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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tetomilast
placebo
Sponsored by
Otsuka Pharmaceutical Development & Commercialization, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease

Eligibility Criteria

40 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UAB Lung Health Center
  • Los Angeles Biomedical Institute
  • Pulmonary Disease Specialist/PDS Research
  • Well Pharma Medical Research
  • Florida Premier Research Institute
  • Georgia Clinical Research
  • Illinios Lung Institute
  • University of Louisville, Pulmonary Division
  • University of Nebraska Medical Center
  • Temple University Hospital
  • Spartanburg Medical Research
  • Texas Institute of Chest and Sleep Disorders, PA
  • Diagnostics Research Group
  • Pulmonary Associates of Richmond
  • Multicare Pulmonary Specialist

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1 Tetomilast

2 Placebo

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1)
The analysis of the change from Baseline to Week 104 (last observation carried forward [LOCF]) in trough FEV1 is presented below.
Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels
The analysis of the change from Baseline to Week 104 (LOCF) in the 20th percentile of lung density voxels (expressed in Hounsfield unit [HU] using quantitative HCRT) by visit and lung region is presented below.

Secondary Outcome Measures

Percent Change From Baseline in Trough FEV1 From Baseline to Week 104
The percent change for the pulmonary function tests (PFT) from baseline was calculated for each study week as follows: % change from baseline = ([value at Week X - value at baseline] /value at baseline) x 100.
Density Mask Score Based on Specified Thresholds Including -950 HU
The density mask score is defined as the percentage of lung density voxels that lie below a specified threshold in the lung region of interest. The higher the percentage of the participant's lung density voxels that lie below a specified threshold, the higher the level of the participant's emphysema in the lung region under consideration. Changes in the density mask score was assessed using only a single density mask threshold of -950 HU.
Rate of Change in the 20th Percentile of Lung Density Voxels Expressed in HU Units for the Whole Lung (Whole Right + Whole Left) From Baseline to Week 104
The rate of change in lung density was calculated as the change in the 20th percentile of lung density voxels divided by the duration between the dates of measurement (month or year) where applicable. For example, if HRCT measurements are available over a span of 2 years, the annual rate of change was calculated as the difference over the 2 years divided by 2, where years between scans is given by years= floor(data of last scan - date of first scan + 1)/365.25.
Observed Rate of Change in Emphysema From Baseline to Week 104
The level of emphysema (g/L) within in a lung region is defined as the value of the selected percentile (10th, 15th, or 20th) in HU + 1000. The rate of change in the emphysema from baseline was calculated as the change in the level of emphysema from baseline to the specified visit divided by the time in years between the baseline and specified visit (i.e., [date of visit - date of baseline visit + 1]/365.25).
Change From Baseline to Week 104 in Cumulative Frequency of HU
The area under the curve (AUC) is defined as the cumulative voxel frequency in HU (ie, the value of the density mask denominator). Blood samples (4 mL) for pharmacokinetic analysis were collected for the determination of plasma OPC-6535 concentrations at Predose on Day 1 and Weeks 26, 52, 78 and 104.
Change From Baseline to Week 104 in Computed Tomography (CT) - Derived Lung Volumes (Total Lung Capacity [TLC] and Residual Volume [RV])
Change from baseline in CT-derived lung volumes TLC and RV are presented in the below outcome data table.
Change From Baseline to Week 104 in Trough RV/TLC
Change from Baseline in Trough RV/TLC is presented in the below outcome data table.
Change From Baseline to Week 104 in Trough Inspiratory Capacity
Change from Baseline in Trough Inspiratory Capacity is presented in the below outcome data table.
Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth)
Change from baseline in trough FRCpleth is presented in the below outcome data table.
Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco)
Change from Baseline in DLco is presented in the below outcome data table.
Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw)
Change from baseline in sRaw and sGaw is presented in the below outcome data table.
Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum
Participants used the Breathlessness, Cough, and Sputum Scale (BCSS) as the diary to daily monitor and rate their symptoms of difficulty breathing, cough, and sputum. The scale allows patients to rate each symptom on a scale of 0 (no difficultly for breathing and sputum, or unaware of coughing) to 4 (an almost constant problem for breathing and sputum, or almost constant for cough).
Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications
Participants recorded rescue medication use (albuterol and/or ipratropium bromide) in a rescue medication log.
Percentage of Participants With COPD Exacerbations by Group at Week 104
For the COPD exacerbations, baseline is defined as Randomization (Day 1). COPD exacerbations, defined as an acute worsening of COPD symptoms, were classified as being in one of 3 levels: Level I (can by self-managed by the participant); Level II (requires a physician visit), or Level III (requires a hospital visit).
Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher)
Percentage of participants experiencing a COPD exacerbation in a level 2 or higher are presented in the below outcome data table.

Full Information

First Posted
March 31, 2009
Last Updated
March 3, 2017
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00874497
Brief Title
Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema
Acronym
EMPHASIS
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 Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Sponsor Terminated
Study Start Date
March 2009 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1 Tetomilast
Arm Type
Experimental
Arm Title
2 Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
tetomilast
Intervention Description
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Placebo for 104 weeks (2 years)
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
UAB Lung Health Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Los Angeles Biomedical Institute
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Pulmonary Disease Specialist/PDS Research
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Facility Name
Well Pharma Medical Research
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Florida Premier Research Institute
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32789
Country
United States
Facility Name
Georgia Clinical Research
City
Austell
State/Province
Georgia
ZIP/Postal Code
30106
Country
United States
Facility Name
Illinios Lung Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
University of Louisville, Pulmonary Division
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Spartanburg Medical Research
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Texas Institute of Chest and Sleep Disorders, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
Diagnostics Research Group
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Pulmonary Associates of Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23225
Country
United States
Facility Name
Multicare Pulmonary Specialist
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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