 66 Participants | 67 Participants | 59 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 92 | 3 / 96 | 2 / 91 |
| other Total, other adverse events | 56 / 92 | 63 / 96 | 62 / 91 |
| serious Total, serious adverse events | 17 / 92 | 27 / 96 | 29 / 91 |
Outcome results
Primary
Change From Baseline in FEV1 to Day 7 - ITT Population
FEV1 data were recorded daily from Days 1 to 7 of the study using a computer-operated spirometer. Analysis was based on a linear Mixed Model for Repeated Measures (MMRM) with Change from Baseline in parameter as outcome; including treatment, visit, treatment by visit interaction, severity of airflow limitation at Baseline, blood eosinophils (%) at Baseline, time from start of current chronic obstructive pulmonary disease (COPD) exacerbation to first study treatment dosing, presence of cardiovascular comorbidities at Screening and COPD exacerbation treatment at Screening as fixed effects, and Baseline value and Baseline by visit interaction as covariates. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. Results were presented with adjusted mean (95% confidence interval).
Time frame: Days 1 to 7
Population: ITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BCT197 High Dose Regimen | Change From Baseline in FEV1 to Day 7 - ITT Population | 0.084 litre |
| BCT197 Low Dose Regimen | Change From Baseline in FEV1 to Day 7 - ITT Population | 0.115 litre |
| Placebo | Change From Baseline in FEV1 to Day 7 - ITT Population | 0.057 litre |
Comparison: Change from Baseline on Day 7p-value: 0.012Log Rank
Comparison: Change from Baseline on Day 7p-value: <0.001Log Rank
Comparison: Change from Baseline on Day 7p-value: 0.102Log Rank
Comparison: Day 7p-value: 0.50795% CI: [-0.053, 0.107]Mixed Models Analysis
Comparison: Day 7p-value: 0.14895% CI: [-0.021, 0.136]Mixed Models Analysis
Comparison: Day 7p-value: 0.44395% CI: [-0.109, 0.048]Mixed Models Analysis
Secondary
Area Under the Curve (AUC) of FEV1 Over Time - ITT Population
AUC was calculated according to the trapezoidal rule. The trapezoidal rule is a numerical method to be used to approximate the integral or the area under a curve. Using trapezoidal rule to approximate the area under a curve first involves dividing the area into a number of strips of equal width. Then, approximating the area of each strip by the area of the trapezium formed when the upper end is replaced by a chord. The sum of these approximations gives the final numerical result of the AUC.
Time frame: Day 1 to Day 14
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BCT197 High Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-7 | 1.232 mg/(mL*min) | Standard Deviation 0.4296 |
| BCT197 High Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-14 | 1.293 mg/(mL*min) | Standard Deviation 0.4743 |
| BCT197 High Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-3 | 1.207 mg/(mL*min) | Standard Deviation 0.409 |
| BCT197 High Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-10 | 1.263 mg/(mL*min) | Standard Deviation 0.4934 |
| BCT197 Low Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-3 | 1.111 mg/(mL*min) | Standard Deviation 0.4245 |
| BCT197 Low Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-7 | 1.143 mg/(mL*min) | Standard Deviation 0.4433 |
| BCT197 Low Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-10 | 1.174 mg/(mL*min) | Standard Deviation 0.438 |
| BCT197 Low Dose Regimen | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-14 | 1.192 mg/(mL*min) | Standard Deviation 0.4007 |
| Placebo | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-10 | 1.155 mg/(mL*min) | Standard Deviation 0.4061 |
| Placebo | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-7 | 1.108 mg/(mL*min) | Standard Deviation 0.398 |
| Placebo | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-3 | 1.097 mg/(mL*min) | Standard Deviation 0.3876 |
| Placebo | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population | Day 1-14 | 1.125 mg/(mL*min) | Standard Deviation 0.4293 |
Secondary
Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population
FEV1 data were recorded daily from Days 1 to 7, and Days 10 and 14 of the study using a computer-operated spirometer. Analysis was based on a linear MMRM with Change from Baseline in parameter as outcome; including treatment, visit, treatment by visit interaction, severity of airflow limitation at Baseline, blood eosinophils (%) at Baseline, time from start of current COPD exacerbation to first study treatment dosing, presence of cardiovascular comorbidities at Screening and COPD exacerbation treatment at Screening as fixed effects, and Baseline value and Baseline by visit interaction as covariates. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.
Time frame: Days 3, 10, and 14
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BCT197 High Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 14 | 0.047 litre | Standard Deviation 0.2627 |
| BCT197 High Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 10 | 0.095 litre | Standard Deviation 0.29 |
| BCT197 High Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 3 | 0.026 litre | Standard Deviation 0.2118 |
| BCT197 Low Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 14 | 0.056 litre | Standard Deviation 0.2782 |
| BCT197 Low Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 10 | 0.071 litre | Standard Deviation 0.1995 |
| BCT197 Low Dose Regimen | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 3 | 0.059 litre | Standard Deviation 0.2101 |
| Placebo | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 10 | 0.063 litre | Standard Deviation 0.2879 |
| Placebo | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 3 | 0.063 litre | Standard Deviation 0.2392 |
| Placebo | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population | Day 14 | 0.056 litre | Standard Deviation 0.267 |
Secondary
Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population
RR (breaths/min) was recorded over time during the acute exacerbation phase.
Time frame: Days 1 to 14
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BCT197 High Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 3 | -2.0 breaths/min |
| BCT197 High Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 7 | -3.0 breaths/min |
| BCT197 High Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 10 | -3.0 breaths/min |
| BCT197 High Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 14 | -3.0 breaths/min |
| BCT197 Low Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 14 | -2.0 breaths/min |
| BCT197 Low Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 3 | -1.0 breaths/min |
| BCT197 Low Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 10 | -2.0 breaths/min |
| BCT197 Low Dose Regimen | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 7 | -2.0 breaths/min |
| Placebo | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 14 | -3.0 breaths/min |
| Placebo | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 7 | -2.0 breaths/min |
| Placebo | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 10 | -2.0 breaths/min |
| Placebo | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population | Day 3 | -2.0 breaths/min |
Secondary
Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population
FEV1 and FVC were recorded daily from Days 1 to 7 and on Days 10 and 14 and Weeks 8, 12, and 26 of the study using a computer-operated spirometer. FEV1/FVC normalization was achieved if FEV1/FVC returned to a value ≥ 89% of the most recent FEV1/FVC value measured within the last 12 months outside an exacerbation (pre-study FEV1/FVC value). Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.
Time frame: Baseline to Week 26
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 50.0 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 54.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 53.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 53.7 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 51.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 54.8 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 49.4 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 57.3 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 51.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 51.8 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 53.8 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 52.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 51.7 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 48.2 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 47.0 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 47.8 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 46.3 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 50.0 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 50.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 43.8 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 48.8 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 53.3 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 47.4 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 47.1 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 51.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 55.4 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 50.6 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 51.9 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 48.8 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 51.9 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 51.2 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 46.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 47.6 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 51.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 51.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1/FVC Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 45.8 percentage of participants |
Secondary
Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population
FEV1 data were recorded daily from Days 1 to 7 and on Days 10 and 14 and Weeks 8, 12, and 26 of the study using a computer-operated spirometer. FEV1 normalization was achieved if FEV1 returned to a value ≥ 89% of the most recent FEV1 value measured within the last 12 months outside an exacerbation (pre-study FEV1 value). Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments. Percentages (%) were based on number of non-missing values as denominator.
Time frame: Baseline, Days 1 to 7, Days 10 and 14, Week 8, Week 12 and Week 26
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 62.7 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 75.7 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 77.2 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 70.5 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 71.6 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 76.8 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 67.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 61.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 74.0 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 67.5 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 71.1 percentage of participants |
| BCT197 High Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 69.1 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 67.1 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 65.2 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 59.3 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 62.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 65.9 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 70.2 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 70.5 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 71.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 65.9 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 61.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 65.4 percentage of participants |
| BCT197 Low Dose Regimen | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 63.0 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Baseline | 64.6 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 3 | 75.0 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 12 | 68.8 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 14 | 75.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 2 | 73.2 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 10 | 66.7 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 8 | 71.4 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 6 | 75.0 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 5 | 74.7 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Week 26 | 69.3 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 7 | 70.4 percentage of participants |
| Placebo | Normalization Evaluation of FEV1 Over Time (Days 1 to 7, Days 10 and 14, and Weeks 8, 12 and 26) Compared With the Most Recent Test Performed Within the Last 12 Months Outside an Exacerbation - ITT Population | Day 4 | 75.0 percentage of participants |
Secondary
Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population
RR was normalized when it returned to a baseline plateau level achieved after the acute COPD exacerbation during the Stabilization Phase. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.
Time frame: Day 1 to Day 14
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 7 | 51.2 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 4 | 37.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 2 | 28.7 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 6 | 44.8 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 5 | 41.4 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Baseline | 14.9 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 10 | 47.6 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 3 | 28.7 percentage of participants |
| BCT197 High Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 14 | 57.8 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Baseline | 20.4 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 6 | 48.4 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 2 | 26.9 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 3 | 39.8 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 4 | 45.1 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 5 | 52.7 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 7 | 51.6 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 10 | 60.4 percentage of participants |
| BCT197 Low Dose Regimen | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 14 | 52.3 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 3 | 29.4 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Baseline | 17.4 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 7 | 47.1 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 2 | 26.7 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 14 | 56.5 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 10 | 48.2 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 5 | 39.3 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 4 | 37.6 percentage of participants |
| Placebo | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population | Day 6 | 48.2 percentage of participants |
Secondary
Number of COPD-Related Deaths During the Study - ITT Population
Cumulative incidences of COPD-related deaths until Day 30/60/90/120/150/180 were obtained.
