Efficacy and Safety of BCT197 in Subjects With Acute Respiratory Exacerbations of Chronic Obstructive Pulmonary Disease
Sponsor
Mereo BioPharma (Industry)
Overall Status
Completed
CT.gov ID
NCT02700919
Collaborator
(none)
282
46
3
15.9
6.1
0.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
282 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II, Two-Part, Randomised, Multi-Centre, Multinational, Double-Blind, Placebo-Controlled, Parallel Group Study to Compare the Efficacy and Safety of BCT197 When Added on to Standard of Care for the Treatment of Acute Respiratory Exacerbations of Chronic Obstructive Pulmonary Disease Requiring Hospitalisation in Adults
Actual Study Start Date
:
Aug 1, 2016
Actual Primary Completion Date
:
Nov 8, 2017
Actual Study Completion Date
:
Nov 28, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regimen 1 Drug: BCT197 Dose 1, Day 1 to Day 5 |
Drug: BCT197
Capsules will be taken orally with fluids over a 5 day period after randomization
|
| Experimental: Regimen 2 Drug: BCT197 Dose 2, Day 1 to Day 5 |
Drug: BCT197
Capsules will be taken orally with fluids over a 5 day period after randomization
|
| Placebo Comparator: Regimen 3 Placebo Day 1 to Day 5 |
Drug: Placebo
Capsules will be taken orally with fluids over a 5 day period after randomization
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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.
- 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.
- 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.
- 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.
Other Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mereo Research Site | Michigan City | Indiana | United States | |
| 2 | Mereo Research Site | Baltimore | Maryland | United States | |
| 3 | Mereo Research Site | Milwaukee | Wisconsin | United States | |
| 4 | Mereo Research Site | Dupnitsa | Bulgaria | ||
| 5 | Mereo Research Site | Gabrovo | Bulgaria | ||
| 6 | Mereo Research Site | Kardzhali | Bulgaria | ||
| 7 | Mereo Research Site | Kozloduy | Bulgaria | ||
| 8 | Mereo Research Site | Kyustendil | Bulgaria | ||
| 9 | Mereo Research Site | Lovech | Bulgaria | ||
| 10 | Mereo Research Site | Montana | Bulgaria | ||
| 11 | Mereo Research Site | Razgrad | Bulgaria | ||
| 12 | Mereo Research Site | Ruse | Bulgaria | ||
| 13 | Mereo Research Site | Shumen | Bulgaria | ||
| 14 | Mereo Research Site | Sliven | Bulgaria | ||
| 15 | Mereo Research Site | Sofia | Bulgaria | ||
| 16 | Mereo Research Site | Kyjov | Czechia | ||
| 17 | Mereo Research Site | Melnik | Czechia | ||
| 18 | Mereo Research Site | Slany | Czechia | ||
| 19 | Mereo Research Site | Dresden | Germany | ||
| 20 | Mereo Research Site | Balassagyarmat | Hungary | ||
| 21 | Mereo Research Site | Budapest | Hungary | ||
| 22 | Mereo Research Site | Debrecen | Hungary | ||
| 23 | Mereo Research Site | Farkasgyepu | Hungary | ||
| 24 | Mereo Research Site | Miskolc | Hungary | ||
| 25 | Mereo Research Site | Mohacs | Hungary | ||
| 26 | Mereo Research Site | Naples | Italy | ||
| 27 | Mereo Research Site | Daugavpils | Latvia | ||
| 28 | Mereo Research Site | Riga | Latvia | ||
| 29 | Mereo Research Site | Valmiera | Latvia | ||
| 30 | Mereo Research Site | Chrzanow | Poland | ||
| 31 | Mereo Research Site | Krakow | Poland | ||
| 32 | Mereo Research Site | Proszowice | Poland | ||
| 33 | Mereo Research Site | Wroclaw | Poland | ||
| 34 | Mereo Research Site | Zgierz | Poland | ||
| 35 | Mereo Research Site | Bucharest | Romania | ||
| 36 | Mereo Research Site | Cluj Napoca | Romania | ||
| 37 | Mereo Research Site | Constanta | Romania | ||
| 38 | Mereo Research Site | Craiova | Romania | ||
| 39 | Mereo Research Site | Marghita | Romania | ||
| 40 | Mereo Research Site | Suceava | Romania | ||
| 41 | Mereo Research Site | Timisoara | Romania | ||
| 42 | Mereo Research Site | Izhevsk | Russian Federation | ||
| 43 | Mereo Research Site | Kemerovo | Russian Federation | ||
| 44 | Mereo Research Site | Saint Petersburg | Russian Federation | ||
| 45 | Mereo Research Site | Saratov | Russian Federation | ||
| 46 | Mereo Research Site | Tomsk | Russian Federation |
Sponsors and Collaborators
- Mereo BioPharma
Investigators
- Study Director: Jacqueline Parkin, PhD FRCP, Mereo BioPharma
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Mereo BioPharma
ClinicalTrials.gov Identifier:
NCT02700919
Other Study ID Numbers:
- MBCT206
First Posted:
Mar 7, 2016
Last Update Posted:
Nov 30, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Period Title: Overall Study | |||
| STARTED | 94 | 97 | 91 |
| COMPLETED | 82 | 85 | 87 |
| NOT COMPLETED | 12 | 12 | 4 |
Baseline Characteristics
