Pilot Study of Tetomilast in Chronic Obstructive Pulmonary Disease (COPD) Associated With Emphysema (EMPHASIS)
3 mars 2017 mis à jour par: Otsuka Pharmaceutical Development & Commercialization, Inc.
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.
Aperçu de l'étude
Statut
Résilié
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
84
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
-
-
Alabama
-
Birmingham, Alabama, États-Unis, 35294
- UAB Lung Health Center
-
-
California
-
Torrance, California, États-Unis, 90502
- Los Angeles Biomedical Institute
-
-
Florida
-
Kissimmee, Florida, États-Unis, 34741
- Pulmonary Disease Specialist/PDS Research
-
Miami, Florida, États-Unis, 33143
- Well Pharma Medical Research
-
Winter Park, Florida, États-Unis, 32789
- Florida Premier Research Institute
-
-
Georgia
-
Austell, Georgia, États-Unis, 30106
- Georgia Clinical Research
-
-
Illinois
-
Peoria, Illinois, États-Unis, 61606
- Illinios Lung Institute
-
-
Kentucky
-
Louisville, Kentucky, États-Unis, 40202
- University of Louisville, Pulmonary Division
-
-
Nebraska
-
Omaha, Nebraska, États-Unis, 68198
- University of Nebraska Medical Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, États-Unis, 19140
- Temple University Hospital
-
-
South Carolina
-
Spartanburg, South Carolina, États-Unis, 29303
- Spartanburg Medical Research
-
-
Texas
-
Houston, Texas, États-Unis, 77034
- Texas Institute of Chest and Sleep Disorders, PA
-
San Antonio, Texas, États-Unis, 78229
- Diagnostics Research Group
-
-
Virginia
-
Richmond, Virginia, États-Unis, 23225
- Pulmonary Associates of Richmond
-
-
Washington
-
Tacoma, Washington, États-Unis, 98405
- Multicare Pulmonary Specialist
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
40 ans à 75 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Tripler
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur placebo: 2 Placebo
|
Placebo for 104 weeks (2 years)
|
|
Expérimental: 1 Tetomilast
|
Oral tetomilast 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 years.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Change From Baseline to Week 104 in Trough Forced Expiratory Volume in 1 Second (FEV1)
Délai: 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.
|
Baseline to Week 104
|
|
Rate of Change From Baseline to Week 104 in 20th Percentile of Lung Density Voxels
Délai: 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.
|
Baseline to Week 104
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percent Change From Baseline in Trough FEV1 From Baseline to Week 104
Délai: 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.
|
Baseline to Week 104
|
|
Density Mask Score Based on Specified Thresholds Including -950 HU
Délai: 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.
|
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
Délai: 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.
|
Baseline to Week 104
|
|
Observed Rate of Change in Emphysema From Baseline to Week 104
Délai: 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).
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in Cumulative Frequency of HU
Délai: 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.
|
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])
Délai: Baseline to Week 104
|
Change from baseline in CT-derived lung volumes TLC and RV are presented in the below outcome data table.
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in Trough RV/TLC
Délai: Baseline to Week 104
|
Change from Baseline in Trough RV/TLC is presented in the below outcome data table.
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in Trough Inspiratory Capacity
Délai: Baseline toWeek 104
|
Change from Baseline in Trough Inspiratory Capacity is presented in the below outcome data table.
|
Baseline toWeek 104
|
|
Change From Baseline to Week 104 in Trough Functional Residual Capacity (FRCpleth)
Délai: Baseline to Week 104
|
Change from baseline in trough FRCpleth is presented in the below outcome data table.
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in Carbon Monoxide Diffusion Capacity (DLco)
Délai: Baseline to Week 104
|
Change from Baseline in DLco is presented in the below outcome data table.
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in Mean Specific Airway Resistance (sRaw) and Specific Conductance (sGaw)
Délai: Baseline to Week 104
|
Change from baseline in sRaw and sGaw is presented in the below outcome data table.
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in 7-day Average Total Symptom Score of Dyspnea, Cough and Sputum
Délai: 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).
|
Baseline to Week 104
|
|
Change From Baseline to Week 104 in 7-day Mean Number of Actuations of Rescue Medications
Délai: Baseline to Week 104
|
Participants recorded rescue medication use (albuterol and/or ipratropium bromide) in a rescue medication log.
|
Baseline to Week 104
|
|
Percentage of Participants With COPD Exacerbations by Group at Week 104
Délai: 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).
|
Baseline and Week 104
|
|
Percentage of Participants Experiencing a COPD Exacerbation (Level 2 or Higher)
Délai: 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.
|
Baseline and Week 104
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mars 2009
Achèvement primaire (Réel)
1 juillet 2015
Achèvement de l'étude (Réel)
1 août 2015
Dates d'inscription aux études
Première soumission
31 mars 2009
Première soumission répondant aux critères de contrôle qualité
1 avril 2009
Première publication (Estimation)
2 avril 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
17 avril 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
3 mars 2017
Dernière vérification
1 mars 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 197-08-250
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .