Chronic Obstructive Pulmonary Disease MedDRA version: 17.0 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Losmapimod
Product Code: GW856553
Pharmaceutical Form: Tablet
INN or Proposed INN: Losmapimod
CAS Number: 585543-15-3
Current Sponsor code: GW856553
Other descriptive name: GW856553X
Con
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. COPD diagnosis and severity: -Subjects with a clinical history of COPD (established by a physician) in accordance with the following definition by the American Thoracic Society/European Respiratory Society [Celli, 2004], for at least 6 months prior to enrolment. -Subjects must have evidence of airflow obstruction, defined as postbronchodilator FEV1 equal to or less than 80% of predicted normal value calculated using NHANES III reference equation at Visit 1 [Hankinson, 1999; Hankinson, 2010] and a FEV1 / FVC ratio 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory] or if of child-bearing potential is using a highly effective method for avoidance of pregnancy (refer to Section 4.3.1) from 30 days before the first dose, for the duration of dosing and until 2 weeks post last-dose. 6. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 7. QTc <450msec or QTc <480msec for subjects with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB), Fridericia’s formula (QTcF), or another method, machine or manual overread. -For eligibility and withdrawal, ideally the same QT correction formula will be used for all subjects. However, because this is not always possible, the same QT correction formula must be used fo
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 8. Eosinophils: > 2.0% blood eosinophils at Screening (Visit 1) 9. Concomitant medication: - COPD Medication: Subjects currently on chronic treatment with macrolides or Roflumilast; Long term oxygen therapy (LTOT) or nocturnal oxygentherapy required for greater than 12 hours a day. Oxygen PRN use (i.e. 2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 18. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 19. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Subjects that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded). 20. Other diseases/abnormalities: History or current evidence of clinically significant or uncontrolled cardiovascular, pulmonary, metabolic, neurological, endocrine (including uncontrolled diabetes or thyroid disease), renal, hepatic, haematological (including agranulocytosis) or gastrointestinal conditions that are uncontrolled on permitted therapy and in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study 21. Viral infec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the rate of COPD exacerbations in losmapimod compared to placebo treated subjects.;Secondary Objective: 1. To evaluate the time to first COPD exacerbation in subjects treated with losmapimod compared to placebo treated subjects. 2. To evaluate the effect of losmapimod treatment compared to placebo on additional parameters of lung function, in subjects with COPD. 3. To evaluate the safety and tolerability of losmapimod treatment compared to placebo, in subjects with COPD. 4. To evaluate the plasma PK of losmapimod in subjects with COPD. 5. To evaluate the use of rescue medication in subjects with COPD who are treated with losmapimod compared to placebo treated subjects. 6. To evaluate the health status of subjects with COPD who are treated with losmapimod compared to placebo treated subjects.;Primary end point(s): Yearly rate of moderate and severe exacerbations in both placebo and losmapimod treated groups.;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to first moderate-severe exacerbation. 2. Change from baseline in spirometry parameters over time including, but not limited to FEV1, FVC and FEV6. 3. Safety and tolerability parameters include: adverse events, clinical laboratory tests, electrocardiograms (ECGs), liver safety testing and vital signs. 4. AUC(0-t) [t=12h], Cmax, Ctrough 5. Frequency of short acting ?beta-agonist or anticholinergic use. 6. Change from baseline in SGRQ-C total and domain scores over time.;Timepoint(s) of evaluation of this end point: 1. End of study (Week 53) 2. End of study (Week 53) 3. End of study (Week 53) 4. Weeks 2, 12 and 26 5. End of study (Week 53) 6. Weeks 12, 26, 39 and 52. | — |
Countries
Argentina, Brazil, Bulgaria, Chile, Germany, Italy, Korea, Republic of, Slovakia, Spain
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed