BYM338 in Chronic Obstructive Pulmonary Disease (COPD) Patients With Cachexia

A Randomized, Double Blind, Placebo Controlled, Multi-centre Study to Asses the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of BYM338 in Chronic Obstructive Pulmonary Disease Patients With Cachexia

This study will assess the pharmacodynamics, pharmacokinetics, safety and tolerability of BYM338 in patients with COPD and cachexia. The primary outcome will be a change in thigh muscle volume compared to placebo. The study will last for approximately 24 weeks.

Inclusion criteria:

• Written informed consent must be obtained before any assessment is performed.
• Males and females ages 40 to 80 years
• Smoking history of at least 10 pack-years
• Diagnosis of COPD according to GOLD guidelines (GOLD, 2010), with a post-bronchodilator FEV¬1 < 80% predicted and FEV1/FVC ratio < 0.70
• BMI <20 kg/m2 or skeletal muscle mass index by DXA < 7.25 kg/m2 for men or <5.45 kg/m2 for women.
• In general stable health, including managed COPD, by past medical history, physical examination, vital signs at baseline as determined by the investigator.

Exclusion criteria:

• Patients with MRC dyspnoea grade 5 (i.e. patients too breathless to leave the house or breathless when dressing)
• Plans for lung transplantation or lung reduction surgery within four months of enrollment
• Patients participating in a formal pulmonary rehabilitation program within 3 months of dosing
• History of malignancy of any organ system (other than excised non-melanomatous carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Diseases other than cancer known to cause cachexia or muscle atrophy, including but not limited to congestive heart failure of any stage, chronic kidney disease (estimated GFR < 30 mL/min using the MDRD equation), rheumatoid arthritis, primary myopathy, stroke, HIV infection, tuberculosis or other chronic infection, uncontrolled diabetes mellitus, etc.
• Inflammatory bowel disease, celiac disease, short bowel syndrome, pancreatic insufficiency
• Use of any prescription drugs known to affect muscle mass, including androgen supplements, anti-androgens (such as LHRH agonists), anti-estrogens (tamoxifen, etc.) recombinant human growth hormone (rhGH), insulin, oral beta agonists, megestrol acetate, dronabinol, metformin, etc.
• Hemoglobin concentration below 11.0 g/dL at screening.
• Liver disease or liver injury.
• Use of other investigational drugs at the time of enrollment, or within 30 days and for any other limitation of participation in an investigational trial based on local regulations.
• Women of child-bearing potential.

Other protocol-defined inclusion/exclusion criteria may apply