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 87 | 93 | 86 | 266 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
63.8
(8.34)
|
63.1
(8.68)
|
64.7
(7.06)
|
63.8
(8.07)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
21
24.1%
|
26
28%
|
27
31.4%
|
74
27.8%
|
| Male |
66
75.9%
|
67
72%
|
59
68.6%
|
192
72.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
0
0%
|
1
1.1%
|
0
0%
|
1
0.4%
|
| White |
87
100%
|
92
98.9%
|
85
98.8%
|
264
99.2%
|
| Other |
0
0%
|
0
0%
|
1
1.2%
|
1
0.4%
|
| FEV1 at Screening (litre) [Mean (Standard Deviation) ] | ||||
| Pre-bronchodilator |
0.875
(0.3649)
|
0.871
(0.3091)
|
0.921
(0.2775)
|
0.887
(0.3166)
|
| Post-bronchodilator |
1.135
(0.3875)
|
1.046
(0.4009)
|
1.033
(0.3558)
|
1.071
(0.3836)
|
| Forced Vital Capacity (FVC) at Screening (litre) [Mean (Standard Deviation) ] | ||||
| Pre-bronchodilator |
2.410
(0.8883)
|
2.137
(0.8675)
|
2.352
(0.7623)
|
2.293
(0.8416)
|
| Post-bronchodilator |
2.619
(0.8167)
|
2.514
(0.8488)
|
2.427
(0.7298)
|
2.521
(0.8022)
|
| FEV1/FVC at Screening (Ratio) [Mean (Standard Deviation) ] | ||||
| Pre-bronchodilator |
0.381
(0.1109)
|
0.424
(0.0982)
|
0.404
(0.0972)
|
0.403
(0.1025)
|
| Post-bronchodilator |
0.447
(0.1245)
|
0.427
(0.1107)
|
0.436
(0.1184)
|
0.436
(0.1177)
|
Outcome Measures
| Title | Change From Baseline in FEV1 to Day 7 - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Mean (95% Confidence Interval) [litre] |
0.084
|
0.115
|
0.057
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen |
|---|---|---|
| Comments | Change from Baseline on Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BCT197 Low Dose Regimen |
|---|---|---|
| Comments | Change from Baseline on Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo |
|---|---|---|
| Comments | Change from Baseline on Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.102 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, Placebo |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.507 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.027 | |
| Confidence Interval |
(2-Sided) 95% -0.053 to 0.107 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | BCT197 Low Dose Regimen, Placebo |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.148 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.058 | |
| Confidence Interval |
(2-Sided) 95% -0.021 to 0.136 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, BCT197 Low Dose Regimen |
|---|---|---|
| Comments | Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.443 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.031 | |
| Confidence Interval |
(2-Sided) 95% -0.109 to 0.048 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in FEV1 on Days 3, 10, and 14 - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Day 3 |
0.026
(0.2118)
|
0.059
(0.2101)
|
0.063
(0.2392)
|
| Day 10 |
0.095
(0.2900)
|
0.071
(0.1995)
|
0.063
(0.2879)
|
| Day 14 |
0.047
(0.2627)
|
0.056
(0.2782)
|
0.056
(0.2670)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Baseline |
67.9
78%
|
59.3
63.8%
|
64.6
75.1%
|
| Day 2 |
61.9
71.1%
|
65.2
70.1%
|
73.2
85.1%
|
| Day 3 |
67.5
77.6%
|
62.6
67.3%
|
75.0
87.2%
|
| Day 4 |
62.7
72.1%
|
65.9
70.9%
|
75.0
87.2%
|
| Day 5 |
71.1
81.7%
|
70.2
75.5%
|
74.7
86.9%
|
| Day 6 |
76.8
88.3%
|
70.5
75.8%
|
75.0
87.2%
|
| Day 7 |
71.6
82.3%
|
71.6
77%
|
70.4
81.9%
|
| Day 10 |
77.2
88.7%
|
65.9
70.9%
|
66.7
77.6%
|
| Day 14 |
69.1
79.4%
|
61.6
66.2%
|
75.3
87.6%
|
| Week 8 |
74.0
85.1%
|
65.4
70.3%
|
71.4
83%
|
| Week 12 |
70.5
81%
|
63.0
67.7%
|
68.8
80%
|
| Week 26 |
75.7
87%
|
67.1
72.2%
|
69.3
80.6%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Baseline |
49.4
56.8%
|
47.8
51.4%
|
45.8
53.3%
|
| Day 2 |
51.8
59.5%
|
50.0
53.8%
|
55.4
64.4%
|
| Day 3 |
54.9
63.1%
|
53.3
57.3%
|
50.6
58.8%
|
| Day 4 |
53.7
61.7%
|
48.8
52.5%
|
51.9
60.3%
|
| Day 5 |
57.3
65.9%
|
47.0
50.5%
|
48.8
56.7%
|
| Day 6 |
51.9
59.7%
|
50.6
54.4%
|
51.9
60.3%
|
| Day 7 |
53.8
61.8%
|
51.7
55.6%
|
51.2
59.5%
|
| Day 10 |
52.6
60.5%
|
47.1
50.6%
|
46.3
53.8%
|
| Day 14 |
50.0
57.5%
|
48.2
51.8%
|
47.6
55.3%
|
| Week 8 |
53.9
62%
|
46.3
49.8%
|
51.3
59.7%
|
| Week 12 |
51.9
59.7%
|
43.8
47.1%
|
51.3
59.7%
|
| Week 26 |
54.8
63%
|
47.4
51%
|
51.3
59.7%
|
| Title | Time to Improvement of 100 mL in FEV1 Over Time - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Median (95% Confidence Interval) [days] |
3.0
|
2.0
|
4.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.399 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BCT197 Low Dose Regimen, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.091 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, BCT197 Low Dose Regimen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.437 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Area Under the Curve (AUC) of FEV1 Over Time - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Day 1-3 |
1.207
(0.4090)
|
1.111
(0.4245)
|
1.097
(0.3876)
|
| Day 1-7 |
1.232
(0.4296)
|
1.143
(0.4433)
|
1.108
(0.3980)
|
| Day 1-10 |
1.263
(0.4934)
|
1.174
(0.4380)
|
1.155
(0.4061)
|
| Day 1-14 |
1.293
(0.4743)
|
1.192
(0.4007)
|
1.125
(0.4293)
|
| Title | Normalization of Respiratory Rate (RR) Over Time During Acute Exacerbation Phase - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Baseline |
14.9
17.1%
|
20.4
21.9%
|
17.4
20.2%
|
| Day 2 |
28.7
33%
|
26.9
28.9%
|
26.7
31%
|
| Day 3 |
28.7
33%
|
39.8
42.8%
|
29.4
34.2%
|
| Day 4 |
37.9
43.6%
|
45.1
48.5%
|
37.6
43.7%
|
| Day 5 |
41.4
47.6%
|
52.7
56.7%
|
39.3
45.7%
|
| Day 6 |
44.8
51.5%
|
48.4
52%
|
48.2
56%
|
| Day 7 |
51.2
58.9%
|
51.6
55.5%
|
47.1
54.8%
|
| Day 10 |
47.6
54.7%
|
60.4
64.9%
|
48.2
56%
|
| Day 14 |
57.8
66.4%
|
52.3
56.2%
|
56.5
65.7%
|
| Title | Change From Baseline in RR on Days 3, 7, 10 and 14 - ITT Population |
|---|---|
| Description | RR (breaths/min) was recorded over time during the acute exacerbation phase. |
| Time Frame | Days 1 to 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Day 3 |
-2.0
|
-1.0
|
-2.0
|
| Day 7 |
-3.0
|
-2.0
|
-2.0
|
| Day 10 |
-3.0
|
-2.0
|
-2.0
|
| Day 14 |
-3.0
|
-2.0
|
-3.0
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Median (95% Confidence Interval) [days] |
5.0
|
6.0
|
5.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.720 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BCT197 Low Dose Regimen, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.298 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | BCT197 High Dose Regimen, BCT197 Low Dose Regimen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.470 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Time to Recovery Based on EXACT-PRO Total Score During the Acute Exacerbation Phase - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Median (95% Confidence Interval) [days] |
6.0
|
6.0
|
6.0
|
| Title | Standardized AUC of EXACT-PRO Rolling Average Over Time During Acute Exacerbation Phase - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Day 1-7 |
45.389
|
44.736
|
43.938
|
| Day 1-14 |
42.641
|
42.250
|
42.590
|
| Day 1-29 |
41.470
|
40.932
|
41.652
|
| Title | Standardized AUC of EXACT-PRO (Breathlessness) Rolling Average Over Time During Acute Exacerbation Phase - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Day 1-7 |
50.083
|
47.861
|
47.556
|
| Day 1-14 |
45.417
|
45.577
|
44.436
|
| Day 1-29 |
44.911
|
45.315
|
43.387
|
| Title | Rate of Positively Adjudicated Moderate/Severe COPD Exacerbations - ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Number [proportion of participants] |
0.744
0.9%
|
0.921
1%
|
0.904
1.1%
|
| Title | Number of COPD-Related Deaths During the Study - ITT Population |
|---|---|
| Description | Cumulative incidences of COPD-related deaths until Day 30/60/90/120/150/180 were obtained. |
| Time Frame | Days 1 to 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Until Day 30 |
0
0%
|
0
0%
|
1
1.2%
|
| Until Day 60 |
0
0%
|
0
0%
|
1
1.2%
|
| Until Day 90 |
0
0%
|
0
0%
|
1
1.2%
|
| Until Day 120 |
0
0%
|
0
0%
|
1
1.2%
|
| Until Day 150 |
1
1.1%
|
0
0%
|
1
1.2%
|
| Until Day 180 |
1
1.1%
|
0
0%
|
1
1.2%
|
| Title | Time to Next Positively Adjudicated Moderate/Severe COPD Exacerbation- ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Median (95% Confidence Interval) [days] |
168.0
|
75.0
|
143.0
|
| Title | Time From Hospitalization Admission Until the Participant Is Medically Ready for Discharge (Current COPD) - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Median (95% Confidence Interval) [days] |
9.0
|
9.0
|
9.0
|
| Title | Percentage of Days With Intake of COPD Rescue Therapy - ITT Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 87 | 93 | 86 |
| Acute Exacerbation Phase (Overall) |
73.28
(32.721)
|
71.90
(33.565)
|
69.65
(35.674)
|
| Stabilization Phase (Overall) |
70.78
(37.122)
|
71.08
(40.299)
|
67.35
(38.953)
|
| Title | Pharmacokinetic (PK) of BCT197 in Adults With COPD - PK Population |
|---|---|
| Description | Descriptive summary of PK plasma concentration is presented as no-specific PK report is available. |
| Time Frame | Days 1 to 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: all participants who received at least one dose administration and had at least one quantifiable plasma concentration. |
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 92 | 92 |
| Day 1 (0-2 h post-dose) |
97.40
|
75.98
|
| Day 1 (4-8h post dose) |
387.65
|
283.79
|
| Day 1 (>12h post-dose) |
413.85
|
286.40
|
| Day 3 (pre-dose) |
271.10
|
161.13
|
| Day 3 (0-2h post-dose) |
318.88
|
184.46
|
| Day 3 (4-8h post-dose) |
496.31
|
299.79
|
| Day 3 (>12h post-dose) |
466.86
|
249.60
|
| Day 5 (pre-dose) |
272.43
|
128.38
|
| Day 5 (0-2h post-dose) |
310.20
|
155.10
|
| Day 5 (4-8h post-dose) |
504.53
|
278.73
|
| Day 5 (>12h post-dose) |
465.28
|
240.31
|
Adverse Events
| Time Frame | Adverse events (AEs) were recorded from signing the informed consent form to completion of the 26 week follow-up period after the last administration of study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Serious AEs are also included in the non-serious AE section as a non-serious AE table was not available. The difference in numbers between the participant flow module and safety population is because some participants were randomized but did not go on to receive at least one dose of study medication. | |||||
| Arm/Group Title | BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | |||
| Arm/Group Description | 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. | 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. | 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. | |||
All Cause Mortality |
||||||
| BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/92 (2.2%) | 3/96 (3.1%) | 2/91 (2.2%) | |||
Serious Adverse Events |
||||||
| BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/92 (18.5%) | 27/96 (28.1%) | 29/91 (31.9%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Angina unstable | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Atrial fibrillation | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Cardiac failure congestive | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Cardiopulmonary failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Right ventricular failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal wall haematoma | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| General disorders | ||||||
| Death | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Generalised oedema | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hepatobiliary disorders | ||||||
| Drug-induced liver injury | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Infections and infestations | ||||||
| Chronic sinusitis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Gastroenteritis viral | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Infection | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Pneumonia | 1/92 (1.1%) | 1 | 3/96 (3.1%) | 3 | 2/91 (2.2%) | 2 |
| Viral infection | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Diabetes mellitus | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hyperkalaemia | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Laryngeal cancer | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Nervous system disorders | ||||||
| Apallic syndrome | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Bronchiectasis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Chronic obstructive pulmonary disease | 13/92 (14.1%) | 14 | 21/96 (21.9%) | 28 | 22/91 (24.2%) | 25 |
| Chronic respiratory failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Dyspnoea | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Pulmonary embolism | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Pulmonary fibrosis | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Respiratory failure | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 3/91 (3.3%) | 3 |
Other (Not Including Serious) Adverse Events |
||||||
| BCT197 High Dose Regimen | BCT197 Low Dose Regimen | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 56/92 (60.9%) | 63/96 (65.6%) | 62/91 (68.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Iron deficiency anaemia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Leukocytosis | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Leukopenia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Lymphadenopathy mediastinal | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Lymphocytosis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Lymphopenia | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Neutropenia | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Thrombocytosis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Cardiac disorders | ||||||
| Angina pectoris | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Angina unstable | 0/92 (0%) | 0 | 2/96 (2.1%) | 2 | 0/91 (0%) | 0 |
| Atrial fibrillation | 3/92 (3.3%) | 3 | 2/96 (2.1%) | 2 | 1/91 (1.1%) | 1 |
| Atrial tachycardia | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Bundle branch block left | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Cardiac aneurysm | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Cardiac failure | 1/92 (1.1%) | 1 | 2/96 (2.1%) | 2 | 2/91 (2.2%) | 2 |