Time frame: Days 1 to 180
Population: ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 30 | 0 Participants |
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 180 | 1 Participants |
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 150 | 1 Participants |
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 60 | 0 Participants |
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 90 | 0 Participants |
| BCT197 High Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 120 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 90 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 120 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 30 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 60 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 180 | 0 Participants |
| BCT197 Low Dose Regimen | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 150 | 0 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 180 | 1 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 30 | 1 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 60 | 1 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 90 | 1 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 150 | 1 Participants |
| Placebo | Number of COPD-Related Deaths During the Study - ITT Population | Until Day 120 | 1 Participants |
Secondary
Percentage of Days With Intake of COPD Rescue Therapy - ITT Population
Participants completed the EXACT-PRO starting from Day 1 and recorded rescue medication use and any occurrences of COPD once a day (evening) in the diary. The percentage of days with intake of rescue medications was evaluated on the basis of the information recorded daily by the participant on the diaries. A day was considered with intake of rescue medications if the answer to the question How many puffs of rescue medication did you take since last evening? was\> 0.
Time frame: Baseline to Week 26
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BCT197 High Dose Regimen | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Acute Exacerbation Phase (Overall) | 73.28 percentage of days | Standard Deviation 32.721 |
| BCT197 High Dose Regimen | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Stabilization Phase (Overall) | 70.78 percentage of days | Standard Deviation 37.122 |
| BCT197 Low Dose Regimen | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Acute Exacerbation Phase (Overall) | 71.90 percentage of days | Standard Deviation 33.565 |
| BCT197 Low Dose Regimen | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Stabilization Phase (Overall) | 71.08 percentage of days | Standard Deviation 40.299 |
| Placebo | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Acute Exacerbation Phase (Overall) | 69.65 percentage of days | Standard Deviation 35.674 |
| Placebo | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population | Stabilization Phase (Overall) | 67.35 percentage of days | Standard Deviation 38.953 |
Secondary
Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population
Follow-up time per participant (years) was defined as (date of last contact - date of first study drug administration + 1)/ 365.25. Total follow-up time (years) = sum of individual participant follow-up times. Rate was calculated as total number of positively adjudicated exacerbations divided by the total follow-up time in years of the treatment group.
Time frame: Day 1 to End of Study (Day 180)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCT197 High Dose Regimen | Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population | 0.744 proportion of participants |
| BCT197 Low Dose Regimen | Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population | 0.921 proportion of participants |
| Placebo | Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population | 0.904 proportion of participants |
Secondary
Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population
Information regarding the participant's condition can be obtained through 3 domain scores embedded within the EXACT measure: Breathlessness, Cough & Sputum, and Chest Symptoms. These scores also range from 0 to 100 with higher scores indicating more severe symptoms.The standardized AUC of the EXACT-PRO were calculated from Day (a) to Day (b) using the trapezoidal rule.
Time frame: Days 1 to 29
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 45.417 mg/(mL*min) |
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 50.083 mg/(mL*min) |
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 44.911 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 45.577 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 47.861 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 45.315 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 47.556 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 43.387 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 44.436 mg/(mL*min) |
Secondary
Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population
The standardized AUC of the EXACT-PRO were calculated from Day (a) to Day (b) using the trapezoidal rule.
Time frame: Days 1 to 29
Population: ITT Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 45.389 mg/(mL*min) |
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 41.470 mg/(mL*min) |
| BCT197 High Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 42.641 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 42.250 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 44.736 mg/(mL*min) |
| BCT197 Low Dose Regimen | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 40.932 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-7 | 43.938 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-29 | 41.652 mg/(mL*min) |
| Placebo | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population | Day 1-14 | 42.590 mg/(mL*min) |
Secondary
Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population
Time from hospitalization admission until the participant is medically ready for discharge (in days) = Date participant was medically ready for discharge from hospital - Date of hospitalization admission. Date of hospitalization admission' and 'Date participant was medically ready for discharge from hospital' were recorded on the 'Current COPD Exacerbation' form of the eCRF. Results were presented with 75th percentile (95% CI) due to the fact that 95% CI for the median was not evaluable.
Time frame: Day 1 to Day 30
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCT197 High Dose Regimen | Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population | 9.0 days |
| BCT197 Low Dose Regimen | Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population | 9.0 days |
| Placebo | Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population | 9.0 days |
Secondary
Time to Improvement Based on the EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome (EXACT-PRO) Total Score During the Acute Exacerbation Phase - ITT Population
Improvement based on EXACT-PRO total score is defined as a decrease in the Rolling Average EXACT score ≥ 9 points from the previous day's maximum observed value during an event. The EXACT is a 14-item patient reported outcome (PRO) daily diary used to quantify and measure exacerbations of COPD. The health status of the participant is correlated to the global score, meaning a higher score corresponds to a more severe health status of the participant. An EXACT Total score is computed for each day of diary collection. The EXACT Total score is based on a logit scoring system with conversion to a 0 to 100 scale for ease of interpretation and use. The total score was used in the determination of exacerbation frequency, severity and duration of exacerbation. Specifically, changes in the total score were used to define onset and recovery from an exacerbation event and the magnitude of that event.
Time frame: Days 1 to 29
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCT197 High Dose Regimen | Time to Improvement Based on the EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome (EXACT-PRO) Total Score During the Acute Exacerbation Phase - ITT Population | 5.0 days |
| BCT197 Low Dose Regimen | Time to Improvement Based on the EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome (EXACT-PRO) Total Score During the Acute Exacerbation Phase - ITT Population | 6.0 days |
| Placebo | Time to Improvement Based on the EXAcerbations of Chronic Pulmonary Disease Tool-Patient Reported Outcome (EXACT-PRO) Total Score During the Acute Exacerbation Phase - ITT Population | 5.0 days |
p-value: 0.72Log Rank
p-value: 0.298Log Rank
p-value: 0.47Log Rank
Secondary
Time to Improvement of 100 mL in FEV1 Over Time - ITT Population
Time to improvement of 100 mL in FEV1 was defined as time (in days) from initiation of study treatment until the change in FEV1 was ≥ +100 mL.
Time frame: Baseline to Week 26
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCT197 High Dose Regimen | Time to Improvement of 100 mL in FEV1 Over Time - ITT Population | 3.0 days |
| BCT197 Low Dose Regimen | Time to Improvement of 100 mL in FEV1 Over Time - ITT Population | 2.0 days |
| Placebo | Time to Improvement of 100 mL in FEV1 Over Time - ITT Population | 4.0 days |
p-value: 0.399Log Rank
p-value: 0.091Log Rank
p-value: 0.437Log Rank
Secondary
Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population
Time to next positively adjudicated moderate/severe COPD exacerbation (in days) was defined as date when first moderate/severe COPD exacerbation symptoms started - date when current COPD exacerbation symptoms stopped, where COPD exacerbations experienced during the study were positively adjudicated by the Independent Adjudication Committee. Time to next positively adjudicated COPD exacerbation was presented in 25th percentile (95% confidence interval) as medians were not evaluable.
Time frame: Day 1 to Day 180
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCT197 High Dose Regimen | Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population | 168.0 days |
| BCT197 Low Dose Regimen | Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population | 75.0 days |
| Placebo | Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population | 143.0 days |
Secondary
Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population
Recovery based on EXACT-PRO total score was defined as the first day in which a participant experiences a persistent, sustained improvement in their condition over the observed period (Day 1 to Day 29). Improvement had to be present for 7 consecutive days. The first day of the 7-day period was designated as the first day of Recovery. An EXACT total score was computed for each day of diary collection.
Time frame: Days 1 to 29
Population: ITT Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BCT197 High Dose Regimen | Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population | 6.0 days |
| BCT197 Low Dose Regimen | Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population | 6.0 days |
| Placebo | Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population | 6.0 days |
Other Pre-specified
Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population
Descriptive summary of PK plasma concentration is presented as no-specific PK report is available.
Time frame: Days 1 to 5
Population: PK Population: all participants who received at least one dose administration and had at least one quantifiable plasma concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (pre-dose) | 271.10 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (>12h post-dose) | 466.86 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (>12h post-dose) | 413.85 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (pre-dose) | 272.43 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (0-2h post-dose) | 318.88 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (0-2h post-dose) | 310.20 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (4-8h post dose) | 387.65 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (4-8h post-dose) | 504.53 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (4-8h post-dose) | 496.31 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (>12h post-dose) | 465.28 ng/mL |
| BCT197 High Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (0-2 h post-dose) | 97.40 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (>12h post-dose) | 240.31 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (0-2 h post-dose) | 75.98 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (4-8h post dose) | 283.79 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 1 (>12h post-dose) | 286.40 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (pre-dose) | 161.13 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (0-2h post-dose) | 184.46 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (4-8h post-dose) | 299.79 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 3 (>12h post-dose) | 249.60 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (pre-dose) | 128.38 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (0-2h post-dose) | 155.10 ng/mL |
| BCT197 Low Dose Regimen | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population | Day 5 (4-8h post-dose) | 278.73 ng/mL |