Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
Randomised, double-blind, parallel-group, multi-centre study evaluating three doses of losmapimod (2.5mg, 7.5 mg and 15 mg) twice daily (BID) versus placebo on exercise tolerance. Eligible subjects will be randomised to treatment after a one-week run-in period. The duration of the treatment period is 24 weeks. An estimated 1000 subjects will be screened to reach the target enrolment of approximately 600 randomised subjects.
Interventions
DRUGlosmapimod
comparison of different dosages of drug 2.5 mg, 7.5 mg or 15 mg
DRUGplacebo
placebo comparison with active
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society * FEV1/FVC ratio of ≤0.70 * FEV1 ≤ 80% of predicted normal * 6MWD \< 350m * male or female outpatients aged ≥40 years of age * current or prior history of ≥10 pack-years of cigarette smoking * aspartate transaminase (AST) or alanine transaminase (ALT) \<2x Upper Limit Normal (ULN) * alkaline phosphatase (alk phos), and bilirubin \<1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * QTc \<450 msec\* on baseline ECG. For subjects with baseline complete bundle branch block, the QTc must be \<480msec\* on baseline ECG.
Exclusion criteria
* current diagnosis of asthma * pregnant or lactating * α1-antitrypsin deficiency * lung resection * chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD * exacerbation of COPD within previous 12 weeks * treatment with roflumilast within previous 2 weeks and throughout the treatment period * lower respiratory tract infection that required the use of antibiotics within previous 12 weeks * long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day * participation in the acute phase of a Pulmonary Rehabilitation Program within 12 weeks or planned during the study * carcinoma that has not been in complete remission for at least 5 years * current or chronic history of liver disease * positive Hepatitis B surface antigen or positive Hepatitis C antibody * Body Mass Index (BMI) \> 35 * known or suspected history of alcohol or drug abuse within the last 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Baseline (Week 0) and Week 4, 12, 24 | Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = \[100 x (6MWD2 - 6MWD1)\]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24 | FVC is the total amount of air exhaled during the lung function test. and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.. Baseline visit was Visit 2 (Week 0). |
| Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Baseline (Week 0) and Week 12, 24 | The SGRQ-C questionnaire had 14 questions of COPD and participant had to rate each question. These 14 questions were separated to evaluate the three components of SGRQ-C. These three components were symptom component (question 1 to 7), activity component (question 9 and 12) and impact component (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Change from Baseline was calculated as the specified time point value minus the Baseline value. Baseline visit was Visit 2 (Week 0). |
| Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | Baseline(Week 0) and Week 12, 24 | A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood or air it contains). Plethysmography was used to assess IC, RV, TGV at FRC, SLV, and TLC. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0). |
| Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24 | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Pre and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.Baseline visit was Visit 2 (Week 0). |
| Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Baseline (Week 0) and Week 4, 8, 12, 24 | Least square mean ratio to Baseline of HsCRP was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits. |
| Total Number of Exacerbations Over 24 Weeks | Up to 24 weeks | An exacerbation of COPD is defined as a worsening of COPD symptoms requiring changes to normal treatment (other than increased use of relief salbutamol/albuterol) including antimicrobial therapy, short courses of oral steroids, other bronchodilator therapy and/or emergency treatment or hospitalization. |
| Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Baseline (Week 0) and Week 4, 8, 12, 24 | Least square mean ratio to Baseline of plasma fibrinogen was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits. |
Countries
Argentina, Czechia, Estonia, Germany, Norway, South Korea, Ukraine, United States
Participant flow
Recruitment details
This study was conducted from 04 November 2010 to 22 December 2011 across 65 centers worldwide. A total of 1000 participants with history of COPD exacerbations were planned to be screened and finally, 600 participants were planned to be randomized.
Pre-assignment details
A total of 886 participants were screened, 282 were screen failures, remaining 604 were randomized to receive the study drug. Out of the randomized 604, 2 participants did not receive the study drug due to error in randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo matching Losmapimod tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug. | 153 |
| Losmapimod 2.5 mg Participants received Losmapimod 2.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug. | 149 |
| Losmapimod 7.5 mg Participants received Losmapimod 7.5 mg tablet twice daily orally for a period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug. | 151 |
| Losmapimod 15 mg Participants received Losmapimod 7.5 mg tablet twice daily orally for 4 weeks followed by Losmapimod 15 mg for a total period of 24 weeks. During the run-in and treatment periods all participants continued their existing COPD therapy at a constant dose, including long-acting β2-agonists (LABA); long-acting muscarinic antagonists (LAMA); xanthines and/or inhaled corticosteroids (ICS). Participants were followed-up for 1 week after the last dose of the study drug. | 149 |
| Total | 602 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 10 | 12 | 16 |
| Overall Study | Lack of Efficacy | 7 | 2 | 2 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 |
| Overall Study | Physician Decision | 1 | 2 | 4 | 2 |
| Overall Study | Protocol-defined stopping criteria | 1 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 5 | 2 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 5 | 4 | 6 |
Baseline characteristics
| Characteristic | Placebo | Total | Losmapimod 15 mg | Losmapimod 7.5 mg | Losmapimod 2.5 mg |
|---|---|---|---|---|---|
| Age, Continuous | 63.9 Years STANDARD_DEVIATION 8.64 | 65.2 Years STANDARD_DEVIATION 8.62 | 64.8 Years STANDARD_DEVIATION 9.26 | 66.1 Years STANDARD_DEVIATION 7.76 | 66.1 Years STANDARD_DEVIATION 8.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 76 Participants | 23 Participants | 18 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 14 Participants | 8 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 131 Participants | 512 Participants | 118 Participants | 132 Participants | 131 Participants |
| Sex: Female, Male Female | 49 Participants | 189 Participants | 44 Participants | 48 Participants | 48 Participants |
| Sex: Female, Male Male | 104 Participants | 413 Participants | 105 Participants | 103 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 153 | 0 / 149 | 1 / 151 | 2 / 149 |
| other Total, other adverse events | 51 / 153 | 49 / 149 | 51 / 151 | 48 / 149 |
| serious Total, serious adverse events | 17 / 153 | 12 / 149 | 14 / 151 | 15 / 149 |
Outcome results
Primary
Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24
Exercise tolerance was assessed using the 6MWD. If a participant was recorded as having used supplemental oxygen or a walking aid (including sitting down then continuing walking) or a technical problem during a 6MWD then that walk was considered as invalid; otherwise the 6MWD was considered as valid. The baseline 6MWD value was defined as the longest distance walked, for a valid walk, at Visit 2. Variability between the distances walked during the first six-minute walk test (6MWD1) and the second six-minute walk test (6MWD2) being compared was defined as: Variability = \[100 x (6MWD2 - 6MWD1)\]/6MWD1. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).
Time frame: Baseline (Week 0) and Week 4, 12, 24
Population: Intent-to-treat (ITT) population consisted of all participants randomized to treatment and who received at least one dose of study drug. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 4 | 314.4 Meter (m) | Standard Error 2.79 |
| Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 24 | 330.6 Meter (m) | Standard Error 4.13 |
| Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 12 | 321.6 Meter (m) | Standard Error 3.53 |
| Losmapimod 2.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 4 | 311.8 Meter (m) | Standard Error 2.84 |
| Losmapimod 2.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 24 | 324.0 Meter (m) | Standard Error 4.19 |
| Losmapimod 2.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 12 | 322.2 Meter (m) | Standard Error 3.58 |
| Losmapimod 7.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 12 | 320.2 Meter (m) | Standard Error 3.5 |
| Losmapimod 7.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 4 | 313.2 Meter (m) | Standard Error 2.78 |
| Losmapimod 7.5 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 24 | 325.9 Meter (m) | Standard Error 4.09 |
| Losmapimod 15 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 4 | 319.9 Meter (m) | Standard Error 2.83 |
| Losmapimod 15 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 24 | 327.2 Meter (m) | Standard Error 4.27 |
| Losmapimod 15 mg | Change From Baseline in Six Minute Walk Distance (6MWD) at Week 4, 12 and 24 | Week 12 | 323.4 Meter (m) | Standard Error 3.65 |
Comparison: Placebo versus Losmapimod 2.5 mg at Week 4.p-value: 0.51795% CI: [-10.4, 5.2]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.76395% CI: [-8.9, 6.5]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 4p-value: 0.16495% CI: [-2.3, 13.3]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.995% CI: [-9.2, 10.5]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.78895% CI: [-11.1, 8.4]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 12p-value: 0.72295% CI: [-8.2, 11.8]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.2695% CI: [-18.2, 4.9]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.42295% CI: [-16.1, 6.8]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 24p-value: 0.56495% CI: [-15.1, 8.2]mixed model repeated measures
Secondary
Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24
Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Pre and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.Baseline visit was Visit 2 (Week 0).
Time frame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | 1 Millilitre(mL) | Standard Error 15.4 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | 3 Millilitre(mL) | Standard Error 15.6 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 8 Millilitre(mL) | Standard Error 15.7 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | 2 Millilitre(mL) | Standard Error 13.6 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | -1 Millilitre(mL) | Standard Error 15.8 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | -15 Millilitre(mL) | Standard Error 15 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | -7 Millilitre(mL) | Standard Error 15.4 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 9 Millilitre(mL) | Standard Error 15.2 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | -4 Millilitre(mL) | Standard Error 15.4 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | -13 Millilitre(mL) | Standard Error 15.5 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | -1 Millilitre(mL) | Standard Error 15.2 |
| Placebo | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | -2 Millilitre(mL) | Standard Error 12.8 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 7 Millilitre(mL) | Standard Error 15.4 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | 3 Millilitre(mL) | Standard Error 13.1 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | 15 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | -11 Millilitre(mL) | Standard Error 16 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | -6 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 7 Millilitre(mL) | Standard Error 16 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | 1 Millilitre(mL) | Standard Error 13.9 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | 3 Millilitre(mL) | Standard Error 15.3 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | -7 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | 1 Millilitre(mL) | Standard Error 15.2 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | -6 Millilitre(mL) | Standard Error 15.7 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | -22 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 14 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | -5 Millilitre(mL) | Standard Error 13.7 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 17 Millilitre(mL) | Standard Error 15.1 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | 4 Millilitre(mL) | Standard Error 15 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | 18 Millilitre(mL) | Standard Error 15.3 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | 20 Millilitre(mL) | Standard Error 15.5 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | 17 Millilitre(mL) | Standard Error 15.2 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | 14 Millilitre(mL) | Standard Error 12.8 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | 9 Millilitre(mL) | Standard Error 15.8 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | 20 Millilitre(mL) | Standard Error 15.3 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | 23 Millilitre(mL) | Standard Error 15.4 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | 24 Millilitre(mL) | Standard Error 15.6 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | 14 Millilitre(mL) | Standard Error 15.8 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | 16 Millilitre(mL) | Standard Error 16.2 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | 30 Millilitre(mL) | Standard Error 13.9 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | 27 Millilitre(mL) | Standard Error 15.9 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | 17 Millilitre(mL) | Standard Error 15.9 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | 34 Millilitre(mL) | Standard Error 15.5 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | 10 Millilitre(mL) | Standard Error 16.1 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | 10 Millilitre(mL) | Standard Error 16.1 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 51 Millilitre(mL) | Standard Error 16.3 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | 30 Millilitre(mL) | Standard Error 13.1 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 45 Millilitre(mL) | Standard Error 15.7 |
| Losmapimod 15 mg | Change From Baseline in Forced Expiratory Volume in 1 Sec (FEV1) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | 37 Millilitre(mL) | Standard Error 6.3 |
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.35595% CI: [-22, 61]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 4p-value: 0.96895% CI: [-39, 38]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.71595% CI: [-45, 31]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 4p-value: 0.15295% CI: [-10, 66]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.92295% CI: [-45, 40]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.69495% CI: [-34, 50]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 8p-value: 0.09495% CI: [-6.3, 79]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.45695% CI: [-26, 58]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 12p-value: 0.02395% CI: [6.7, 91]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 16p-value: 0.3295% CI: [-21, 65]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 16p-value: 0.26795% CI: [-19, 67]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 16p-value: 0.28995% CI: [-20, 67]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 20p-value: 0.78695% CI: [-37, 49]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 20p-value: 0.13495% CI: [-10, 76]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 20p-value: 0.19195% CI: [-15, 74]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.85295% CI: [-38, 46]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.39795% CI: [-24, 60]mixed model repeated measures
Comparison: Pre-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 24p-value: 0.49495% CI: [-28, 58]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.80795% CI: [-31, 40]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.38695% CI: [-20, 51]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 4p-value: 0.08995% CI: [-4.8, 67]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.95895% CI: [-45, 43]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.76695% CI: [-37, 50]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 8p-value: 0.0695% CI: [-1.7, 87]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.67895% CI: [-53, 35]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.63695% CI: [-33, 54]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 12p-value: 0.09495% CI: [-6.5, 83]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 16p-value: 0.77295% CI: [-49, 37]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 16p-value: 0.38795% CI: [-24, 61]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 16p-value: 0.24395% CI: [-18, 69]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 20p-value: 0.39895% CI: [-62, 25]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 20p-value: 0.21495% CI: [-16, 70]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 20p-value: 0.52695% CI: [-30, 58]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.67195% CI: [-53, 34]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.35595% CI: [-23, 64]mixed model repeated measures
