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Trial record 1 of 1 for:    NCT00874497
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Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema (EMPHASIS)

This study has been terminated.
(Sponsor Terminated)
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00874497
First received: March 31, 2009
Last updated: March 3, 2017
Last verified: March 2017
  Purpose
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.

Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: tetomilast
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 84
Study Start Date: March 2009
Study Completion Date: August 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874497

Locations
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
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00874497     History of Changes
Other Study ID Numbers: 197-08-250
Study First Received: March 31, 2009
Results First Received: August 23, 2016
Last Updated: March 3, 2017

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Emphysema
Respiratory Tract Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 23, 2017