EMPHASIS: Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT00874497
Collaborator
(none)
84
15
2
77
5.6
0.1
Study Details
Study Description
Brief Summary
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
84 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multi-center, Randomized, Double-blind, Placebo-controlled Pilot Study to Assess the Pharmacodynamics, Efficacy and Safety of 50 mg Tetomilast Administered as Oral Tablets in Patients With Chronic Obstructive Pulmonary Disease Associated With Emphysema THIS STUDY IS CLOSED TO ENROLLMENT AND NEW SITES
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Jul 1, 2015
Actual Study Completion Date
:
Aug 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Tetomilast
|
Drug: tetomilast
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
|
| Placebo Comparator: 2 Placebo
|
Drug: placebo
Placebo for 104 weeks (2 years)
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UAB Lung Health Center | Birmingham | Alabama | United States | 35294 |
| 2 | Los Angeles Biomedical Institute | Torrance | California | United States | 90502 |
| 3 | Pulmonary Disease Specialist/PDS Research | Kissimmee | Florida | United States | 34741 |
| 4 | Well Pharma Medical Research | Miami | Florida | United States | 33143 |
| 5 | Florida Premier Research Institute | Winter Park | Florida | United States | 32789 |
| 6 | Georgia Clinical Research | Austell | Georgia | United States | 30106 |
| 7 | Illinios Lung Institute | Peoria | Illinois | United States | 61606 |
| 8 | University of Louisville, Pulmonary Division | Louisville | Kentucky | United States | 40202 |
| 9 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 10 | Temple University Hospital | Philadelphia | Pennsylvania | United States | 19140 |
| 11 | Spartanburg Medical Research | Spartanburg | South Carolina | United States | 29303 |
| 12 | Texas Institute of Chest and Sleep Disorders, PA | Houston | Texas | United States | 77034 |
| 13 | Diagnostics Research Group | San Antonio | Texas | United States | 78229 |
| 14 | Pulmonary Associates of Richmond | Richmond | Virginia | United States | 23225 |
| 15 | Multicare Pulmonary Specialist | Tacoma | Washington | United States | 98405 |
Sponsors and Collaborators
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00874497
Other Study ID Numbers:
- 197-08-250
First Posted:
Apr 2, 2009
Last Update Posted:
Apr 17, 2017
Last Verified:
Mar 1, 2017
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Period Title: Overall Study | ||
| STARTED | 51 | 33 |
| COMPLETED | 23 | 15 |
| NOT COMPLETED | 28 | 18 |
Baseline Characteristics
| Arm/Group Title | Tetomilast 50 mg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) | Total of all reporting groups |
| Overall Participants | 51 | 33 | 84 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58.0
(6.04)
|
58.4
(7.71)
|
58.2
(6.70)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
24
47.1%
|
17
51.5%
|
41
48.8%
|
| Male |
27
52.9%
|
16
48.5%
|
43
51.2%
|
Outcome Measures
| Title | Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 48 | 28 |
| Mean (Standard Deviation) [L] |
-0.001
(0.2011)
|
-0.083
(0.3241)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1761 |
| Comments | P-values are based on Analysis of Covariance (ANCOVA) model of the change FEV1 from baseline to the specified study week using treatment group and current smoking status as fixed effects and the baseline FEV1 value as a covariate. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.0824 | |
| Confidence Interval |
(2-Sided) 95% -0.0378 to 0.2025 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 43 | 25 |
| Right Upper (n= 43, 25) |
-2.639
(7.9744)
|
0.375
(7.1318)
|
| Right Middle (n= 43, 25) |
-1.912
(6.0688)
|
-0.831
(7.1709)
|
| Right Lower (n= 43, 25) |
-1.884
(11.5558)
|
0.379
(11.0216)
|
| Left Upper (n= 43, 25) |
-1.709
(9.8835)
|
0.686
(8.0797)
|
| Left Lower (n= 43, 25) |
-0.713
(11.3439)
|
0.626
(11.4277)
|
| Right Whole (n= 43, 25) |
-2.409
(7.3861)
|
-0.225
(7.7509)
|
| Left Whole (n= 43, 25) |
-0.882
(9.8780)
|
0.587
(8.9852)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Upper region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.139 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.904 | |
| Confidence Interval |
(2-Sided) 95% -6.77 to 0.97 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Middle region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.460 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.210 | |
| Confidence Interval |
(2-Sided) 95% -4.46 to 2.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Lower region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.176 | |
| Confidence Interval |
(2-Sided) 95% -7.98 to 3.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Upper region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.362 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.167 | |
| Confidence Interval |
(2-Sided) 95% -6.88 to 2.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Lower region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.670 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.225 | |
| Confidence Interval |
(2-Sided) 95% -6.94 to 4.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Whole region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.244 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.218 | |
| Confidence Interval |
(2-Sided) 95% -5.98 to 1.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Whole region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.574 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.374 | |
| Confidence Interval |
(2-Sided) 95% -6.23 to 3.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent Change From Baseline in Trough FEV1 From Baseline to Week 104 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 28 | 18 |
| Mean (Standard Deviation) [percentage change] |
-0.771
(14.4521)
|
-7.071
(22.9110)
|
| Title | Density Mask Score Based on Specified Thresholds Including -950 HU |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 16 |
| Right Upper (n= 23, 16) |
0.57
(3.217)
|
-0.38
(4.425)
|
| Right Middle (n= 23, 16) |
0.96
(2.992)
|
-1.56
(4.980)
|
| Right Lower (n= 23, 16) |
1.17
(4.141)
|
-0.75
(4.494)
|
| Left Upper (n= 23, 16) |
1.17
(3.713)
|
-1.06
(4.823)
|
| Left Lower (n= 23, 16) |
1.22
(4.306)
|
-1.06
(5.221)
|
| Right Whole (n= 23, 16) |
0.96
(3.483)
|
-0.81
(4.151)
|
| Left Whole (n= 23, 16) |
1.09
(3.667)
|
-1.00
(4.719)
|
| Whole Lung (n= 23, 16) |
1.04
(3.431)
|
-1.00
(4.336)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Upper region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.436 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% -1.53 to 3.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Middle region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.067 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.31 | |
| Confidence Interval |
(2-Sided) 95% -0.17 to 4.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Lower region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.163 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.97 | |
| Confidence Interval |
(2-Sided) 95% -0.83 to 4.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Upper region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.102 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.27 | |
| Confidence Interval |
(2-Sided) 95% -0.48 to 5.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Lower region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.162 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.11 | |
| Confidence Interval |
(2-Sided) 95% -0.89 to 5.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Right Whole region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.160 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1.78 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to 4.29 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Left Whole region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.122 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.08 | |
| Confidence Interval |
(2-Sided) 95% -0.58 to 4.75 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of Whole Lung region of the Lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.106 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to 4.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 46 | 26 |
| Mean (Standard Deviation) [Hounsfield unit/year] |
-1.375
(7.909)
|
0.115
(8.166)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | LS Mean Difference between Tetomilast and Placebo at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.469 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.423 | |
| Confidence Interval |
