Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 20.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Product Code: GSK2881078
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not available
CAS Number: 1539314-06-1
Current Sponsor code: GSK2881078A
Concentration unit: mg milligram(s)
Concentra
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must be 50 to 75 years of age inclusive, at the time of signing the informed consent. 2. Male and/or female: a. Male participants: A male participant with a partner who is a woman of child bearing potential (WOCPB) must agree to use contraception as detailed below during the treatment period and for at least 5 half-lives of study medication have passed after the last ingested dose [125 days, corresponding to time needed to eliminate study treatment for both genotoxic and teratogenic study treatments plus an additional 90 days (a spermatogenesis cycle) for study treatments with genotoxic potential] after the last dose of study treatment and refrain from donating sperm during this period. - Male participants with female partners of child-bearing potential are eligible to participate if they agree to ONE of the following during the protocol-defined time frame described above: - Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. - Agree to use a male condom plus an additional method of contraception with a failure rate of 60 years of age]. 3. Confirmed diagnosis of COPD in accordance with the ATS/ERS criteria with a post-bronchodilator FEV1/ forced vital capacity (FVC) < 0.70 AND 30%= FEV1% predicted =65% of predicted norm
Exclusion criteria
Exclusion criteria: 1. Participants with a history of myocardial infarction, angina, congestive heart failure exacerbation, hospitalization for cardiac aetiology, stroke or transient ischemic attack in the past 12 months. 2. Neurologic, musculoskeletal, osteoarthritis, or any other condition that in the opinion of the investigator limits participant’s ability to complete study physical assessments. 3. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 4. Participants with a history of cholecystectomy. 5. Participants with a history of malignancy that is not in complete remission for at least 2 years or 1 year for non-melanoma skin carcinoma. 6. Participants with a family history of early onset prostate cancer or familial prostate cancer (multiple family members). 7. Diseases known to cause malabsorption of protein or energy, such as inflammatory bowel disease, celiac disease, pancreatic insufficiency, etc. 8. Current or planned administration of cholestyramine or strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inducers. 9. Current or planned use of any prescription drugs known to affect muscle mass, including androgen supplements, anti-androgens (such as LHRH agonists), antiestrogens (tamoxifen, etc.), recombinant growth hormone, megesterol, etc. 10. Use of oral steroids concurrently or within 4 weeks preceding the screening visit. 11. The participant has participated in a clinical trial and has received an investigational product within the following time period prior to randomization in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 12. Participants with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study: •Renal function: Glomerular Filtration Rate (GFR) 7.5%. •ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 4.0 ng/mL 13. Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA PCR test is obtained. 14. QT interval corrected for heart rate by Bazett's formula or QT interval corrected for heart rate by Fridericia’s formula >450 msec or QT interval corrected for heart rate >480 msec in participants with Bundle Branch Block based on a single ECG. 15. A positive test for HIV antibody. 16. More than two moderate/severe COPD exacerbations within the past year •Exacerbation is defined as worsening of two or more of the following major symptoms: dyspnoea, sputum volume, sputum purulence OR worsening of any one major symptom together with at least one of the following additional symptoms: sore throat, colds (nasal discharge and/or nasal congestion), fever >37.5oC without any explained cause, increased cough, increased wheeze. •A moderate exacerbation is defined as an exacerbation that requires treatment with an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Assess the safety and tolerability of approximately 13 weeks of dosing of GSK2881078. - Assess the effect of approximately 13 weeks of doing of GSK2281078 on leg strength in older mean and postmenopausal women with COPD and muscle weakness, participating in home exercise.;Secondary Objective: - Assess the effect of approximately 13 weeks of dosing of GSK2281078 on lean soft tissue mass. - Assess the effect of approximately 13 weeks of dosing of GSK2881078 on exercise capacity. - Assess the effect of approximately 13 weeks of dosing of GSK2881078 on patient reported outcomes, levels or physical activity, activities of daily living and the patient perspective of efficacy. - Assess the effect of approximately 13 weeks of dosing on GSK2881078 on respiratory function. - Characterise the population pharmacokinetic (PK) profile of approximately 13 weeks of dosing of GSK2881078 in older men and post menopausal women with COPD and muscle weakness. ;Timepoint(s) of evaluation of this end point: -Throughout the duration of the study - At the end of the study ;Primary end point(s): - Safety and tolerability of GSK2881078 as assessed by clinical monitoring of blood pressure (BP), heart rate, electrocardiogram (ECG) and laboratory safety data, as well as reporting of adverse events (AEs). - % change from baseline and change from baseline in maximum leg press strength following 1 repetition maximum (1- RM). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline in appendicular, and total lean mass as assessed by Dual-energy X-ray Absorptiometry (DXA) - Change from baseline in total Short Physical Performance Battery (SPPB) score and times for chair and 4 m gait speed. - Change from baseline in Constant Work Rate (CWR) duration from endurance shuttle walking test - Change from baseline in peak performance from incremental shuttle walking test - Change from baseline in COPD Assessment Test (CAT) - Change in PROactive endpoints (individual components and total score) - Change in physical activity measures as assessed via an accelerometer - Patient Global Impression of Change - Patient Global Rating of Severity - Change in St George Respiratory Questionnaire-COPD (SGRQ-c) total score and domains - Change from baseline in forced expiratory volume in 1 second (FEV1) - Change from baseline in Inspiratory capacity (IC) - Change from baseline in Sniff nasal inspiratory pressure (SnIP) - Model specific PK parameters of GSK2881078 (e.g., oral clearance, oral steady-state volume of distribution).;Timepoint(s) of evaluation of this end point: -Throughout the duration of the study | — |
Countries
Germany, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed