Chronic Obstructive Pulmonary DiseasePhase 2EMPHASISNCT00874497
Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema
A Phase 2 study testing tetomilast in people with Chronic Obstructive Pulmonary Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 15 sites in United States.
Trial summary
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- tetomilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 15 sitesUnited States
- Study dates
- Mar 2009to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Georgia Clinical Research
Austell, Georgia, 30106
UAB Lung Health Center
Birmingham, Alabama, 35294
Texas Institute of Chest and Sleep Disorders, PA
Houston, Texas, 77034
Pulmonary Disease Specialist/PDS Research
Kissimmee, Florida, 34741
University of Louisville, Pulmonary Division
Louisville, Kentucky, 40202
Well Pharma Medical Research
Miami, Florida, 33143
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Illinios Lung Institute
Peoria, Illinois, 61606
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Pulmonary Associates of Richmond
Richmond, Virginia, 23225
Diagnostics Research Group
San Antonio, Texas, 78229
Spartanburg Medical Research
Spartanburg, South Carolina, 29303
Multicare Pulmonary Specialist
Tacoma, Washington, 98405
Los Angeles Biomedical Institute
Torrance, California, 90502
Florida Premier Research Institute
Winter Park, Florida, 32789
About this study
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
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- tetomilast, placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tetomilastDrug
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
placeboDrug
Placebo for 104 weeks (2 years)
| Study group | Role | What they receive |
|---|---|---|
| 1 Tetomilast | Experimental | Not described Receives: Drug: tetomilast |
| 2 Placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 104
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.
Measured: Baseline to Week 104
Secondary outcomes (15)
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.
Measured: Baseline to Week 104
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.
Measured: Baseline and Week 104
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.
Measured: Baseline to Week 104
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).
Measured: Baseline to Week 104
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.
Measured: Baseline and Week 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.
Measured: Baseline to Week 104
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.
Measured: Baseline to Week 104
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.
Measured: Baseline toWeek 104
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.
Measured: Baseline to Week 104
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.
Measured: Baseline to Week 104
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.
Measured: Baseline to Week 104
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).
Measured: Baseline to Week 104
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.
Measured: Baseline to Week 104
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).
Measured: Baseline and Week 104
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.
Measured: Baseline and Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2009 (estimated)
- Study startMar 2009
- Primary completionJul 2015
- Study completionAug 2015
Why it stopped: Sponsor Terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00874497
- Sponsor's protocol ID
- 197-08-250
- Acronym
- EMPHASIS
- Status last verified
- Mar 2017
- First submitted
- 31 Mar 2009
- Last updated
- 17 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00874497
- Acronym / sponsor ID
- EMPHASIS / 197-08-250
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Terminated
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 2 Apr 2009 (estimated)
- Results
- Posted 17 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 2a multicenter, randomized, double-blind, placebo-controlled study to assess the pharmacodynamics, efficacy, and safety of tetomilast in patients with emphysema.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Tetomilast | Experimental | Drug: tetomilast |
| 2 Placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tetomilastOral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years. | Drug | 1 Tetomilast |
| placeboPlacebo for 104 weeks (2 years) | Drug | 2 Placebo |
Primary outcome
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.
15 secondary outcomes
Percent Change From Baseline in Trough FEV1 From Baseline to Week 104
Time frame: Baseline to Week 104
Density Mask Score Based on Specified Thresholds Including -950 HU
Time frame: Baseline and Week 104
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
Observed Rate of Change in Emphysema From Baseline to Week 104
Time frame: Baseline to Week 104
Change From Baseline to Week 104 in Cumulative Frequency of HU
Time frame: Baseline and Week 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 to Week 104 in Trough RV/TLC
Time frame: Baseline to Week 104
Change From Baseline to Week 104 in Trough Inspiratory Capacity
Time frame: Baseline toWeek 104
Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth)
Time frame: Baseline to Week 104
Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco)
Time frame: Baseline to Week 104
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 to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum
Time frame: Baseline to Week 104
Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications
Time frame: Baseline to Week 104
Percentage of Participants With COPD Exacerbations by Group at Week 104
Time frame: Baseline and Week 104
Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher)
Time frame: Baseline and Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tetomilast in people with Chronic Obstructive Pulmonary Disease, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1) (time frame: Baseline to Week 104). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2017.