Efficacy and Safety of BCT197 in Subjects With Acute Resp... | NCT02700919

Label	Type	Description	Intervention Names
Regimen 1	Experimental	Drug: BCT197 Dose 1, Day 1 to Day 5	Drug: BCT197
Regimen 2	Experimental	Drug: BCT197 Dose 2, Day 1 to Day 5	Drug: BCT197
Regimen 3	Placebo Comparator	Placebo Day 1 to Day 5	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
BCT197	Drug	Capsules will be taken orally with fluids over a 5 day period after randomization	Regimen 1 Regimen 2

Measure	Description	Time Frame
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).	Days 1 to 7

Measure	Description	Time Frame
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.

Measure	Description	Time Frame
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.	Days 1 to 5

Name	Affiliation	Role
Jacqueline Parkin, PhD FRCP	Mereo BioPharma	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mereo Research Site		Michigan City	Indiana		United States
Mereo Research Site

ID	Title	Description
FG000	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.
FG001	BCT197 Low Dose Regimen

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 8, 2016	Sep 8, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

ITT Population

Posted

Mean

95% Confidence Interval

litre

Days 1 to 7

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Units	Counts
Participants	OG00087 OG00193 OG00286

Title

Denominators

Categories

Title	Measurements
	OG0000.084(0.019 to 0.149) OG0010.115(0.049 to 0.180) OG0020.057(-0.011 to 0.125)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	Change from Baseline on Day 7	Log Rank		0.012														Superiority
OG001	Change from Baseline on Day 7	Log Rank		<0.001

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.

ITT Population

Posted

Mean

Standard Deviation

litre

Days 3, 10, and 14

ID	Title	Description
OG000	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.
OG001	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.

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.

ITT Population

Posted

Number

percentage of participants

Baseline, Days 1 to 7, Days 10 and 14, Week 8, Week 12 and Week 26

ID	Title	Description
OG000	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.
OG001	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.

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.

ITT Population

Posted

Number

percentage of participants

Baseline to Week 26

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

ITT Population

Posted

Median

95% Confidence Interval

days

Baseline to Week 26

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Mean

Standard Deviation

mg/(mL*min)

Day 1 to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo

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.

ITT Population

Posted

Number

percentage of participants

Day 1 to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Median

Full Range

breaths/min

Days 1 to 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Median

95% Confidence Interval

days

Days 1 to 29

ID	Title	Description
OG000	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.
OG001	BCT197 Low Dose Regimen

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.

ITT Population

Posted

Median

95% Confidence Interval

days

Days 1 to 29

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Median

Full Range

mg/(mL*min)

Days 1 to 29

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Median

Full Range

mg/(mL*min)

Days 1 to 29

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Number

proportion of participants

Day 1 to End of Study (Day 180)

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Count of Participants

Participants

Days 1 to 180

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

ITT Population

Posted

Median

95% Confidence Interval

days

Day 1 to Day 180

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo

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.

ITT Population

Posted

Median

95% Confidence Interval

days

Day 1 to Day 30

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo

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.

ITT Population

Posted

Mean

Standard Deviation

percentage of days

Baseline to Week 26

ID	Title	Description
OG000	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.
OG001	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.
OG002	Placebo

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.

PK Population: all participants who received at least one dose administration and had at least one quantifiable plasma concentration.

Posted

Geometric Mean

95% Confidence Interval

ng/mL

Days 1 to 5

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Lymphadenopathy mediastinal	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Lymphocytosis	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Angina pectoris	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Angina unstable	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected96 at risk EG0020 events0 affected91 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0012 events2 affected96 at risk EG0021 events1 affected91 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Bundle branch block left	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Cardiac aneurysm	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0012 events2 affected96 at risk EG0022 events2 affected91 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Cor pulmonale	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Intracardiac thrombus	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Right ventricular failure	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected96 at risk EG0020 events0 affected91 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Tachycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0022 events2 affected91 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0022 events1 affected91 at risk
Chalazion	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Retinal vein occlusion	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Scleral hyperaemia	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Vitreous detachment	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Abdominal wall haematoma	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0024 events4 affected91 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0016 events4 affected96 at risk EG0020 events0 affected91 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Asthenia	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0023 events3 affected91 at risk
Chest discomfort	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Chest pain	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Chills	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Death	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Acarodermatitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Chronic sinusitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Conjunctivitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Cystitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Herpes zoster	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Laryngitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Mastoiditis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0004 events4 affected92 at risk EG0014 events4 affected96 at risk EG0022 events2 affected91 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Oral herpes	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0013 events3 affected96 at risk EG0022 events2 affected91 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0013 events3 affected96 at risk EG0020 events0 affected91 at risk
Sepsis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events1 affected91 at risk
Sinusitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Viral infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Animal bite	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Tendon injury	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0014 events3 affected96 at risk EG0022 events2 affected91 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0015 events4 affected96 at risk EG0021 events1 affected91 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0014 events2 affected96 at risk EG0020 events0 affected91 at risk
Blood glucose increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Blood phosphorus decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Blood potassium increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Blood pressure increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Blood urea increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Blood uric acid increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0013 events3 affected96 at risk EG0020 events0 affected91 at risk
Gamma-glutamyltransferase abnormal	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0012 events2 affected96 at risk EG0021 events1 affected91 at risk
Haemoglobin decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Hepatic enzyme increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
International normalised ratio increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Monocyte count increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Platelet count increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Protein total decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Prothrombin time prolonged	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Troponin I increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Weight decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Dyslipidaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0014 events4 affected96 at risk EG0023 events2 affected91 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events1 affected92 at risk EG0013 events2 affected96 at risk EG0021 events1 affected91 at risk
Hypochloraemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Bone swelling	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Adrenal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Laryngeal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Phaeochromocytoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Apallic syndrome	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Arachnoid cyst	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Brain oedema	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Coma	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Epilepsy	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Headache	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Hypotonia	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Hypoxic-ischaemic encephalopathy	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Syncope	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Tremor	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0004 events3 affected92 at risk EG0012 events2 affected96 at risk EG0020 events0 affected91 at risk
Anxiety	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected96 at risk EG0020 events0 affected91 at risk
Depression	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Dysphoria	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Insomnia	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Sleep disorder	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Diabetic nephropathy	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Dysuria	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0012 events1 affected96 at risk EG0020 events0 affected91 at risk
Haematuria	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Renal artery stenosis	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Renal colic	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Renal cyst	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Vulvovaginal inflammation	Reproductive system and breast disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG00033 events24 affected92 at risk EG00142 events32 affected96 at risk EG00241 events28 affected91 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected92 at risk EG0012 events2 affected96 at risk EG0025 events4 affected91 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Paranasal cyst	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Pleural thickening	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Rales	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0012 events2 affected96 at risk EG0023 events3 affected91 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Tonsillar erythema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Upper respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Cataract operation	Surgical and medical procedures	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Aortic aneurysm	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Aortic arteriosclerosis	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Circulatory collapse	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Hypertension	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0005 events4 affected92 at risk EG0012 events2 affected96 at risk EG0024 events4 affected91 at risk
Hypertensive crisis	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0022 events2 affected91 at risk
Extravasation	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Generalised oedema	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Malaise	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Oedema peripheral	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Peripheral swelling	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0012 events2 affected96 at risk EG0020 events0 affected91 at risk
Pyrexia	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0020 events0 affected91 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0011 events1 affected96 at risk EG0021 events1 affected91 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Liver injury	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk
Non-alcoholic fatty liver	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected92 at risk EG0010 events0 affected96 at risk EG0020 events0 affected91 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected92 at risk EG0010 events0 affected96 at risk EG0021 events1 affected91 at risk

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	2	92	17	92	56	92
EG001	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.	3	96	27	96	63	96
EG002	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.	2	91	29	91	62	91