| Cardiac failure acute | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Cardiac failure chronic | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Cardiac failure congestive | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Cardiopulmonary failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Cor pulmonale | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Intracardiac thrombus | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Left ventricular hypertrophy | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Myocardial ischaemia | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Right ventricular failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Sinus bradycardia | 0/92 (0%) | 0 | 2/96 (2.1%) | 2 | 0/91 (0%) | 0 |
| Sinus tachycardia | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Supraventricular extrasystoles | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Tachyarrhythmia | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Tachycardia | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Ventricular extrasystoles | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 2/91 (2.2%) | 2 |
| Ventricular tachycardia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 2 |
| Eye disorders | ||||||
| Chalazion | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Retinal vein occlusion | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Scleral hyperaemia | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Vitreous detachment | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Abdominal pain upper | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Abdominal wall haematoma | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Constipation | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Diarrhoea | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 4/91 (4.4%) | 4 |
| Dyspepsia | 0/92 (0%) | 0 | 4/96 (4.2%) | 6 | 0/91 (0%) | 0 |
| Gastric polyps | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Gastritis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Gastrooesophageal reflux disease | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Pancreatitis chronic | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| General disorders | ||||||
| Asthenia | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 3/91 (3.3%) | 3 |
| Chest discomfort | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Chest pain | 2/92 (2.2%) | 2 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Chills | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Death | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Extravasation | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Generalised oedema | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Malaise | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Oedema peripheral | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Peripheral swelling | 0/92 (0%) | 0 | 2/96 (2.1%) | 2 | 0/91 (0%) | 0 |
| Pyrexia | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholangitis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Cholecystitis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Cholelithiasis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Hepatic steatosis | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Hyperbilirubinaemia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Liver injury | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Non-alcoholic fatty liver | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Drug-induced liver injury | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Infections and infestations | ||||||
| Acarodermatitis | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Chronic sinusitis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Conjunctivitis | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Cystitis | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Gastroenteritis viral | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Herpes zoster | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Infection | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Laryngitis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Lower respiratory tract infection | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Mastoiditis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Nasopharyngitis | 4/92 (4.3%) | 4 | 4/96 (4.2%) | 4 | 2/91 (2.2%) | 2 |
| Oesophageal candidiasis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Oral herpes | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Pneumonia | 3/92 (3.3%) | 3 | 3/96 (3.1%) | 3 | 2/91 (2.2%) | 2 |
| Respiratory tract infection | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Respiratory tract infection viral | 3/92 (3.3%) | 3 | 3/96 (3.1%) | 3 | 0/91 (0%) | 0 |
| Sepsis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 2 |
| Sinusitis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Upper respiratory tract infection | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Viral infection | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Viral upper respiratory tract infection | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Animal bite | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Contusion | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Fall | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Hand fracture | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Ligament sprain | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Limb injury | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Tendon injury | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Upper limb fracture | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Investigations | ||||||
| Alanine aminotransferase increased | 3/92 (3.3%) | 3 | 3/96 (3.1%) | 4 | 2/91 (2.2%) | 2 |
| Aspartate aminotransferase increased | 1/92 (1.1%) | 1 | 4/96 (4.2%) | 5 | 1/91 (1.1%) | 1 |
| Blood creatinine increased | 0/92 (0%) | 0 | 2/96 (2.1%) | 4 | 0/91 (0%) | 0 |
| Blood glucose increased | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Blood phosphorus decreased | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Blood potassium increased | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Blood pressure increased | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Blood urea increased | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Blood uric acid increased | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Creatinine renal clearance decreased | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Electrocardiogram QT prolonged | 0/92 (0%) | 0 | 3/96 (3.1%) | 3 | 0/91 (0%) | 0 |
| Gamma-glutamyltransferase abnormal | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Gamma-glutamyltransferase increased | 2/92 (2.2%) | 2 | 2/96 (2.1%) | 2 | 1/91 (1.1%) | 1 |
| Haemoglobin decreased | 1/92 (1.1%) | 2 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Hepatic enzyme increased | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| International normalised ratio increased | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Monocyte count increased | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Platelet count increased | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Protein total decreased | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Prothrombin time prolonged | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Troponin I increased | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Weight decreased | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Dehydration | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Diabetes mellitus | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Dyslipidaemia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Glucose tolerance impaired | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Hyperglycaemia | 2/92 (2.2%) | 2 | 4/96 (4.2%) | 4 | 2/91 (2.2%) | 3 |
| Hyperkalaemia | 1/92 (1.1%) | 2 | 2/96 (2.1%) | 3 | 1/91 (1.1%) | 1 |
| Hypochloraemia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hypokalaemia | 2/92 (2.2%) | 2 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Hyponatraemia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Hypoproteinaemia | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Obesity | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Type 2 diabetes mellitus | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 2/92 (2.2%) | 2 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Bone swelling | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Muscle spasms | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Pain in extremity | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Spinal osteoarthritis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adrenal adenoma | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Basal cell carcinoma | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Laryngeal cancer | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Lung neoplasm malignant | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Phaeochromocytoma | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Prostate cancer | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Nervous system disorders | ||||||