Comparison: Post-Bronchodilator FEV1 for Placebo versus Losmapimod 15 mg at Week 24p-value: 0.78195% CI: [-38, 50]mixed model repeated measures
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24
FVC is the total amount of air exhaled during the lung function test. and post-bronchodilator spirometry was performed by the investigator. For post-bronchodilator measurements, spirometry was performed 10-15 minutes after inhalation of 400/360 microgram (mcg) of salbutamol/albuterol. Participants were asked to withhold all bronchodilator therapy (regularly used ipratropium bromide and salbutamol/albuterol used as required) for at least 4 hours prior to spirometric testing. The change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization values.. Baseline visit was Visit 2 (Week 0).
Time frame: Baseline(Week 0) and Week 4, 8, 12, 16, 20 and 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | -17 mL | Standard Error 31 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | -15 mL | Standard Error 31.2 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 3 mL | Standard Error 29.2 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | -24 mL | Standard Error 28.3 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | -23 mL | Standard Error 31.2 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | -50 mL | Standard Error 31.4 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | -34 mL | Standard Error 32.3 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 8 mL | Standard Error 29.8 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | -14 mL | Standard Error 31.2 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | -20 mL | Standard Error 31.9 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | -18 mL | Standard Error 32.1 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | -36 mL | Standard Error 25.8 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | -2 mL | Standard Error 30.4 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | -29 mL | Standard Error 26.3 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | -24 mL | Standard Error 32.6 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | -34 mL | Standard Error 31.6 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | -48 mL | Standard Error 31.4 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | -22 mL | Standard Error 29.7 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | -11 mL | Standard Error 28.9 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | -41 mL | Standard Error 32.4 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | -51 mL | Standard Error 32.2 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | -5 mL | Standard Error 31.8 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | -43 mL | Standard Error 31.5 |
| Losmapimod 2.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | -78 mL | Standard Error 31.5 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | -27 mL | Standard Error 29 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | -55 mL | Standard Error 28.3 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | -5 mL | Standard Error 29.6 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | -34 mL | Standard Error 31.3 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | -9 mL | Standard Error 32 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | -13 mL | Standard Error 31.9 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | -25 mL | Standard Error 32.1 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | -24 mL | Standard Error 25.8 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | -10 mL | Standard Error 31.2 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | -1 mL | Standard Error 30.8 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | -26 mL | Standard Error 31.1 |
| Losmapimod 7.5 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | -5 mL | Standard Error 31.2 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 24 | 25 mL | Standard Error 33.4 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 20 | 13 mL | Standard Error 33.4 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 4 | 33 mL | Standard Error 28.9 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 16 | 55 mL | Standard Error 32 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 16 | 8 mL | Standard Error 33.3 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 12 | 25 mL | Standard Error 32.4 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 24 | 20 mL | Standard Error 32.4 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 20 | 35 mL | Standard Error 32.6 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 8 | 69 mL | Standard Error 30.3 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 4 | 35 mL | Standard Error 26.4 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Pre-Bronchodilator Week 8 | 54 mL | Standard Error 30.9 |
| Losmapimod 15 mg | Change From Baseline in Forced Vital Capacity (FVC) at Week 4, 8, 12, 16, 20 and 24 | Post-Bronchodilator Week 12 | 52 mL | Standard Error 32.2 |
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 4p-value: 0.74295% CI: [-66, 93]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.44695% CI: [-109, 48]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 4p-value: 0.15795% CI: [-22, 137]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.82695% CI: [-93, 74]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.77395% CI: [-95, 70]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 8p-value: 0.27795% CI: [-38, 131]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.31995% CI: [-43, 132]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.71695% CI: [-71, 103]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 12p-value: 0.09895% CI: [-14, 163]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 16p-value: 0.83295% CI: [-80, 100]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 16p-value: 0.57995% CI: [-64, 114]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 16p-value: 0.36995% CI: [-49, 133]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 20p-value: 0.48795% CI: [-121, 58]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 20p-value: 0.88795% CI: [-82, 95]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 20p-value: 0.48695% CI: [-59, 123]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.60495% CI: [-113, 66]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.87295% CI: [-97, 82]mixed model repeated measures
