Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, Exacerbation, Pulmonary Inflammation
Brief summary
This study will assess preliminary parameters of safety and efficacy of a single dose of BCT197 in patients with a Chronic Obstructive Pulmonary Disease (COPD) exacerbation.
Detailed description
This was an exploratory, double-blind, randomized, placebo-controlled, multicenter, adaptive parallel-group design study in four parts in patients with acute COPD exacerbation. In Part I, patients were randomized to receive either a single dose of 75mg BCT197, placebo or 40 mg oral prednisone in the ratio of 1:1:1. In Part II patients were randomized to receive either a single dose of 20 mg BCT197 or placebo in the ratio of 5:1. Patients in Parts I and II received their single dose on Day 1 of the study. In Parts III and IV patients were randomized to receive either BCT197 or placebo in a ratio of 5:1 at a dose of 20mg (Part III) or 75 mg (Part IV) with patients receiving a single dose on both Day 1 and Day 6 of the study.
Interventions
Sponsors
Novartis
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with COPD (Stage II to IV) with a COPD exacerbation. * Smoking history of 10 pack years. * Females must not be of child-bearing potential.
Exclusion criteria
* Use of steroids in the last 30 days or calcium channel blockers in the last 48 hours. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5, Day 10 | Change in FEV1 from baseline to Day 5 or baseline to Day 10 measured in mL Measure: FEV1 Change in Forced Expiry Volume in 1 second |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | Up to Day 29 | EXAcerbations of Chronic pulmonary disease tool patient reported outcome (EXACT-PRO) Rolling Average Improvement from Day 1 to Day 29. EXACT-PRO is a 14 point patient reported daily diary used to quantify and measure exacerbations of chronic obstructive pulmonary disease (COPD). Minimum score is 0 and Maximum score is 14 (higher scores indicate worsening indicative of an exacerbation). Reported value is LS mean improvement from at Day 29 compared to D1 of the study. |
Countries
Bulgaria, Romania, Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment A Single 75mg oral dose of BCT197 capsules + single oral dose of prednisone placebo capsules
BCT197
Prednisone placebo: capsules | 31 |
| Treatment B, E,G & I Matched placebo arms
BCT197 placebo: capsules
Prednisone placebo: capsules | 45 |
| Treatment C Single oral dose of BCT197 placebo capsules + single oral dose of 40mg prednisone capsules
Prednisone: capsules
BCT197 placebo: capsules | 30 |
| Treatment D Single oral dose of 20mg dose of BCT197 capsules
BCT197 | 25 |
| Treatment F Single oral dose of 20 mg dose of BCT197 capsules on Day 1 and Day 6
BCT197 | 27 |
| Treatment H Single oral dose of 75mg dose of BCT197 capsules on Day 1 and Day 6
BCT197 | 25 |
| Total | 183 |
Baseline characteristics
| Characteristic | Treatment A | Total | Treatment H | Treatment F | Treatment D | Treatment C | Treatment B, E,G & I |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 60 Years STANDARD_DEVIATION 8.6 | 62 Years STANDARD_DEVIATION 7.9 | 64 Years STANDARD_DEVIATION 6.7 | 61 Years STANDARD_DEVIATION 9.1 | 62 Years STANDARD_DEVIATION 8.7 | 63 Years STANDARD_DEVIATION 8 | 61 Years STANDARD_DEVIATION 6.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 183 Participants | 25 Participants | 27 Participants | 25 Participants | 30 Participants | 45 Participants |
| Sex: Female, Male Female | 8 Participants | 37 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 23 Participants | 146 Participants | 21 Participants | 23 Participants | 21 Participants | 26 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 31 | 0 / 45 | 2 / 30 | 1 / 25 | 1 / 27 | 1 / 25 |
| other Total, other adverse events | 5 / 31 | 20 / 45 | 16 / 30 | 13 / 25 | 14 / 27 | 16 / 25 |
| serious Total, serious adverse events | 2 / 31 | 4 / 45 | 5 / 30 | 2 / 25 | 3 / 27 | 3 / 25 |
Outcome results
Primary
Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second
Change in FEV1 from baseline to Day 5 or baseline to Day 10 measured in mL Measure: FEV1 Change in Forced Expiry Volume in 1 second
Time frame: Day 5, Day 10
Population: The PD analysis set included all participants without major protocol deviations that impacted efficacy/pharmacodynamic data. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Treatment A | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 155.1 mL |
| Treatment A | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 164.6 mL |
| Treatment B, E, G & I | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 100.8 mL |
| Treatment B, E, G & I | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 126.9 mL |
| Treatment C | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 48.9 mL |
| Treatment C | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 54.9 mL |
| Treatment D | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 106.3 mL |
| Treatment D | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 54.6 mL |
| Treatment F | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 134.4 mL |
| Treatment F | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 109.0 mL |
| Treatment H | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 5 | 200.6 mL |
| Treatment H | Change in FEV1 From Baseline to Day 5 or Baseline to Day 10 Measure: FEV1 Change in Forced Expiry Volume in 1 Second | Day 10 | 250.5 mL |
Comparison: LS Mean difference: Treatment A vs. Treatment B, E, G \& I (placebo) Day 595% CI: [-41.7, 150.1]
Comparison: LS Mean difference: Treatment C vs. Treatment B, E, G \& I (placebo) Day 595% CI: [-148.5, 44.5]
Comparison: LS Mean difference: Treatment D vs. Treatment B, E, G \& I (placebo) Day 595% CI: [-96, 106.9]
Comparison: LS Mean difference: Treatment F vs. Treatment B, E, G \& I (placebo) Day 595% CI: [-66.8, 133.9]
Comparison: LS Mean difference: Treatment H vs. Treatment B, E, G \& I (placebo) Day 595% CI: [-2.4, 202]
Comparison: LS Mean difference: Treatment A vs. Treatment B, E, G \& I (placebo) Day 1095% CI: [-107.1, 182.6]
Comparison: LS Mean difference: Treatment C vs. Treatment B, E, G \& I (placebo) Day 1095% CI: [-215.7, 71.8]
Comparison: LS Mean difference: Treatment D vs. Treatment B, E, G \& I (placebo) Day 1095% CI: [-241.5, 96.9]
Comparison: LS Mean difference: Treatment F vs. Treatment B, E, G \& I (placebo) Day 1095% CI: [-154.9, 119.2]
Comparison: LS Mean difference: Treatment H vs. Treatment B, E, G \& I (placebo) Day 1095% CI: [-15.8, 263]
Secondary
Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO
EXAcerbations of Chronic pulmonary disease tool patient reported outcome (EXACT-PRO) Rolling Average Improvement from Day 1 to Day 29. EXACT-PRO is a 14 point patient reported daily diary used to quantify and measure exacerbations of chronic obstructive pulmonary disease (COPD). Minimum score is 0 and Maximum score is 14 (higher scores indicate worsening indicative of an exacerbation). Reported value is LS mean improvement from at Day 29 compared to D1 of the study.
Time frame: Up to Day 29
Population: The PD analysis set included all participants without major protocol deviations that impacted efficacy/pharmacodynamic data. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment A | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 5.72 score on a scale |
| Treatment B, E, G & I | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 8.89 score on a scale |
| Treatment C | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 5.19 score on a scale |
| Treatment D | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 5.83 score on a scale |
| Treatment F | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 7.89 score on a scale |
| Treatment H | Rolling Average Improvement From Day 1 to Day 29 Using the EXACT-PRO 14 Point Patient Reported Outcome Measure: EXACT-PRO | 8.35 score on a scale |