(2-Sided) 95% -5.32 to 2.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Observed Rate of Change in Emphysema From Baseline to Week 104 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 16 |
| Right Upper (n= 23, 16) |
-0.64
(4.31)
|
0.58
(6.27)
|
| Right Middle (n= 23, 16) |
-0.87
(3.96)
|
0.28
(5.77)
|
| Right Lower (n= 23, 16) |
-0.53
(7.71)
|
0.39
(9.16)
|
| Left Upper (n= 23, 16) |
-1.49
(5.66)
|
1.83
(7.04)
|
| Left Lower (n= 23, 16) |
-0.62
(7.88)
|
0.42
(9.62)
|
| Right Whole (n= 23, 16) |
-0.79
(5.23)
|
0.50
(6.78)
|
| Left Whole (n= 23, 16) |
-0.95
(5.73)
|
1.14
(7.73)
|
| Whole Lung (n= 23, 16) |
-0.85
(5.30)
|
0.74
(7.28)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right upper region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.519 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.07 | |
| Confidence Interval |
(2-Sided) 95% -4.42 to 2.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right middle region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.463 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.05 | |
| Confidence Interval |
(2-Sided) 95% -3.92 to 1.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right lower region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.598 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.40 | |
| Confidence Interval |
(2-Sided) 95% -6.74 to 3.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left upper region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.142 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -2.94 | |
| Confidence Interval |
(2-Sided) 95% -6.92 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left lower region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.757 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.83 | |
| Confidence Interval |
(2-Sided) 95% -6.26 to 4.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right whole region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.500 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.27 | |
| Confidence Interval |
(2-Sided) 95% -5.03 to 2.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left whole region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.353 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.93 | |
| Confidence Interval |
(2-Sided) 95% -6.09 to 2.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of whole region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.438 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -1.52 | |
| Confidence Interval |
(2-Sided) 95% -5.43 to 2.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Cumulative Frequency of HU |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 16 |
| Right Upper (n= 23, 16) |
4429363
(1696731)
|
4596228
(1012400)
|
| Right Middle (n= 23, 16) |
1474625
(409858)
|
1500073
(644286)
|
| Right Lower (n= 23, 16) |
4507375
(1302992)
|
4498652
(1703957)
|
| Left Upper (n= 23, 16) |
4818524
(1541192)
|
5105606
(1574676)
|
| Left Lower (n= 23, 16) |
4351407
(1677740)
|
4392819
(1256283)
|
| Right Whole (n= 23, 16) |
10411363
(2651975)
|
10594953
(2678348)
|
| Left Whole (n= 23, 16) |
9169931
(2630471)
|
9498425
(2471947)
|
| Whole Lung (n= 23, 16) |
19581293
(5212292)
|
20093377
(5022730)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right upper region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.220 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 351487 | |
| Confidence Interval |
(2-Sided) 95% -219976 to 922951 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right middle region of the lung at Week 104 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.146 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 103036 | |
| Confidence Interval |
(2-Sided) 95% -37651 to 243723 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right lower region of the lung at Week 104 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.322 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 247358 | |
| Confidence Interval |
(2-Sided) 95% -252728 to 747444 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left upper region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.141 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 362384 | |
| Confidence Interval |
(2-Sided) 95% -126518 to 851286 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left lower region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.325 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 294202 | |