Comparison: Pre-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 24p-value: 0.35595% CI: [-48, 134]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 4p-value: 0.83995% CI: [-65, 80]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.74195% CI: [-60, 84]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 4p-value: 0.05695% CI: [-1.8, 143]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.55495% CI: [-107, 57]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.47295% CI: [-110, 51]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 8p-value: 0.11695% CI: [-16, 149]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.80595% CI: [-98, 76]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.76395% CI: [-73, 100]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 12p-value: 0.09695% CI: [-13, 163]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 16p-value: 0.48595% CI: [-118, 56]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 16p-value: 0.70495% CI: [-69, 103]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 16p-value: 0.10895% CI: [-16, 159]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 20p-value: 0.79295% CI: [-98, 75]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 20p-value: 0.14795% CI: [-151, 23]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 20p-value: 0.27595% CI: [-39, 138]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.5395% CI: [-115, 59]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.82795% CI: [-77, 96]mixed model repeated measures
Comparison: Post-Bronchodilator FVC for Placebo versus Losmapimod 15 mg at Week 24p-value: 0.43495% CI: [-53, 124]mixed model repeated measures
Secondary
Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24
A plethysmograph is an instrument for measuring changes in volume within an organ or whole body (usually resulting from fluctuations in the amount of blood or air it contains). Plethysmography was used to assess IC, RV, TGV at FRC, SLV, and TLC. Change from Baseline was calculated as the endpoint value minus the Baseline value. Baseline visit was Visit 2 (Week 0).
Time frame: Baseline(Week 0) and Week 12, 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 12 | -26 mL | Standard Error 34.7 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 24 | -9 mL | Standard Error 39.2 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV, Week 12 | -14 mL | Standard Error 69.6 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV,Week 24 | -127 mL | Standard Error 74 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC, Week 12 | 8 mL | Standard Error 69.9 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC,Week 24 | -112 mL | Standard Error 70.2 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 12 | 24 mL | Standard Error 68.5 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 24 | -109 mL | Standard Error 67.1 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC, Week 12 | 50 mL | Standard Error 45.8 |
| Placebo | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC,Week 24 | 27 mL | Standard Error 52.3 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV, Week 12 | 21 mL | Standard Error 68.4 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC, Week 12 | 8 mL | Standard Error 45 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV,Week 24 | 11 mL | Standard Error 72.6 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC, Week 12 | 61 mL | Standard Error 68.8 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC,Week 24 | -37 mL | Standard Error 69 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 12 | 61 mL | Standard Error 67.5 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC,Week 24 | -93 mL | Standard Error 51.1 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 24 | 64 mL | Standard Error 65.8 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 12 | -4 mL | Standard Error 34.2 |
| Losmapimod 2.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 24 | -53 mL | Standard Error 38.4 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 24 | 86 mL | Standard Error 66 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 12 | 92 mL | Standard Error 67.1 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC,Week 24 | -10 mL | Standard Error 51.7 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 12 | -80 mL | Standard Error 34 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV,Week 24 | 72 mL | Standard Error 73 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC,Week 24 | 38 mL | Standard Error 69.3 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC, Week 12 | -18 mL | Standard Error 44.8 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 24 | -62 mL | Standard Error 38.7 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC, Week 12 | 25 mL | Standard Error 68.5 |
| Losmapimod 7.5 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV, Week 12 | 13 mL | Standard Error 68.1 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC, Week 12 | -38 mL | Standard Error 71.2 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 24 | 30 mL | Standard Error 68.9 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | TLC,Week 24 | -18 mL | Standard Error 72.3 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC,Week 24 | -7 mL | Standard Error 53.8 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | FRC, Week 12 | -43 mL | Standard Error 69.8 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 24 | -50 mL | Standard Error 40.4 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV, Week 12 | -43 mL | Standard Error 70.8 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | RV,Week 24 | 5 mL | Standard Error 76.1 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | IC,Week 12 | 13 mL | Standard Error 35.4 |
| Losmapimod 15 mg | Change From Baseline in Inspiratory Capacity (IC), Residual Volume(RV), Total Lung Capacity(TLC) , Thoracic Gas Volume (TGV) at Functional Residual Capacity ( FRC), Slow Vital Capacity (SVC) at Week 12 and 24 | SVC, Week 12 | 25 mL | Standard Error 46.5 |
Secondary
Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24
The SGRQ-C questionnaire had 14 questions of COPD and participant had to rate each question. These 14 questions were separated to evaluate the three components of SGRQ-C. These three components were symptom component (question 1 to 7), activity component (question 9 and 12) and impact component (question 8, 10, 11, 13 and 14). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Change from Baseline was calculated as the specified time point value minus the Baseline value. Baseline visit was Visit 2 (Week 0).
