Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema (EMPHASIS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Tracking Information
First Submitted Date  ICMJE March 31, 2009
First Posted Date  ICMJE April 2, 2009
Results First Submitted Date  ICMJE August 23, 2016
Results First Posted Date  ICMJE April 17, 2017
Last Update Posted Date April 17, 2017
Study Start Date  ICMJE March 2009
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
The change in trough forced expiratory volume in 1 second (FEV1) and the rate of change in the 20th percentile of lung density voxels using High Resolution Computed Tomography (HRCT) [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT00874497 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2009)
Percent change in trough FEV1 [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema
Official Title  ICMJE 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
Brief Summary Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Drug: tetomilast
    Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
  • Drug: placebo
    Placebo for 104 weeks (2 years)
Study Arms  ICMJE
  • Experimental: 1 Tetomilast
    Intervention: Drug: tetomilast
  • Placebo Comparator: 2 Placebo
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 26, 2015)
84
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2009)
100
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00874497
Other Study ID Numbers  ICMJE 197-08-250
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Sponsor  ICMJE Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Otsuka Pharmaceutical Development & Commercialization, Inc.
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP