Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.
Interventions
DRUGtetomilast
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
DRUGplacebo
Placebo for 104 weeks (2 years)
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, 40-75 yrs old,inclusive. * Rating of greater than or equal to 1 on the Goddard scale in assessment of emphysema severity by HRCT. * FEV1: FVC greater than 70% predicted. * At least 1 documented COPD exacerbation within the past year but not within 8 weeks of randomization. * Current or former smokers with a cigarette smoking history of at least 20 pack-years (or equivalent) and whose smoking status has not changed 60 days prior to screening.
Exclusion criteria
* Patients with asthma, active tuberculosis or bronchiectasis. * A respiratory tract infection within 30 days prior to the screening visit. * Any malignancy within the last 5 years with the exception of non-melanomatous skin cancer. * Uncontrolled cardiovascular, endocrine, blood, or nervous system disorders. * Uncontrolled condition with COPD exacerbation of level 2 or 3 in the 8-week period prior to randomization. * Systemic use of corticosteroids or other immunosuppressive agents within 30 days of the screening visit. * Subjects taking anticoagulants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) | Baseline to Week 104 | The analysis of the change from Baseline to Week 104 (last observation carried forward \[LOCF\]) in trough FEV1 is presented below. |
| Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Baseline to Week 104 | The analysis of the change from Baseline to Week 104 (LOCF) in the 20th percentile of lung density voxels (expressed in Hounsfield unit \[HU\] using quantitative HCRT) by visit and lung region is presented below. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in the 20th Percentile of Lung Density Voxels Expressed in HU Units for the Whole Lung (Whole Right + Whole Left) From Baseline to Week 104 | Baseline to Week 104 | The rate of change in lung density was calculated as the change in the 20th percentile of lung density voxels divided by the duration between the dates of measurement (month or year) where applicable. For example, if HRCT measurements are available over a span of 2 years, the annual rate of change was calculated as the difference over the 2 years divided by 2, where years between scans is given by years= floor(data of last scan - date of first scan + 1)/365.25. |
| Observed Rate of Change in Emphysema From Baseline to Week 104 | Baseline to Week 104 | The level of emphysema (g/L) within in a lung region is defined as the value of the selected percentile (10th, 15th, or 20th) in HU + 1000. The rate of change in the emphysema from baseline was calculated as the change in the level of emphysema from baseline to the specified visit divided by the time in years between the baseline and specified visit (i.e., \[date of visit - date of baseline visit + 1\]/365.25). |
| Change From Baseline to Week 104 in Cumulative Frequency of HU | Baseline and Week 104 | The area under the curve (AUC) is defined as the cumulative voxel frequency in HU (ie, the value of the density mask denominator). Blood samples (4 mL) for pharmacokinetic analysis were collected for the determination of plasma OPC-6535 concentrations at Predose on Day 1 and Weeks 26, 52, 78 and 104. |
| Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Baseline to Week 104 | Change from baseline in CT-derived lung volumes TLC and RV are presented in the below outcome data table. |
| Change From Baseline to Week 104 in Trough RV/TLC | Baseline to Week 104 | Change from Baseline in Trough RV/TLC is presented in the below outcome data table. |
| Change From Baseline to Week 104 in Trough Inspiratory Capacity | Baseline toWeek 104 | Change from Baseline in Trough Inspiratory Capacity is presented in the below outcome data table. |
| Percent Change From Baseline in Trough FEV1 From Baseline to Week 104 | Baseline to Week 104 | The percent change for the pulmonary function tests (PFT) from baseline was calculated for each study week as follows: % change from baseline = (\[value at Week X - value at baseline\] /value at baseline) x 100. |
| Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco) | Baseline to Week 104 | Change from Baseline in DLco is presented in the below outcome data table. |
| Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) | Baseline to Week 104 | Change from baseline in sRaw and sGaw is presented in the below outcome data table. |
| Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Baseline to Week 104 | Participants used the Breathlessness, Cough, and Sputum Scale (BCSS) as the diary to daily monitor and rate their symptoms of difficulty breathing, cough, and sputum. The scale allows patients to rate each symptom on a scale of 0 (no difficultly for breathing and sputum, or unaware of coughing) to 4 (an almost constant problem for breathing and sputum, or almost constant for cough). |
| Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications | Baseline to Week 104 | Participants recorded rescue medication use (albuterol and/or ipratropium bromide) in a rescue medication log. |
| Percentage of Participants With COPD Exacerbations by Group at Week 104 | Baseline and Week 104 | For the COPD exacerbations, baseline is defined as Randomization (Day 1). COPD exacerbations, defined as an acute worsening of COPD symptoms, were classified as being in one of 3 levels: Level I (can by self-managed by the participant); Level II (requires a physician visit), or Level III (requires a hospital visit). |
| Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Baseline and Week 104 | Percentage of participants experiencing a COPD exacerbation in a level 2 or higher are presented in the below outcome data table. |
| Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth) | Baseline to Week 104 | Change from baseline in trough FRCpleth is presented in the below outcome data table. |
| Density Mask Score Based on Specified Thresholds Including -950 HU | Baseline and Week 104 | The density mask score is defined as the percentage of lung density voxels that lie below a specified threshold in the lung region of interest. The higher the percentage of the participant's lung density voxels that lie below a specified threshold, the higher the level of the participant's emphysema in the lung region under consideration. Changes in the density mask score was assessed using only a single density mask threshold of -950 HU. |
Countries
United States
Participant flow
Recruitment details
Of the 84 participants treated in the trial, 38 completed the trial and 10 participants were ongoing at the time the sponsor discontinued the trial.