Time frame: Baseline (Week 0) and Week 12, 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 12 | 51.1 Score on scale | Standard Error 0.98 |
| Placebo | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 24 | 50.6 Score on scale | Standard Error 1.11 |
| Losmapimod 2.5 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 24 | 51.0 Score on scale | Standard Error 1.12 |
| Losmapimod 2.5 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 12 | 50.6 Score on scale | Standard Error 0.99 |
| Losmapimod 7.5 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 12 | 52.6 Score on scale | Standard Error 0.98 |
| Losmapimod 7.5 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 24 | 52.5 Score on scale | Standard Error 1.1 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 12 | 49.3 Score on scale | Standard Error 1.01 |
| Losmapimod 15 mg | Change From Baseline in St Georges Respiratory Questionnaire for COPD (SGRQ-C) at Week 12 and 24 | Week 24 | 49.2 Score on scale | Standard Error 1.15 |
Comparison: Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.68695% CI: [-3.3, 2.2]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.27995% CI: [-1.2, 4.2]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 12p-value: 0.19395% CI: [-4.6, 0.9]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.80395% CI: [-2.7, 3.5]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.22995% CI: [-1.2, 5]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 24p-value: 0.3995% CI: [-4.5, 1.8]mixed model repeated measures
Secondary
Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks
Least square mean ratio to Baseline of HsCRP was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.
Time frame: Baseline (Week 0) and Week 4, 8, 12, 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 4 | 1.06 Ratio | Standard Error 0.089 |
| Placebo | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 8 | 1.02 Ratio | Standard Error 0.086 |
| Placebo | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 12 | 1.09 Ratio | Standard Error 0.088 |
| Placebo | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 24 | 1.00 Ratio | Standard Error 0.088 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 8 | 1.06 Ratio | Standard Error 0.088 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 12 | 0.99 Ratio | Standard Error 0.09 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 24 | 0.95 Ratio | Standard Error 0.09 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 4 | 0.93 Ratio | Standard Error 0.091 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 12 | 0.79 Ratio | Standard Error 0.088 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 8 | 0.78 Ratio | Standard Error 0.085 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 24 | 0.81 Ratio | Standard Error 0.089 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 4 | 0.82 Ratio | Standard Error 0.089 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 24 | 0.86 Ratio | Standard Error 0.093 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 8 | 0.75 Ratio | Standard Error 0.089 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 4 | 0.77 Ratio | Standard Error 0.091 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of High Sensitivity C-reactive Protein (HsCRP) Over 24 Weeks | Week 12 | 0.69 Ratio | Standard Error 0.091 |
Comparison: Placebo versus Losmapimod 2.5 mg at Week 4p-value: 0.29195% CI: [0.68, 1.12]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 4p-value: 0.04695% CI: [0.61, 1]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 4p-value: 0.01495% CI: [0.57, 0.94]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.75595% CI: [0.82, 1.32]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.02995% CI: [0.6, 0.97]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 8p-value: 0.01595% CI: [0.58, 0.94]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.46895% CI: [0.71, 1.17]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.01195% CI: [0.57, 0.93]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 12p-value: 095% CI: [0.5, 0.82]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.69695% CI: [0.74, 1.22]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.09995% CI: [0.64, 1.04]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 24p-value: 0.25695% CI: [0.67, 1.11]mixed model repeated measures
Secondary
Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks
Least square mean ratio to Baseline of plasma fibrinogen was assessed at Week 4, 8, 12, 24. Blood samples for biomarker analysis were taken at selected visits.
