Out-Patient Study in Patients With Type 2 Diabetes Mellitus Who Are Taking no Diabetes Medication or Metformin Only

A 16-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of Multiple Doses and Multiple Treatment Regimens of GSK716155, With Byetta as an Open Label Active Reference, in Subjects With Type 2 Diabetes Mellitus

This study is a placebo-controlled study in patients with Type 2 Diabetes Mellitus who are either taking no diabetes medication or who are taking metformin only. This study will investigate the safety, tolerability, and efficacy of Albiglutide (GSK716155) and will measure the levels of Albiglutide (GSK716155) in the bloodstream when it is given for 16 weeks. As a comparison, some subjects will receive exenatide instead of Albiglutide (GSK716155). The study will involve weekly visits for 17 weeks,and less frequent follow-up visits for an additional 10 weeks. Assessments include repeat blood sampling and monitoring of any side effects.

A 16-week, parallel-group, double-blind, randomized, placebo-controlled, multicenter, dose-ranging study to evaluate the efficacy, safety and tolerability of multiple doses and multiple treatment regimens of Albiglutide (GSK716155) with Byetta as an open-label active reference, in subjects with Type 2 Diabetes Mellitus.

Inclusion Criteria:

• Has type 2 diabetes mellitus as defined by the criteria of the American Diabetes Association and recognized by World Health Organization Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [American Diabetes Association, 2004a] at least three months preceding screening
• Has concurrent type 2 diabetes mellitus therapy: Must be diet and exercise treated; must not have taken antidiabetic medication for at least three months prior to prescreening or Monotherapy with metformin, with a history of a stable dose for at least three months before prescreening (not taking more than one oral antidiabetic agent)
• Has HbA1c level at screening ≥7 and ≤10%
• Is male or female 18 to 75 years of age, inclusive, at screening
• Has body mass index ≥20 and ≤40 kg/m²
• If subject is a smoker, must be able to abstain while in clinic at each visit
• If female, is eligible to enter and participate throughout the study, including the follow-up period: 1) If of nonchildbearing potential (i.e. physiologically incapable of becoming pregnant {tubal ligation}, including any female who is postmenopausal [>1 year without menstrual period]); or, 2) If of childbearing potential, has negative pregnancy tests at screening (serum) and at baseline (urine) and: 3) Has a male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or 4) Uses double-barrier methods of contraception; condoms (with spermicide) and intrauterine devices are acceptable, or 5) Uses hormonal contraceptives (oral, depots, patches, etc) with double-barrier methods of contraception as outlined above, or, 6) Abstains from sexual intercourse, or 7) Is with a same-sex partner and does not participate in bisexual activities where there is any risk of pregnancy
• Signs and dates informed consent before any study-related procedures are performed

Exclusion Criteria:

• Has metabolic disease including but not limited to: 1) Diagnosis of type 1 diabetes mellitus, 2) Uncorrected thyroid dysfunction (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least three months prior to screening, and who have a screening thyroid-stimulating hormone within the limits of normal may participate)
• Has qualitative changes in lifestyle that, in the opinion of the investigator, would affect the subject's weight or disease status
• Had previous use of insulin within one month prior to screening, or more than seven total days of insulin treatment within three months prior to screening
• Has clinically significant cardiovascular and/or cerebrovascular disease including, but not limited to: 1) Previous history of stroke or transient ischemic attack, 2) Active, unstable coronary heart disease within the past six months, 3) Documented myocardial infarction within a year prior to screening 4) Any cardiac surgery including percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery within a year prior to screening 5) Unstable angina 6) Clinically significant arrhythmia or valvular heart disease within the past year 7) Congestive heart failure with New York Heart Association Class II to Class IV symptoms. Class I is acceptable. 8) Untreated hypertension, with systolic pressure greater than 160mm Hg and/or diastolic pressure greater than 95mm Hg. 9) ECG exclusion criteria: Heart rate is <40 and >110 beats per minute, PR Interval is <120 and >210msec, QRS duration is <70 and >120msec, QTc interval (Bazett) is >450msec or >480msec with bundle branch block
• Has fasting serum triglycerides ≥800mg/dL or 9mmol/L at screening (Visit 2). Subjects receiving lipid-lowering therapy must have been on the same dose of therapy for the past three months. Fasting is defined as no food/drink for at least eight hours prior to sampling
• If female, is currently lactating, pregnant, or actively trying to become pregnant
• Has significant renal disease as manifested by one or more of the following: 1) Creatinine clearance <60mL/min. (estimated from serum creatinine and demographic data using the modification of diet in renal disease calculation; refer to the SPM/ISFM), 2) Urine albumin excretion ≥500 µg/mL on a urine spot check, 3) Known loss of a kidney either by surgical ablation, injury, or disease
• Has history of significant comorbid diseases active within the last six months (e.g., gastrointestinal disease)
• Has history of pancreatitis within five years prior to randomization
• Has a documented history of chronic or advanced hepatobiliary disease including a history of, or positive laboratory results for, hepatitis at screening (Visit 2), and/or clinically significant hepatic enzyme elevation including: 1) Any two of the following enzymes greater than 1.5 times the upper limit of normal (ULN) value: - alanine aminotransferase (ALT), - aspartate aminotransferase (AST), - alkaline phosphatase (ALP), 2) Any one of the above enzymes two times greater than the ULN value AND total or direct bilirubin >1.5 times the ULN
• Has a history of alcohol or substance abuse within the past year, as determined by the investigator or a positive urine drug screen at screening (Visit 2) or during treatment: 1) Unwilling to refrain from the use of excessive alcohol or illicit drugs and adhere to other protocol-stated restrictions while participating in the study, 2) History of alcohol abuse defined as an average weekly intake of greater than 21 units or an average daily intake of greater than three units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than two units (females). One unit is equivalent to a half-pint of beer or one measure of spirits or one glass of wine, 2) The investigator should exercise their medical judgment to determine if a urine drug screen is indicated
• Is currently taking prohibited concomitant medications listed in Section 6.6.2
• Has clinically significant anemia (i.e., hemoglobin <12.0g/dL or <120.0g/L for males and <11.0g/dL or <110.0g/L for females) or any other abnormal hematological profile that is considered by the investigator to be clinically significant
• Has known allergy to any formulation excipients, or history of drug or other allergy, which, in the opinion of the responsible study physician, contradicts participation
• Received treatment with an investigational drug or participated in any other clinical trial during the previous 30 days
• Has prior use of investigational agents with long half-lives of greater than seven days within the three months prior to screening
• Has any prior use of a GLP-1 analog, including GSK716155
• In the opinion of the investigator, has a risk of noncompliance with study procedures, or cannot read, understand, or complete study-related materials, particularly the informed consent
• Has any concurrent condition or any clinically significant abnormality identified on the screening physical examination, laboratory tests, ECG, including pulmonary, neurological, or inflammatory diseases, which, in the opinion of the investigator, may affect the interpretation of efficacy and safety data, or which otherwise, contraindicates participation in a clinical trial with a new chemical entity