Pre-assignment details
Prior to randomization, each participant was in a 28- to 35-day screening period. Placebo was given for 14 days and a daily diary of symptom scores and actuations of albuterol/ipratropium bromide were collected.
Participants by arm
| Arm | Count |
|---|---|
| Tetomilast 50 mg Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | 51 |
| Placebo Participants were administered matching placebo for 104 weeks (2 years) | 33 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 4 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Met Withdrawal Criteria | 4 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Sponsor Discontinued Trial | 7 | 3 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Tetomilast 50 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 6.04 | 58.4 years STANDARD_DEVIATION 7.71 | 58.2 years STANDARD_DEVIATION 6.7 |
| Sex: Female, Male Female | 24 Participants | 17 Participants | 41 Participants |
| Sex: Female, Male Male | 27 Participants | 16 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 51 | 23 / 33 |
| serious Total, serious adverse events | 13 / 51 | 12 / 33 |
Outcome results
Primary
Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1)
The analysis of the change from Baseline to Week 104 (last observation carried forward \[LOCF\]) in trough FEV1 is presented below.
Time frame: Baseline to Week 104
Population: The Intent-to-Treat (ITT) population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable High-resolution computed tomography (HRCT) scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) | -0.001 L | Standard Deviation 0.2011 |
| Placebo | Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) | -0.083 L | Standard Deviation 0.3241 |
Comparison: Statistical analysis at Week 104.p-value: 0.176195% CI: [-0.0378, 0.2025]ANCOVA
Primary
Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels
The analysis of the change from Baseline to Week 104 (LOCF) in the 20th percentile of lung density voxels (expressed in Hounsfield unit \[HU\] using quantitative HCRT) by visit and lung region is presented below.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 43 and 25 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Lower (n= 43, 25) | -1.884 Hounsfield unit/year | Standard Deviation 11.5558 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Lower (n= 43, 25) | -0.713 Hounsfield unit/year | Standard Deviation 11.3439 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Middle (n= 43, 25) | -1.912 Hounsfield unit/year | Standard Deviation 6.0688 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Whole (n= 43, 25) | -2.409 Hounsfield unit/year | Standard Deviation 7.3861 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Upper (n= 43, 25) | -1.709 Hounsfield unit/year | Standard Deviation 9.8835 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Whole (n= 43, 25) | -0.882 Hounsfield unit/year | Standard Deviation 9.878 |
| Tetomilast 50 mg | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Upper (n= 43, 25) | -2.639 Hounsfield unit/year | Standard Deviation 7.9744 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Whole (n= 43, 25) | 0.587 Hounsfield unit/year | Standard Deviation 8.9852 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Upper (n= 43, 25) | 0.375 Hounsfield unit/year | Standard Deviation 7.1318 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Middle (n= 43, 25) | -0.831 Hounsfield unit/year | Standard Deviation 7.1709 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Lower (n= 43, 25) | 0.379 Hounsfield unit/year | Standard Deviation 11.0216 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Upper (n= 43, 25) | 0.686 Hounsfield unit/year | Standard Deviation 8.0797 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Left Lower (n= 43, 25) | 0.626 Hounsfield unit/year | Standard Deviation 11.4277 |
| Placebo | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels | Right Whole (n= 43, 25) | -0.225 Hounsfield unit/year | Standard Deviation 7.7509 |
Comparison: Statistical analysis of Right Upper region of the lung at Week 104.p-value: 0.13995% CI: [-6.77, 0.97]ANCOVA
Comparison: Statistical analysis of Right Middle region of the Lung at Week 104.p-value: 0.4695% CI: [-4.46, 2.04]ANCOVA
Comparison: Statistical analysis of Right Lower region of the Lung at Week 104.p-value: 0.45795% CI: [-7.98, 3.63]ANCOVA
Comparison: Statistical analysis of Left Upper region of the Lung at Week 104.p-value: 0.36295% CI: [-6.88, 2.54]ANCOVA
Comparison: Statistical analysis of Left Lower region of the Lung at Week 104.p-value: 0.6795% CI: [-6.94, 4.48]ANCOVA
Comparison: Statistical analysis of Right Whole region of the Lung at Week 104.p-value: 0.24495% CI: [-5.98, 1.55]ANCOVA
Comparison: Statistical analysis of Left Whole region of the Lung at Week 104.p-value: 0.57495% CI: [-6.23, 3.48]ANCOVA
Secondary
Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum
Participants used the Breathlessness, Cough, and Sputum Scale (BCSS) as the diary to daily monitor and rate their symptoms of difficulty breathing, cough, and sputum. The scale allows patients to rate each symptom on a scale of 0 (no difficultly for breathing and sputum, or unaware of coughing) to 4 (an almost constant problem for breathing and sputum, or almost constant for cough).
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 13 and 9 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily breath symptoms (n= 13, 9) | 0.13 units on a scale | Standard Deviation 0.6 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily cough symptoms (n= 13, 9) | 0.10 units on a scale | Standard Deviation 0.4 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily sputum symptoms (n= 13, 9) | 0.15 units on a scale | Standard Deviation 0.74 |
| Placebo | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily breath symptoms (n= 13, 9) | 0.20 units on a scale | Standard Deviation 0.95 |
| Placebo | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily cough symptoms (n= 13, 9) | -0.13 units on a scale | Standard Deviation 1.13 |
| Placebo | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum | Mean prior daily sputum symptoms (n= 13, 9) | 0.31 units on a scale | Standard Deviation 1.07 |
Comparison: Statistical analysis for mean prior daily breath symptomsp-value: 0.84595% CI: [-0.77, 0.64]ANCOVA
Comparison: Statistical analysis for mean prior daily cough symptomsp-value: 0.54995% CI: [-0.52, 0.94]ANCOVA
Comparison: Statistical analysis for mean prior daily sputum symptomsp-value: 0.71795% CI: [-0.93, 0.65]ANCOVA
Secondary
Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications
Participants recorded rescue medication use (albuterol and/or ipratropium bromide) in a rescue medication log.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 14 and 9 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications | -0.74 number of puffs | Standard Deviation 1.57 |
| Placebo | Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications | -2.52 number of puffs | Standard Deviation 3.82 |
Secondary
Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco)
Change from Baseline in DLco is presented in the below outcome data table.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 15 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco) | 0.021 mmoL/min/kPA | Standard Deviation 0.8485 |
| Placebo | Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco) | -0.625 mmoL/min/kPA | Standard Deviation 1.6288 |
p-value: 0.13495% CI: [-0.19, 1.4]ANCOVA
Secondary
Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV])
Change from baseline in CT-derived lung volumes TLC and RV are presented in the below outcome data table.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 22 and 16 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Upper (RV) (n= 22, 16) | 31.4 mL | Standard Deviation 145.3 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Upper (TLC) (n= 22, 16) | -0.7 mL | Standard Deviation 173.9 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Lower (RV) (n= 22, 16) | 13.0 mL | Standard Deviation 216.2 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Middle (TLC) (n= 22, 16) | 3.7 mL | Standard Deviation 71.2 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Lower (RV) (n= 22, 16) | 18.1 mL | Standard Deviation 186.2 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Lower (TLC) (n= 22, 16) | -12.5 mL | Standard Deviation 215.2 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Whole (RV) (n= 22, 16) | 35.3 mL | Standard Deviation 350.7 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Upper (TLC) (n= 22, 16) | 1.0 mL | Standard Deviation 141.8 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Middle (RV) (n= 22, 16) | -14.1 mL | Standard Deviation 65.7 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Lower (TLC) (n= 22, 16) | -6.9 mL | Standard Deviation 270.2 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Whole (RV) (n= 22, 16) | 23.8 mL | Standard Deviation 352 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Whole (TLC) (n= 22, 16) | -9.2 mL | Standard Deviation 341 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Whole (TLC) (n= 22, 16) | -6.1 mL | Standard Deviation 390.6 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Upper (RV) (n= 22, 16) | 11.0 mL | Standard Deviation 153.8 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Whole Lung (TLC) (n= 22, 16) | -15.2 mL | Standard Deviation 711.3 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Whole Lung (RV) (n= 22, 16) | 59.4 mL | Standard Deviation 693.3 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Whole Lung (TLC) (n= 22, 16) | -171.4 mL | Standard Deviation 584.4 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Upper (RV) (n= 22, 16) | -64.3 mL | Standard Deviation 216.5 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Middle (RV) (n= 22, 16) | -8.6 mL | Standard Deviation 63.6 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Lower (RV) (n= 22, 16) | -49.3 mL | Standard Deviation 254.8 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Upper (RV) (n= 22, 16) | -72.9 mL | Standard Deviation 212.9 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Lower (RV) (n= 22, 16) | -52.8 mL | Standard Deviation 220.7 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Whole (RV) (n= 22, 16) | -122.1 mL | Standard Deviation 504.5 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Whole (RV) (n= 22, 16) | -125.6 mL | Standard Deviation 401.8 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Whole Lung (RV) (n= 22, 16) | -247.8 mL | Standard Deviation 894.2 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Upper (TLC) (n= 22, 16) | -52.3 mL | Standard Deviation 144.5 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Middle (TLC) (n= 22, 16) | -6.1 mL | Standard Deviation 62.6 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Lower (TLC) (n= 22, 16) | -18.1 mL | Standard Deviation 159.2 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Upper (TLC) (n= 22, 16) | -59.1 mL | Standard Deviation 139.2 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Lower (TLC) (n= 22, 16) | -35.8 mL | Standard Deviation 195.6 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Left Whole (TLC) (n= 22, 16) | -95.1 mL | Standard Deviation 320.9 |
| Placebo | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) | Right Whole (TLC) (n= 22, 16) | -76.3 mL | Standard Deviation 291 |
Comparison: Statistical analysis of right upper lung region (RV) at Week 104.p-value: 0.18195% CI: [-38, 193.8]ANCOVA
Comparison: Statistical analysis of right middle lung region (RV) at Week 104.p-value: 0.78195% CI: [-48.8, 36.9]ANCOVA
Comparison: Statistical analysis of right lower lung region (RV) at Week 104.p-value: 0.44595% CI: [-77.8, 173.2]ANCOVA
Comparison: Statistical analysis of left upper lung region (RV) at Week 104.p-value: 0.25995% CI: [-48.1, 173.2]ANCOVA
Comparison: Statistical analysis of left lower lung region (RV) at Week 104.p-value: 0.63995% CI: [-105.6, 169.6]ANCOVA
Comparison: Statistical analysis of right whole lung region (RV) at Week 104.p-value: 0.40895% CI: [-145.9, 350.5]ANCOVA
Comparison: Statistical analysis of left whole lung region (RV) at Week 104.p-value: 0.44595% CI: [-138.8, 309.2]ANCOVA
Comparison: Statistical analysis of whole lung region (RV) at Week 104.p-value: 0.42195% CI: [-279.6, 654.8]ANCOVA
Comparison: Statistical analysis of right upper lung region (TLC) at Week 104.p-value: 0.35395% CI: [-58.5, 159.9]ANCOVA
Comparison: Statistical analysis of right middle lung region (TLC) at Week 104.p-value: 0.6695% CI: [-35.3, 55]ANCOVA
Comparison: Statistical analysis of right lower lung region (TLC) at Week 104.p-value: 0.85995% CI: [-110.7, 132.1]ANCOVA
Comparison: Statistical analysis of left upper lung region (TLC)at Week 104.p-value: 0.25395% CI: [-38.4, 141.4]ANCOVA
Comparison: Statistical analysis of left lower lung region (TLC) at Week 104.p-value: 0.75495% CI: [-126, 172.6]ANCOVA
Comparison: Statistical analysis of right whole lung region (TLC) at Week 104.p-value: 0.54695% CI: [-145.1, 269.5]ANCOVA
Comparison: Statistical analysis of left whole lung region (TLC) at Week 104.p-value: 0.55495% CI: [-155.5, 285.3]ANCOVA
Comparison: Statistical analysis of whole lung region (TLC) at Week 104.p-value: 0.52495% CI: [-284.9, 549.4]ANCOVA
Secondary
Change From Baseline to Week 104 in Cumulative Frequency of HU
The area under the curve (AUC) is defined as the cumulative voxel frequency in HU (ie, the value of the density mask denominator). Blood samples (4 mL) for pharmacokinetic analysis were collected for the determination of plasma OPC-6535 concentrations at Predose on Day 1 and Weeks 26, 52, 78 and 104.
Time frame: Baseline and Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 16 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Upper (n= 23, 16) | 4429363 Hounsfield unit*hour | Standard Deviation 1696731 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Middle (n= 23, 16) | 1474625 Hounsfield unit*hour | Standard Deviation 409858 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Lower (n= 23, 16) | 4507375 Hounsfield unit*hour | Standard Deviation 1302992 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Upper (n= 23, 16) | 4818524 Hounsfield unit*hour | Standard Deviation 1541192 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Lower (n= 23, 16) | 4351407 Hounsfield unit*hour | Standard Deviation 1677740 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Whole (n= 23, 16) | 10411363 Hounsfield unit*hour | Standard Deviation 2651975 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Whole (n= 23, 16) | 9169931 Hounsfield unit*hour | Standard Deviation 2630471 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Cumulative Frequency of HU | Whole Lung (n= 23, 16) | 19581293 Hounsfield unit*hour | Standard Deviation 5212292 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Whole Lung (n= 23, 16) | 20093377 Hounsfield unit*hour | Standard Deviation 5022730 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Upper (n= 23, 16) | 4596228 Hounsfield unit*hour | Standard Deviation 1012400 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Lower (n= 23, 16) | 4392819 Hounsfield unit*hour | Standard Deviation 1256283 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Middle (n= 23, 16) | 1500073 Hounsfield unit*hour | Standard Deviation 644286 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Whole (n= 23, 16) | 9498425 Hounsfield unit*hour | Standard Deviation 2471947 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Lower (n= 23, 16) | 4498652 Hounsfield unit*hour | Standard Deviation 1703957 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Right Whole (n= 23, 16) | 10594953 Hounsfield unit*hour | Standard Deviation 2678348 |
| Placebo | Change From Baseline to Week 104 in Cumulative Frequency of HU | Left Upper (n= 23, 16) | 5105606 Hounsfield unit*hour | Standard Deviation 1574676 |
Comparison: Statistical analysis of right upper region of the lung at Week 104.p-value: 0.2295% CI: [-219976, 922951]ANCOVA
Comparison: Statistical analysis of right middle region of the lung at Week 104p-value: 0.14695% CI: [-37651, 243723]ANCOVA
Comparison: Statistical analysis of right lower region of the lung at Week 104p-value: 0.32295% CI: [-252728, 747444]ANCOVA
Comparison: Statistical analysis of left upper region of the lung at Week 104.p-value: 0.14195% CI: [-126518, 851286]ANCOVA
Comparison: Statistical analysis of left lower region of the lung at Week 104.p-value: 0.32595% CI: [-303329, 891733]ANCOVA
Comparison: Statistical analysis of right whole region of the lung at Week 104.p-value: 0.25895% CI: [-439692, 1591457]ANCOVA
Comparison: Statistical analysis of left whole region of the lung at Week 104.p-value: 0.24795% CI: [-426928, 1605673]ANCOVA
Comparison: Statistical analysis of whole lung region of the lung at Week 104.p-value: 0.25195% CI: [-855009, 3167645]ANCOVA
Secondary
Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw)
Change from baseline in sRaw and sGaw is presented in the below outcome data table.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 15 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) | sRaw | -0.29 kPa.sec | Standard Deviation 1.11 |
| Tetomilast 50 mg | Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) | sGaw | 0.11 kPa.sec | Standard Deviation 0.584 |
| Placebo | Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) | sRaw | 0.47 kPa.sec | Standard Deviation 1.387 |
| Placebo | Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) | sGaw | -0.07 kPa.sec | Standard Deviation 0.293 |
Comparison: Statistical analysis for sRawp-value: 0.07495% CI: [-1.5, 0.07]ANCOVA
Comparison: Statistical analysis for sGawp-value: 0.15595% CI: [-0.09, 0.52]ANCOVA
Secondary
Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth)
Change from baseline in trough FRCpleth is presented in the below outcome data table.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 15 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth) | -0.010 mL | Standard Deviation 1.013 |
| Placebo | Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth) | 0.029 mL | Standard Deviation 0.529 |
p-value: 0.466195% CI: [-0.6892, 0.3221]ANCOVA
Secondary
Change From Baseline to Week 104 in Trough Inspiratory Capacity
Change from Baseline in Trough Inspiratory Capacity is presented in the below outcome data table.