Time frame: Baseline (Week 0) and Week 4, 8, 12, 24
Population: ITT population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 4 | 0.97 Ratio | Standard Error 0.022 |
| Placebo | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 8 | 1.01 Ratio | Standard Error 0.021 |
| Placebo | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 12 | 0.97 Ratio | Standard Error 0.022 |
| Placebo | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 24 | 0.94 Ratio | Standard Error 0.021 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 8 | 0.95 Ratio | Standard Error 0.021 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 12 | 0.96 Ratio | Standard Error 0.022 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 24 | 0.94 Ratio | Standard Error 0.022 |
| Losmapimod 2.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 4 | 0.96 Ratio | Standard Error 0.022 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 12 | 0.89 Ratio | Standard Error 0.021 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 8 | 0.91 Ratio | Standard Error 0.02 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 24 | 0.90 Ratio | Standard Error 0.021 |
| Losmapimod 7.5 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 4 | 0.89 Ratio | Standard Error 0.021 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 24 | 0.89 Ratio | Standard Error 0.022 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 8 | 0.89 Ratio | Standard Error 0.021 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 4 | 0.87 Ratio | Standard Error 0.022 |
| Losmapimod 15 mg | Least Square Mean Ratio to Baseline of Plasma Fibrinogen Over 24 Weeks | Week 12 | 0.87 Ratio | Standard Error 0.022 |
Comparison: Placebo versus Losmapimod 2.5 mg at Week 4p-value: 0.15795% CI: [0.91, 1.01]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 4p-value: 095% CI: [0.86, 0.95]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 4p-value: 095% CI: [0.86, 0.96]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 8p-value: 0.07295% CI: [0.9, 1]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 8p-value: 095% CI: [0.85, 0.95]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 8p-value: 095% CI: [0.83, 0.94]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 12p-value: 0.72895% CI: [0.93, 1.05]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 12p-value: 0.00295% CI: [0.86, 0.97]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 12p-value: 0.00195% CI: [0.84, 0.95]mixed model repeated measures
Comparison: Placebo versus Losmapimod 2.5 mg at Week 24p-value: 0.82395% CI: [0.95, 1.07]mixed model repeated measures
Comparison: Placebo versus Losmapimod 7.5 mg at Week 24p-value: 0.15395% CI: [0.9, 1.02]mixed model repeated measures
Comparison: Placebo versus Losmapimod 15 mg at Week 24p-value: 0.12695% CI: [0.9, 1.01]mixed model repeated measures
Secondary
Total Number of Exacerbations Over 24 Weeks
An exacerbation of COPD is defined as a worsening of COPD symptoms requiring changes to normal treatment (other than increased use of relief salbutamol/albuterol) including antimicrobial therapy, short courses of oral steroids, other bronchodilator therapy and/or emergency treatment or hospitalization.
Time frame: Up to 24 weeks
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Total Number of Exacerbations Over 24 Weeks | 48 Number of exacerbations |
| Losmapimod 2.5 mg | Total Number of Exacerbations Over 24 Weeks | 46 Number of exacerbations |
| Losmapimod 7.5 mg | Total Number of Exacerbations Over 24 Weeks | 47 Number of exacerbations |
| Losmapimod 15 mg | Total Number of Exacerbations Over 24 Weeks | 34 Number of exacerbations |
Comparison: Losmapimod 2.5 mg versus Placebop-value: 0.98995% CI: [0.64, 1.54]Negative Binomial regression model
Comparison: Placebo versus Losmapimod 7.5 mgp-value: 0.91595% CI: [0.64, 1.5]Negative Binomial regression model
Comparison: Placebo versus Losmapimod 15 mgp-value: 0.2195% CI: [0.47, 1.18]Negative Binomial regression model