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

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)
• Patients weighing ≥ 120 kg
• 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.
• Any other clinically relevant disease or disorder e.g., infectious/viral disease (including hepatitis B or C), cardiovascular (including unstable ischaemic heart disease, arrythmia, cardiomyopathy, uncontrolled hypertension), pulmonary disease other than COPD, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment, past or present, which in the opinion of the Investigator may either put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study.
• Diseases known to cause malabsorption of protein or energy, such as inflammatory bowel disease, celiac disease, short bowel syndrome, pancreatic insufficiency, etc.
• 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.
• Hospitalization within 14-days prior to screening
• Hemoglobin concentration below 11.0 g/dL at screening.
• Liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), γ-GT, alkaline phosphatase, or serum bilirubin (other than Gilbert's Disease). The Investigator should be guided by the following criteria: Any single transaminase listed above may not exceed 3x upper limit of normal (ULN); If the total bilirubin concentration is increased above 1.5 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. Total serum bilirubin should not exceed 2 x ULN.
• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
• Patients with known claustrophobia, double above-knee leg amputee, presence of pacemaker and/or ferromagnetic material in their body that would prohibit MRI imaging.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
• Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
• Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository In case of use of oral contraception women should have been stabile on the same pill for a minimum of 3 months before taking study treatment.

No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients.

Other protocol-defined inclusion/exclusion criteria may apply