Time frame: Baseline toWeek 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 25 and 14 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Trough Inspiratory Capacity | 0.074 mL | Standard Deviation 0.574 |
| Placebo | Change From Baseline to Week 104 in Trough Inspiratory Capacity | -0.225 mL | Standard Deviation 0.384 |
p-value: 0.125295% CI: [-0.073, 0.571]ANCOVA
Secondary
Change From Baseline to Week 104 in Trough RV/TLC
Change from Baseline in Trough RV/TLC is presented in the below outcome data table.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were n= 21 and 14 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Change From Baseline to Week 104 in Trough RV/TLC | 0.01 unitless | Standard Deviation 0.12 |
| Placebo | Change From Baseline to Week 104 in Trough RV/TLC | 0.01 unitless | Standard Deviation 0.07 |
p-value: 0.584395% CI: [-0.07, 0.04]ANCOVA
Secondary
Density Mask Score Based on Specified Thresholds Including -950 HU
The density mask score is defined as the percentage of lung density voxels that lie below a specified threshold in the lung region of interest. The higher the percentage of the participant's lung density voxels that lie below a specified threshold, the higher the level of the participant's emphysema in the lung region under consideration. Changes in the density mask score was assessed using only a single density mask threshold of -950 HU.
Time frame: Baseline and Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 16 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Upper (n= 23, 16) | 0.57 Hounsfield unit | Standard Deviation 3.217 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Middle (n= 23, 16) | 0.96 Hounsfield unit | Standard Deviation 2.992 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Lower (n= 23, 16) | 1.17 Hounsfield unit | Standard Deviation 4.141 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Upper (n= 23, 16) | 1.17 Hounsfield unit | Standard Deviation 3.713 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Lower (n= 23, 16) | 1.22 Hounsfield unit | Standard Deviation 4.306 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Whole (n= 23, 16) | 0.96 Hounsfield unit | Standard Deviation 3.483 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Whole (n= 23, 16) | 1.09 Hounsfield unit | Standard Deviation 3.667 |
| Tetomilast 50 mg | Density Mask Score Based on Specified Thresholds Including -950 HU | Whole Lung (n= 23, 16) | 1.04 Hounsfield unit | Standard Deviation 3.431 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Whole Lung (n= 23, 16) | -1.00 Hounsfield unit | Standard Deviation 4.336 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Upper (n= 23, 16) | -0.38 Hounsfield unit | Standard Deviation 4.425 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Lower (n= 23, 16) | -1.06 Hounsfield unit | Standard Deviation 5.221 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Middle (n= 23, 16) | -1.56 Hounsfield unit | Standard Deviation 4.98 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Whole (n= 23, 16) | -1.00 Hounsfield unit | Standard Deviation 4.719 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Lower (n= 23, 16) | -0.75 Hounsfield unit | Standard Deviation 4.494 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Right Whole (n= 23, 16) | -0.81 Hounsfield unit | Standard Deviation 4.151 |
| Placebo | Density Mask Score Based on Specified Thresholds Including -950 HU | Left Upper (n= 23, 16) | -1.06 Hounsfield unit | Standard Deviation 4.823 |
Comparison: Statistical analysis of Right Lower region of the Lung at Week 104.p-value: 0.16395% CI: [-0.83, 4.77]ANCOVA
Comparison: Statistical analysis of Right Upper region of the Lung at Week 104.p-value: 0.43695% CI: [-1.53, 3.47]ANCOVA
Comparison: Statistical analysis of Right Middle region of the Lung at Week 104.p-value: 0.06795% CI: [-0.17, 4.79]ANCOVA
Comparison: Statistical analysis of Left Upper region of the Lung at Week 104.p-value: 0.10295% CI: [-0.48, 5.02]ANCOVA
Comparison: Statistical analysis of Left Lower region of the Lung at Week 104.p-value: 0.16295% CI: [-0.89, 5.12]ANCOVA
Comparison: Statistical analysis of Right Whole region of the Lung at Week 104.p-value: 0.1695% CI: [-0.73, 4.29]ANCOVA
Comparison: Statistical analysis of Left Whole region of the Lung at Week 104.p-value: 0.12295% CI: [-0.58, 4.75]ANCOVA
Comparison: Statistical analysis of Whole Lung region of the Lung at Week 104.p-value: 0.10695% CI: [-0.46, 4.56]ANCOVA
Secondary
Observed Rate of Change in Emphysema From Baseline to Week 104
The level of emphysema (g/L) within in a lung region is defined as the value of the selected percentile (10th, 15th, or 20th) in HU + 1000. The rate of change in the emphysema from baseline was calculated as the change in the level of emphysema from baseline to the specified visit divided by the time in years between the baseline and specified visit (i.e., \[date of visit - date of baseline visit + 1\]/365.25).
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 23 and 16 respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Lower (n= 23, 16) | -0.62 g/L | Standard Deviation 7.88 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Upper (n= 23, 16) | -1.49 g/L | Standard Deviation 5.66 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Whole (n= 23, 16) | -0.79 g/L | Standard Deviation 5.23 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Middle (n= 23, 16) | -0.87 g/L | Standard Deviation 3.96 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Whole (n= 23, 16) | -0.95 g/L | Standard Deviation 5.73 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Upper (n= 23, 16) | -0.64 g/L | Standard Deviation 4.31 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Whole Lung (n= 23, 16) | -0.85 g/L | Standard Deviation 5.3 |
| Tetomilast 50 mg | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Lower (n= 23, 16) | -0.53 g/L | Standard Deviation 7.71 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Whole Lung (n= 23, 16) | 0.74 g/L | Standard Deviation 7.28 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Upper (n= 23, 16) | 1.83 g/L | Standard Deviation 7.04 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Upper (n= 23, 16) | 0.58 g/L | Standard Deviation 6.27 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Middle (n= 23, 16) | 0.28 g/L | Standard Deviation 5.77 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Lower (n= 23, 16) | 0.42 g/L | Standard Deviation 9.62 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Whole (n= 23, 16) | 0.50 g/L | Standard Deviation 6.78 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Left Whole (n= 23, 16) | 1.14 g/L | Standard Deviation 7.73 |
| Placebo | Observed Rate of Change in Emphysema From Baseline to Week 104 | Right Lower (n= 23, 16) | 0.39 g/L | Standard Deviation 9.16 |
Comparison: Statistical analysis of right upper region of the lung at Week 104.p-value: 0.51995% CI: [-4.42, 2.27]ANCOVA
Comparison: Statistical analysis of right middle region of the lung at Week 104.p-value: 0.46395% CI: [-3.92, 1.82]ANCOVA
Comparison: Statistical analysis of right lower region of the lung at Week 104.p-value: 0.59895% CI: [-6.74, 3.94]ANCOVA
Comparison: Statistical analysis of left upper region of the lung at Week 104.p-value: 0.14295% CI: [-6.92, 1.03]ANCOVA
Comparison: Statistical analysis of left lower region of the lung at Week 104.p-value: 0.75795% CI: [-6.26, 4.59]ANCOVA
Comparison: Statistical analysis of right whole region of the lung at Week 104.p-value: 0.595% CI: [-5.03, 2.5]ANCOVA
Comparison: Statistical analysis of left whole region of the lung at Week 104.p-value: 0.35395% CI: [-6.09, 2.23]ANCOVA
Comparison: Statistical analysis of whole region of the lung at Week 104.p-value: 0.43895% CI: [-5.43, 2.4]ANCOVA
Secondary
Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher)
Percentage of participants experiencing a COPD exacerbation in a level 2 or higher are presented in the below outcome data table.
Time frame: Baseline and Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tetomilast 50 mg | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 2 or Higher (Baseline) | 0.0 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 2 or Higher (Week 104) | 8.3 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 1 or No Exacerbation (Baseline) | 100.0 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 1 or No Exacerbation (Week 104) | 39.6 percentage of participants |
| Placebo | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 1 or No Exacerbation (Baseline) | 100.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 2 or Higher (Baseline) | 0.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 1 or No Exacerbation (Week 104) | 50.0 percentage of participants |
| Placebo | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) | Level 2 or Higher (Week 104) | 3.6 percentage of participants |
Comparison: Statistical analysis at Week 104p-value: 0.63Fisher Exact
Secondary
Percentage of Participants With COPD Exacerbations by Group at Week 104
For the COPD exacerbations, baseline is defined as Randomization (Day 1). COPD exacerbations, defined as an acute worsening of COPD symptoms, were classified as being in one of 3 levels: Level I (can by self-managed by the participant); Level II (requires a physician visit), or Level III (requires a hospital visit).
Time frame: Baseline and Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level I (Baseline) (n= 48, 28) | 0.0 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level I (Week 104) (n= 23, 15) | 4.3 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level II (Baseline) (n= 48, 28) | 0.0 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level II (Week 104) (n= 23, 15) | 8.7 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level III (Baseline) (n= 48, 28) | 0.0 percentage of participants |
| Tetomilast 50 mg | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level III (Week 104) (n= 23, 15) | 8.7 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level III (Baseline) (n= 48, 28) | 0.0 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level I (Baseline) (n= 48, 28) | 0.0 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level II (Week 104) (n= 23, 15) | 6.7 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level I (Week 104) (n= 23, 15) | 6.7 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level III (Week 104) (n= 23, 15) | 0.0 percentage of participants |
| Placebo | Percentage of Participants With COPD Exacerbations by Group at Week 104 | Level II (Baseline) (n= 48, 28) | 0.0 percentage of participants |
Comparison: Statistical analysis for level I (self management) at week 104.p-value: 1Fisher Exact
Comparison: Statistical analysis for level II (physician visit) at week 104.p-value: 1Fisher Exact
Comparison: Statistical analysis for level III (hospital visit) at week 104.p-value: 0.5092Fisher Exact
Secondary
Percent Change From Baseline in Trough FEV1 From Baseline to Week 104
The percent change for the pulmonary function tests (PFT) from baseline was calculated for each study week as follows: % change from baseline = (\[value at Week X - value at baseline\] /value at baseline) x 100.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 28 and 18 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Percent Change From Baseline in Trough FEV1 From Baseline to Week 104 | -0.771 percentage change | Standard Deviation 14.4521 |
| Placebo | Percent Change From Baseline in Trough FEV1 From Baseline to Week 104 | -7.071 percentage change | Standard Deviation 22.911 |
Secondary
Rate of Change in the 20th Percentile of Lung Density Voxels Expressed in HU Units for the Whole Lung (Whole Right + Whole Left) From Baseline to Week 104
The rate of change in lung density was calculated as the change in the 20th percentile of lung density voxels divided by the duration between the dates of measurement (month or year) where applicable. For example, if HRCT measurements are available over a span of 2 years, the annual rate of change was calculated as the difference over the 2 years divided by 2, where years between scans is given by years= floor(data of last scan - date of first scan + 1)/365.25.
Time frame: Baseline to Week 104
Population: The ITT population consisted of all randomized participants with non-missing baseline data and at least one post-baseline trough FEV1 measurement or evaluable HRCT scan. The number of participants analyzed at Week 104 were N = 46 and 26 respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tetomilast 50 mg | Rate of Change in the 20th Percentile of Lung Density Voxels Expressed in HU Units for the Whole Lung (Whole Right + Whole Left) From Baseline to Week 104 | -1.375 Hounsfield unit/year | Standard Deviation 7.909 |
| Placebo | Rate of Change in the 20th Percentile of Lung Density Voxels Expressed in HU Units for the Whole Lung (Whole Right + Whole Left) From Baseline to Week 104 | 0.115 Hounsfield unit/year | Standard Deviation 8.166 |
Comparison: LS Mean Difference between Tetomilast and Placebo at Week 104.p-value: 0.46995% CI: [-5.32, 2.48]ANCOVA