| Apallic syndrome | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Arachnoid cyst | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Brain oedema | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Coma | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Dizziness | 1/92 (1.1%) | 2 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Epilepsy | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Headache | 3/92 (3.3%) | 3 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Hypotonia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hypoxic-ischaemic encephalopathy | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Syncope | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Tremor | 3/92 (3.3%) | 4 | 2/96 (2.1%) | 2 | 0/91 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 0/92 (0%) | 0 | 2/96 (2.1%) | 2 | 0/91 (0%) | 0 |
| Depression | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Dysphoria | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Insomnia | 3/92 (3.3%) | 3 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Sleep disorder | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Diabetic nephropathy | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Dysuria | 0/92 (0%) | 0 | 1/96 (1%) | 2 | 0/91 (0%) | 0 |
| Haematuria | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Renal artery stenosis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Renal colic | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Renal cyst | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Urinary incontinence | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Vulvovaginal inflammation | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Bronchiectasis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Bronchospasm | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Chronic obstructive pulmonary disease | 24/92 (26.1%) | 33 | 32/96 (33.3%) | 42 | 28/91 (30.8%) | 41 |
| Chronic respiratory failure | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Cough | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Dyspnoea | 3/92 (3.3%) | 3 | 2/96 (2.1%) | 2 | 4/91 (4.4%) | 5 |
| Emphysema | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Epistaxis | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
| Haemoptysis | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hypoxia | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Oropharyngeal pain | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 1/91 (1.1%) | 1 |
| Paranasal cyst | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Pleural thickening | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Productive cough | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Pulmonary embolism | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Pulmonary fibrosis | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Pulmonary hypertension | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Rales | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Respiratory failure | 1/92 (1.1%) | 1 | 2/96 (2.1%) | 2 | 3/91 (3.3%) | 3 |
| Rhinorrhoea | 2/92 (2.2%) | 2 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Tonsillar erythema | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Upper respiratory tract congestion | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Wheezing | 2/92 (2.2%) | 2 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Decubitus ulcer | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Dermatitis | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Dermatitis acneiform | 1/92 (1.1%) | 1 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Dermatitis allergic | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Dry skin | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Hyperhidrosis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Pemphigoid | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Pruritus | 0/92 (0%) | 0 | 1/96 (1%) | 1 | 0/91 (0%) | 0 |
| Skin ulcer | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Surgical and medical procedures | ||||||
| Cataract operation | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Vascular disorders | ||||||
| Aortic aneurysm | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Aortic arteriosclerosis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Circulatory collapse | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 1/91 (1.1%) | 1 |
| Hypertension | 4/92 (4.3%) | 5 | 2/96 (2.1%) | 2 | 4/91 (4.4%) | 4 |
| Hypertensive crisis | 1/92 (1.1%) | 1 | 0/96 (0%) | 0 | 0/91 (0%) | 0 |
| Hypotension | 0/92 (0%) | 0 | 0/96 (0%) | 0 | 2/91 (2.2%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Ian Hodgson, Head of Clinical Operations |
|---|---|
| Organization | Mereo BioPharma Group |
| Phone | +44 3330237300 |
| enquiries@mereobiopharma.com |
Responsible Party:
Mereo BioPharma
ClinicalTrials.gov Identifier:
NCT02700919
Other Study ID Numbers:
- MBCT206
First Posted:
Mar 7, 2016
Last Update Posted:
Nov 30, 2020
Last Verified:
Nov 1, 2020