| Confidence Interval |
(2-Sided) 95% -303329 to 891733 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right whole region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.258 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 575882 | |
| Confidence Interval |
(2-Sided) 95% -439692 to 1591457 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left whole region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.247 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 589373 | |
| Confidence Interval |
(2-Sided) 95% -426928 to 1605673 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of whole lung region of the lung at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.251 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 1156318 | |
| Confidence Interval |
(2-Sided) 95% -855009 to 3167645 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV]) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 22 | 16 |
| Right Upper (RV) (n= 22, 16) |
31.4
(145.3)
|
-64.3
(216.5)
|
| Right Middle (RV) (n= 22, 16) |
-14.1
(65.7)
|
-8.6
(63.6)
|
| Right Lower (RV) (n= 22, 16) |
18.1
(186.2)
|
-49.3
(254.8)
|
| Left Upper (RV) (n= 22, 16) |
11.0
(153.8)
|
-72.9
(212.9)
|
| Left Lower (RV) (n= 22, 16) |
13.0
(216.2)
|
-52.8
(220.7)
|
| Right Whole (RV) (n= 22, 16) |
35.3
(350.7)
|
-122.1
(504.5)
|
| Left Whole (RV) (n= 22, 16) |
23.8
(352.0)
|
-125.6
(401.8)
|
| Whole Lung (RV) (n= 22, 16) |
59.4
(693.3)
|
-247.8
(894.2)
|
| Right Upper (TLC) (n= 22, 16) |
-0.7
(173.9)
|
-52.3
(144.5)
|
| Right Middle (TLC) (n= 22, 16) |
3.7
(71.2)
|
-6.1
(62.6)
|
| Right Lower (TLC) (n= 22, 16) |
-12.5
(215.2)
|
-18.1
(159.2)
|
| Left Upper (TLC) (n= 22, 16) |
1.0
(141.8)
|
-59.1
(139.2)
|
| Left Lower (TLC) (n= 22, 16) |
-6.9
(270.2)
|
-35.8
(195.6)
|
| Right Whole (TLC) (n= 22, 16) |
-9.2
(341.0)
|
-76.3
(291.0)
|
| Left Whole (TLC) (n= 22, 16) |
-6.1
(390.6)
|
-95.1
(320.9)
|
| Whole Lung (TLC) (n= 22, 16) |
-15.2
(711.3)
|
-171.4
(584.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right upper lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.181 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 77.9 | |
| Confidence Interval |
(2-Sided) 95% -38.0 to 193.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right middle lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.781 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -5.9 | |
| Confidence Interval |
(2-Sided) 95% -48.8 to 36.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right lower lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.445 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 47.7 | |
| Confidence Interval |
(2-Sided) 95% -77.8 to 173.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left upper lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.259 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 62.6 | |
| Confidence Interval |
(2-Sided) 95% -48.1 to 173.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left lower lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.639 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 32.0 | |
| Confidence Interval |
(2-Sided) 95% -105.6 to 169.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right whole lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.408 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 102.3 | |
| Confidence Interval |
(2-Sided) 95% -145.9 to 350.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left whole lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.445 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 85.2 | |
| Confidence Interval |
(2-Sided) 95% -138.8 to 309.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of whole lung region (RV) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.421 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 187.6 | |
| Confidence Interval |
(2-Sided) 95% -279.6 to 654.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right upper lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.353 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 50.7 | |
| Confidence Interval |
(2-Sided) 95% -58.5 to 159.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right middle lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.660 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 9.9 | |
| Confidence Interval |
(2-Sided) 95% -35.3 to 55.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right lower lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.859 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 10.7 | |
| Confidence Interval |
(2-Sided) 95% -110.7 to 132.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left upper lung region (TLC)at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.253 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 51.5 | |
| Confidence Interval |
(2-Sided) 95% -38.4 to 141.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left lower lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.754 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 23.3 | |
| Confidence Interval |
(2-Sided) 95% -126.0 to 172.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of right whole lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.546 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 62.2 | |
| Confidence Interval |
(2-Sided) 95% -145.1 to 269.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of left whole lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.554 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 64.9 | |
| Confidence Interval |
(2-Sided) 95% -155.5 to 285.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis of whole lung region (TLC) at Week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.524 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 132.2 | |
| Confidence Interval |
(2-Sided) 95% -284.9 to 549.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Trough RV/TLC |
|---|---|
| Description | Change from Baseline in Trough RV/TLC is presented in the below outcome data table. |
| Time Frame | Baseline to Week 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 21 | 14 |
| Mean (Standard Deviation) [unitless] |
0.01
(0.12)
|
0.01
(0.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5843 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.07 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Trough Inspiratory Capacity |
|---|---|
| Description | Change from Baseline in Trough Inspiratory Capacity is presented in the below outcome data table. |
| Time Frame | Baseline toWeek 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 25 | 14 |
| Mean (Standard Deviation) [mL] |
0.074
(0.574)
|
-0.225
(0.384)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1252 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.249 | |
| Confidence Interval |
(2-Sided) 95% -0.073 to 0.571 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth) |
|---|---|
| Description | Change from baseline in trough FRCpleth is presented in the below outcome data table. |
| Time Frame | Baseline to Week 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 15 |
| Mean (Standard Deviation) [mL] |
-0.010
(1.0130)
|
0.029
(0.5290)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4661 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.1835 | |
| Confidence Interval |
(2-Sided) 95% -0.6892 to 0.3221 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco) |
|---|---|
| Description | Change from Baseline in DLco is presented in the below outcome data table. |
| Time Frame | Baseline to Week 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 15 |
| Mean (Standard Deviation) [mmoL/min/kPA] |
0.021
(0.8485)
|
-0.625
(1.6288)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.134 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.60 | |
| Confidence Interval |
(2-Sided) 95% -0.19 to 1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw) |
|---|---|
| Description | Change from baseline in sRaw and sGaw is presented in the below outcome data table. |
| Time Frame | Baseline to Week 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 23 | 15 |
| sRaw |
-0.29
(1.110)
|
0.47
(1.387)
|
| sGaw |
0.11
(0.584)
|
-0.07
(0.293)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for sRaw | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.074 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.71 | |
| Confidence Interval |
(2-Sided) 95% -1.50 to 0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for sGaw | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.155 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.22 | |
| Confidence Interval |
(2-Sided) 95% -0.09 to 0.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 13 | 9 |
| Mean prior daily breath symptoms (n= 13, 9) |
0.13
(0.60)
|
0.20
(0.95)
|
| Mean prior daily cough symptoms (n= 13, 9) |
0.10
(0.40)
|
-0.13
(1.13)
|
| Mean prior daily sputum symptoms (n= 13, 9) |
0.15
(0.74)
|
0.31
(1.07)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for mean prior daily breath symptoms | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.845 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.07 | |
| Confidence Interval |
(2-Sided) 95% -0.77 to 0.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for mean prior daily cough symptoms | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.549 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.21 | |
| Confidence Interval |
(2-Sided) 95% -0.52 to 0.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for mean prior daily sputum symptoms | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.717 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -0.93 to 0.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications |
|---|---|
| Description | Participants recorded rescue medication use (albuterol and/or ipratropium bromide) in a rescue medication log. |
| Time Frame | Baseline to Week 104 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 14 | 9 |
| Mean (Standard Deviation) [number of puffs] |
-0.74
(1.57)
|
-2.52
(3.82)
|
| Title | Percentage of Participants With COPD Exacerbations by Group at Week 104 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 48 | 28 |
| Level I (Baseline) (n= 48, 28) |
0.0
0%
|
0.0
0%
|
| Level I (Week 104) (n= 23, 15) |
4.3
8.4%
|
6.7
20.3%
|
| Level II (Baseline) (n= 48, 28) |
0.0
0%
|
0.0
0%
|
| Level II (Week 104) (n= 23, 15) |
8.7
17.1%
|
6.7
20.3%
|
| Level III (Baseline) (n= 48, 28) |
0.0
0%
|
0.0
0%
|
| Level III (Week 104) (n= 23, 15) |
8.7
17.1%
|
0.0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for level I (self management) at week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for level II (physician visit) at week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis for level III (hospital visit) at week 104. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5092 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Tetomilast 50 mg | Placebo |
|---|---|---|
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) |
| Measure Participants | 48 | 28 |
| Level 2 or Higher (Baseline) |
0.0
0%
|
0.0
0%
|
| Level 1 or No Exacerbation (Baseline) |
100.0
196.1%
|
100.0
303%
|
| Level 2 or Higher (Week 104) |
8.3
16.3%
|
3.6
10.9%
|
| Level 1 or No Exacerbation (Week 104) |
39.6
77.6%
|
50.0
151.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Tetomilast 50 mg, Placebo |
|---|---|---|
| Comments | Statistical analysis at Week 104 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.630 |
| Comments | Fisher's Exact test was used to determine whether the tetomilast and placebo groups differ in the proportion of participants who experienced Level 2 or higher COPD exacerbations during the study. | |
| Method | Fisher Exact | |
| Comments | ||
Adverse Events
| Time Frame | Adverse events were reported from the signing of the informed consent, throughout the 104 week treatment period until the follow-up visit of 14 (+2) days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Tetomilast 25 mg | Placebo | ||
| Arm/Group Description | Participants were administered oral tetomilast 25 milligram (mg) once daily for 2 weeks followed by 50 mg once daily for 102 weeks. | Participants were administered matching placebo for 104 weeks (2 years) | ||
All Cause Mortality |
||||
| Tetomilast 25 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Tetomilast 25 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/51 (25.5%) | 12/33 (36.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 0/51 (0%) | 1/33 (3%) | ||
| Cardiac disorders | ||||
| Angina unstable | 0/51 (0%) | 1/33 (3%) | ||
| Coronary artery stenosis | 0/51 (0%) | 1/33 (3%) | ||
| Gastrointestinal disorders | ||||
| Colitis | 0/51 (0%) | 2/33 (6.1%) | ||
| Abdominal pain | 1/51 (2%) | 0/33 (0%) | ||
| Abdominal pain upper | 0/51 (0%) | 1/33 (3%) | ||
| Duodenal ulcer | 1/51 (2%) | 0/33 (0%) | ||
| Duodenal ulcer haemorrhage | 0/51 (0%) | 1/33 (3%) | ||
| Dysphagia | 1/51 (2%) | 0/33 (0%) | ||
| Erosive duodenitis | 1/51 (2%) | 0/33 (0%) | ||
| Ileus | 0/51 (0%) | 1/33 (3%) | ||
| Inguinal hernia, obstructive | 1/51 (2%) | 0/33 (0%) | ||
| Large intestinal stenosis | 0/51 (0%) | 1/33 (3%) | ||
| Melaena | 1/51 (2%) | 0/33 (0%) | ||
| Nausea | 1/51 (2%) | 0/33 (0%) | ||
| Vomiting | 1/51 (2%) | 0/33 (0%) | ||
| General disorders | ||||
| Non-cardiac chest pain | 2/51 (3.9%) | 0/33 (0%) | ||
| Hepatobiliary disorders | ||||
| Bile duct stenosis | 1/51 (2%) | 0/33 (0%) | ||
| Biliary colic | 0/51 (0%) | 1/33 (3%) | ||
| Infections and infestations | ||||
| Pneumonia | 2/51 (3.9%) | 3/33 (9.1%) | ||
| Lobar Pneumonia | 2/51 (3.9%) | 0/33 (0%) | ||
| Cellulitis | 0/51 (0%) | 1/33 (3%) | ||
| Clostridium difficile colitis | 1/51 (2%) | 0/33 (0%) | ||
| Colostomy infection | 0/51 (0%) | 1/33 (3%) | ||
| Corona virus infection | 0/51 (0%) | 1/33 (3%) | ||
| Diverticulitis | 0/51 (0%) | 1/33 (3%) | ||
| Influenza | 1/51 (2%) | 0/33 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Carotid artery restenosis | 0/51 (0%) | 1/33 (3%) | ||
| Procedural headache | 1/51 (2%) | 0/33 (0%) | ||
| Toxicity to various agents | 0/51 (0%) | 1/33 (3%) | ||
| Investigations | ||||
| Hepatic enzyme increased | 0/51 (0%) | 1/33 (3%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Lung adenocarcinoma | 0/51 (0%) | 1/33 (3%) | ||
| Lung neoplasm malignant | 1/51 (2%) | 0/33 (0%) | ||
| Metastatic neoplasm | 1/51 (2%) | 0/33 (0%) | ||
| Nervous system disorders | ||||
| Ischaemic cerebral infarction | 1/51 (2%) | 0/33 (0%) | ||
| Psychiatric disorders | ||||
| Psychotic disorder | 0/51 (0%) | 1/33 (3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstrutive pulmonary disease | 6/51 (11.8%) | 4/33 (12.1%) | ||
| Dyspnoea | 1/51 (2%) | 1/33 (3%) | ||
| Respiratory failure | 2/51 (3.9%) | 0/33 (0%) | ||
| Atelectasis | 1/51 (2%) | 0/33 (0%) | ||
| Pleural effusion | 1/51 (2%) | 0/33 (0%) | ||
| Pneumothorax | 1/51 (2%) | 0/33 (0%) | ||
| Pulmonary embolism | 1/51 (2%) | 0/33 (0%) | ||
| Vascular disorders | ||||
| Aortic aneurysm | 1/51 (2%) | 0/33 (0%) | ||
| Deep vein thrombosis | 1/51 (2%) | 0/33 (0%) | ||
| Peripheral arterial occlusive disease | 1/51 (2%) | 0/33 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Tetomilast 25 mg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 30/51 (58.8%) | 23/33 (69.7%) | ||
| Blood and lymphatic system disorders | ||||
| Leukocytosis | 0/51 (0%) | 2/33 (6.1%) | ||
| Cardiac disorders | ||||
| Palpitations | 0/51 (0%) | 2/33 (6.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/51 (5.9%) | 2/33 (6.1%) | ||
| Constipation | 1/51 (2%) | 2/33 (6.1%) | ||
| Diarrhoea | 5/51 (9.8%) | 2/33 (6.1%) | ||
| Gastritis | 3/51 (5.9%) | 0/33 (0%) | ||
| Gastrooesophageal reflux disease | 1/51 (2%) | 2/33 (6.1%) | ||
| Nausea | 3/51 (5.9%) | 1/33 (3%) | ||
| General disorders | ||||
| Pyrexia | 0/51 (0%) | 2/33 (6.1%) | ||
| Infections and infestations | ||||
| Bronchitis | 5/51 (9.8%) | 6/33 (18.2%) | ||
| Gastroenteritis viral | 0/51 (0%) | 2/33 (6.1%) | ||
| Sinusitis | 2/51 (3.9%) | 3/33 (9.1%) | ||
| Upper respiratory tract infection | 5/51 (9.8%) | 3/33 (9.1%) | ||
| Urinary tract infection | 3/51 (5.9%) | 3/33 (9.1%) | ||
| Investigations | ||||
| Weight decreased | 0/51 (0%) | 2/33 (6.1%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/51 (0%) | 3/33 (9.1%) | ||
| Hypokalemia | 0/51 (0%) | 2/33 (6.1%) | ||
| Hyponatraemia | 0/51 (0%) | 2/33 (6.1%) | ||
| Nervous system disorders | ||||
| Headache | 1/51 (2%) | 2/33 (6.1%) | ||
| Psychiatric disorders | ||||
| Anxiety | 2/51 (3.9%) | 2/33 (6.1%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 3/51 (5.9%) | 0/33 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstrictive pulmonary disease | 16/51 (31.4%) | 13/33 (39.4%) | ||
| Cough | 4/51 (7.8%) | 3/33 (9.1%) | ||
| Dyspnoea | 0/51 (0%) | 2/33 (6.1%) | ||
| Respiratory tract congestion | 0/51 (0%) | 2/33 (6.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Ecchymosis | 0/51 (0%) | 2/33 (6.1%) | ||
| Vascular disorders | ||||
| Hypertension | 3/51 (5.9%) | 2/33 (6.1%) | ||
Limitations/Caveats
This trial was terminated early, not due to a safety concern, but due to a business decision to cease development of the tetolimast clinical program.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Global Medical Affairs |
|---|---|
| Organization | Otsuka Pharmaceutical Development and Commercialization, Inc. |
| Phone | 800 562-3974 |
Responsible Party:
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00874497
Other Study ID Numbers:
- 197-08-250
First Posted:
Apr 2, 2009
Last Update Posted:
Apr 17, 2017
Last Verified:
Mar 1, 2017