Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 12.1 Level: LLT Classification code 10009033 Term: Chronic obstructive pulmonary disease
Conditions
Interventions
Product Name: Losmapimod
Product Code: GW856553
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Losmapimod
Current Sponsor code: GW856553
Concentration unit: mg milligram(s)
Concentration
Sponsors
GlaxoSmithKline Research & Development
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]. 2. Severity of Disease: • Subjects with a measured post-salbutamol/albuterol FEV1/FVC ratio of =0.70 at Screening (Visit 1) [Pelligrino, 2005] • Subjects with a measured post-salbutamol/albuterol FEV1 40 years of age at Screening (Visit 1). (Contraceptive conditions apply) 5. Tobacco use: Subjects with a current or prior history of ?10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. One pack year = 20 cigarettes smoked per day for 1 year or the equivalent. Number of pack years = (number of cigarettes per day/20) x number of years smoked 6. Liver criteria: Subjects with the following liver function test values: • aspartate transaminase (AST) or alanine transaminase (ALT) 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnancy: Women who are pregnant or lactating or are planning to become pregnant during the study. 2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD). 3. ?1-antitrypsin deficiency: Subjects with ?1-antitrypsin deficiency as the underlying cause of COPD. 4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. Subjects with allergic rhinitis are not excluded. 5. Lung resection: Subjects who have undergone lung resection surgery (e.g., lung volume reduction surgery or lobectomy). 6. Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Screening (Visit 1) if a chest X-ray or CT scan is not available within 12 months prior to Visit 1. For sites in Germany, if a chest X-ray (or CT scan) is not available in the 12 months preceding Screening (Visit1), the subject will not be eligible for the study. 7. Recent exacerbation of COPD: Subjects with poorly controlled COPD which required the use of antibiotics, systemic corticosteroids and/or emergency treatment or hospitalisation within 12 weeks prior to Visit 1. 8. Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 12 weeks prior to Visit 1. 9. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., ?12 hours per day) is not exclusionary. 10. Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or other non-invasive positive pressure ventilation (NIPPV) device. 11. Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 12 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study. 12. Other diseases/abnormalities: Any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. 13. Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not exclude a subject if it has been considered cured within 5 years since diagnosis. 14. Liver: Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 15. Hepatitis: A positive Hepatitis B surface antigen or positive Hepatitis C antibody at Screening (Visit 1). 16. Obesity: Subjects who have a Body Mass Index (BMI) > 35. 17. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g., lactose, magnesium stearate). 18. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years. 19. Medication prior to spirometry: Subjects who are medically unable to withhold their salbut
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to evaluate the efficacy, dose response, safety, tolerability and PK of three doses of losmapimod (2.5mg, 7.5mg and 15mg) administered twice daily compared with placebo in subjects with COPD. The study will evaluate primarily the effects of each dose on exercise tolerance, as assessed by the six-minute walk distance (6MWD).;Secondary Objective: The study will also measure the effects on exacerbations, quality of life, lung function, systemic inflammation and safety.;Primary end point(s): Change in Six minute walk distance (6MWD) | — |
Countries
Czech Republic, Estonia, Germany
Outcome results
None listed