Dose Ranging Study of Albiglutide in Japanese Subjects
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: albiglutide; placebo
Intervention description: subcutaneous injection of albiglutide; subcutaneous injection of placebo to match albiglutide
Intervention MeSH terms: rGLP-1 protein; Glucagon-Like Peptide 1
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 215.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: dose-ranging; pharmacokinetics; GSK716155; Japan; albiglutide

Summary:

      This is a randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose
      ranging study evaluating the dose response, efficacy and safety of subcutaneously injected
      GSK716155 (albiglutide) in Japanese subjects with type 2 diabetes mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject with a historical diagnosis of type 2 diabetes mellitus who is currently
             treated with diet and exercise only or one OAD

          -  BMI ≥18 kg/m2 and <35 kg/m2 at Screening

          -  HbA1c between 7.0% and 10.0%, inclusive

          -  Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)

          -  Female subjects of childbearing potential must be practicing adequate contraception .

          -  Able and willing to monitor his/her own blood glucose concentrations with a home
             glucose monitor.

          -  Able and willing to provide written informed consent

        Exclusion Criteria:

          -  Diagnosis of type 1 diabetes mellitus

          -  Uncorrected thyroid dysfunction

          -  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

          -  Clinically significantly cardiovascular and/or cerebrovascular disease including, but
             not limited to the following:

               -  Previous history of stroke or transient ischemic attack

               -  Active, unstable coronary heart disease within the past six months before
                  Screening

               -  Documented myocardial infarction within one year before Screening

               -  Any cardiac surgery including percutaneous transluminal coronary angioplasty,
                  coronary stent placement, or coronary artery bypass graft surgery within one year
                  before Screening

               -  Unstable angina

               -  Clinically significant arrhythmia or valvular heart disease

               -  Current heart failure NYHA class II to IV

               -  Resting systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg at Screening

               -  ECG criteria at Screening

          -  Heart rate: <40 and >110 bpm

          -  PR interval: <120 and > 210 msec

          -  QRS interval: <70 and >120 msec

          -  QTc interval (Bazett): >450 msec or >480 msec with bundle branch block

          -  Fasting triglyceride level >400 mg/dL at Screening

          -  AST or ALT >2xULN, ALP and bilirubin >1.5xULN (except known Gilbert's syndrome and a
             fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin)

          -  If female, is currently lactating, within 6 weeks post-partum, pregnant, or actively
             trying to become pregnant

          -  Has significant renal disease as manifested by one or more of the following:

               -  Creatinine clearance at screening <60 mL/min (calculated by Cockcroft-Gault
                  formula) at Screening

               -  Known loss of a kidney either by surgical ablation, injury or disease level

          -  A hemoglobinopathy that may affect determination of HbA1c level

          -  History of treated diabetic gastroparesis

          -  History of significant gastrointestinal surgery, including gastric bypass and banding,
             or surgeries thought to significantly affect upper gastrointestinal function

          -  Current ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.

          -  Lipase and amylase at Screening > ULN

          -  Severe diabetic neuropathy, preproliferative retinopathy or proliferative retinopathy,
             history of ketoacidosis or hyperosmolar coma

          -  History of cancer, other than squamous cell or basal cell carcinoma of the skin, that
             has not been in full remission for at least 3 years before Screening. (A history of
             treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II
             is allowed)

          -  Acute or chronic history of liver disease, positive hepatitis B surface antigen
             (HBsAg) or positive hepatitis C testing at Screening

          -  Current and history of alcohol or substance abuse

          -  Clinically significant anaemia or any other abnormal haematological profile that is
             considered by the investigator to be clinically significant

          -  Prior use of a GLP-1 analog

          -  Known allergy to any formulation excipients, or Baker's yeast, or history of drug, or
             other allergy which, in the opinion of the responsible study physician, contradicts
             participation

          -  History of or family history of medullary carcinoma of the thyroid.

          -  History of or family history of multiple endocrine neoplasia type 2

          -  Receipt of any investigational drug within the 12 weeks before Screening