A Study of GSK256073 in Subjects With Type 2 Diabetes Mellitus Who Are Being Treated With Metformin
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: GSK256073 1mg; GSK256073 5mg; GSK256073 10mg; GSK256073 25mg; Placebo; Sitagliptin 100mg
Intervention description: GSK256073 1mg capsule; GSK256073 5mg capsule; GSK256073 10mg capsule; GSK256073 25mg capsule; placebo capsule; Sitagliptin 100mg capsule
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 92.0
Sex: All
Minimum age: 20 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Safety; Dose Ranging; Efficacy

Summary:

      The aim of this combined, two part study is to evaluate the safety and glucose lowering
      effects of GSK256073 when administered to diabetic subjects for 12 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A diagnosis of T2DM as determined by a responsible physician based on a medical
             evaluation including medical history, physical examination, and laboratory tests, with
             onset at least 6 months prior to Screening. Subjects may be entered if they have
             stable hypertension or dyslipidemia on therapy. Subjects with other conditions except
             as noted in the Exclusion criteria may be included only if the investigator and GSK
             medical monitor agree that the condition is unlikely to introduce additional risk
             factors and will not interfere with study procedures

          -  HbA1c levels greater than or equal to 7.0 % and less than or equal to 9.5% at
             Screening

          -  On monotherapy with metformin at the time of screening, and at a maximum tolerated
             dose greater than or equal to 1000 mg for at least 2 months prior to dosing.

          -  Fasting plasma glucose level less than 13.3 mmol/L (240 mg/dL) at Screening

          -  Male or female between 20 and 70 years of age, inclusive, at the time of signing the
             informed consent

          -  Fasting Triglycerides lower than 4.52 mmol/L (400 mg/dL)

          -  A female subject is able to participate is she if of non-child bearing potential

          -  Male subjects must agree to use one of the contraception methods listed in the
             protocol. This criterion must be followed from the time of the first dose of study
             medication until 3 days after last dose of the study medication

          -  Overweight with BMI greater than or equal to 25 kg/m2 for non-Asian Indians and
             greater than or equal to 24 kg/m2 for Asian-Indian, and less than 40 kg/m2

          -  The subject is capable of giving written informed consent, which includes compliance
             with the requirements and restrictions listed in the consent form

          -  Subjects in France will be eligible only if they are affiliated to or a beneficiary of
             a social security category

          -  Subjects in other countries must meet all local and/or country-specific requirements
             for registration and reimbursement, as applicable

        Exclusion Criteria:

          -  Requiring insulin therapy or use of combination oral antidiabetic medications or use
             of monotherapy other than metformin within the 3 months prior to screening

          -  Past or present disease (other than type 2 diabetes mellitus) that in the opinion of
             the Investigator may affect the outcome of this study

          -  A positive pre-study Hepatitis B surface antigen, or positive Hepatitis C result
             within 3 months of screening

          -  Renal impairment as defined by a calculated GFR less than 60 mL/min

          -  Any concurrent serious illness (e.g., severe COPD, history of malignancy other than
             skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that
             may interfere with a subject completing the study

          -  Laboratory values as defined per protocol

          -  ECG criteria as defined per protocol

          -  Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater
             than 100 mmHg at Screening

          -  History of uric acid kidney stone, and being treated with drugs for hyperuricemia
             including Allopurinol or Probenecid

          -  History of peptic ulcer disease (PUD) and/or other gastrointestinal bleeding within
             the 12 months prior to screening

          -  Use of certain blood pressure medications or certain other medications that are
             renally excreted as defined per protocol

          -  History of myopathy or CPK value greater than 3 times upper limit of normal at
             screening

          -  The subject has participated in a clinical trial and has received an investigational
             product within 30 days or 5 half-lives or twice the biological effect (whichever is
             longer)

          -  Exposure to more than four new chemical entities within 12 months prior to the first
             dosing day

          -  Any change in diet, exercise habits or smoking status within six weeks prior to
             screening. Any subject that cannot refrain from smoking while in the unit must be
             excluded

          -  History of sensitivity to any of the study medications, including sitagliptin or
             metformin, or components thereof or a history of drug or other allergy that, in the
             opinion of the investigator or GSK Medical Monitor, contraindicates their
             participation

          -  The subject has a positive pre-study drug screen

          -  History of regular alcohol consumption within 6 months of the study as defined per
             protocol

          -  Where participation in the study would result in donation of blood or blood products
             in excess of 500 mL within a 56 day period

          -  Pregnant females as determined by positive serum and/or urine hCG test at screening
             and prior to dosing

          -  Lactating females

          -  Subjects who are unwilling or unable to follow the procedures outlined in the protocol

          -  Subject is mentally or legally incapacitated