Chronic Obstructive Pulmonary Disease (COPD) With Cachexia Clinical Trial
Official title:
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.
| Status | Completed |
| Enrollment | 67 |
| Est. completion date | December 2014 |
| Est. primary completion date | December 2014 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | Both |
| Age group | 40 Years to 80 Years |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | Novartis Investigative Site | Maastricht | |
| United Kingdom | Novartis Investigative Site | Leicester | |
| United Kingdom | Novartis Investigative Site | London | |
| United Kingdom | Novartis Investigative Site | Machester | |
| United States | Novartis Investigative Site | Missoula | Montana |
| United States | Novartis Investigative Site | Normal | Illinois |
| United States | Novartis Investigative Site | Savannah | Georgia |
| United States | Novartis Investigative Site | Spartanburg | South Carolina |
| United States | Novartis Investigative Site | Torrance | California |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Netherlands, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 4, 8, 16, and 24 | Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 4,8,16 and 24 was considered responders. | Baseline, Weeks 4, 8, 16, 24 | No |
| Secondary | Change in 6 Minute Walk Distance Compared to Placebo | Practical simple test that requires a 100-ft hallway but no exercise quipment or advanced training for technicians. Walking is an activity performed daily by all but the most severely impaired patients. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD) | Baseline, Weeks 4, 8, 16, 24 | No |
| Secondary | Maximum Observed Serum Concentration (Cmax) | The observed maximum plasma concentration following drug administration | 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose | No |
| Secondary | Time to Reach the Maximum Concentration After Drug Administration (Tmax) | The time to reach the maximum concentration after drug administration | 24 weeks | No |
| Secondary | AUC0-56 and AUClast | AUC0-56, the area under the serum concentration-time curve from the time zero to the end of the dosing interval, day 56. AUC0-56 was analyzed for dose 1 and 2. AUClast is from time zero to the last quantifiable concentration. AUClast was analyzed for dose 2 only. | 0 hour, 2 hour, Day 8, 15, 29, 57, 71, 85, 99, 113, 127, 168 post dose | No |