Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema (EMPHASIS)
|ClinicalTrials.gov Identifier: NCT00874497|
Recruitment Status : Terminated (Sponsor Terminated)
First Posted : April 2, 2009
Results First Posted : April 17, 2017
Last Update Posted : April 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease||Drug: tetomilast Drug: placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||84 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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 :||March 2009|
|Primary Completion Date :||July 2015|
|Study Completion Date :||August 2015|
|Experimental: 1 Tetomilast||
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
|Placebo Comparator: 2 Placebo||
Placebo for 104 weeks (2 years)
- Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 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 [ Time Frame: 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.
- Percent Change From Baseline in Trough FEV1 From Baseline to Week 104 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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]) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00874497
|United States, Alabama|
|UAB Lung Health Center|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|Los Angeles Biomedical Institute|
|Torrance, California, United States, 90502|
|United States, Florida|
|Pulmonary Disease Specialist/PDS Research|
|Kissimmee, Florida, United States, 34741|
|Well Pharma Medical Research|
|Miami, Florida, United States, 33143|
|Florida Premier Research Institute|
|Winter Park, Florida, United States, 32789|
|United States, Georgia|
|Georgia Clinical Research|
|Austell, Georgia, United States, 30106|
|United States, Illinois|
|Illinios Lung Institute|
|Peoria, Illinois, United States, 61606|
|United States, Kentucky|
|University of Louisville, Pulmonary Division|
|Louisville, Kentucky, United States, 40202|
|United States, Nebraska|
|University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|United States, Pennsylvania|
|Temple University Hospital|
|Philadelphia, Pennsylvania, United States, 19140|
|United States, South Carolina|
|Spartanburg Medical Research|
|Spartanburg, South Carolina, United States, 29303|
|United States, Texas|
|Texas Institute of Chest and Sleep Disorders, PA|
|Houston, Texas, United States, 77034|
|Diagnostics Research Group|
|San Antonio, Texas, United States, 78229|
|United States, Virginia|
|Pulmonary Associates of Richmond|
|Richmond, Virginia, United States, 23225|
|United States, Washington|
|Multicare Pulmonary Specialist|
|Tacoma, Washington, United States, 98405|