to investigate the safety, tolerability and pharmacodynamics of gsk2890457 in healthy volunteers and subjects with type 2 diabetes

Conditions: Obesity

Summary: this study is the first administration of gsk2890457 in humans. the study will be conducted in 3 parts: - part a (conducted at a single investigative site) will determine the safety and tolerability of gsk2890457 alone in healthy subjects during six weeks of dosing, as well as evaluating the potential for a pharmacokinetic interaction with metformin. part a consists of screening, treatment (6 weeks) and follow-up periods. - part b (conducted at multiple sites) will determine safety, tolerability, and pharmacodynamics (pd) in subjects with type 2 diabetes (t2d) when co-dosed for six weeks with liraglutide (victoza). part b consists of screening, run-in (1 week), stabilization (12 weeks), treatment (6 weeks) and follow-up periods. - part c (conducted at multiple sites) will determine safety, tolerability, and pd in subjects with t2d when co-dosed for 6 weeks with metformin. part c consists of screening, run-in (1 week), stabilization (12 weeks), treatment (6 weeks) and follow-up periods.


Eligibility criteria:
inclusion criteria:part a (healthy subjects) * subject able to understand and voluntarily provide the consent to participate in the study * 18 - 70 years of age, inclusive, at the time of signing the informed consent and body mass index (bmi) between 18.0 and 35.0 kilogram (kg) per m\^2, inclusive * understands and is willing, able and likely to be compliant with taking study drug and comply with all study procedures and restrictions * subject is willing to consume the foods that are part of the standardized breakfast, lunch, and dinner * in good general health with no clinically significant and relevant abnormalities of medical history or physical examination which includes adequate renal function, alanine transaminase (alt), alkaline phosphatase and bilirubin \<=1.5x upper limit of normal (uln ) * qtcf \< 450 millisecond (msec); or qtcf \< 480msec for subjects with right bundle branch block * females must be post-menopausal * females on hormone replacement therapy (hrt) must discontinue hrt to allow confirmation of post-menopausal status prior to study enrollment * females who are \> 3 months postpartum and who have undergone a surgical sterilization procedure are eligible to participate in consultation with the gsk medical monitor parts b and c (type 2 diabetic subjects) * all the criteria mentioned in part a except body mass index (bmi) should be between 30.0 and 42.0 kg per m\^2 * diagnosis of t2d for at least 3 months, as defined by the american diabetes association * all t2d subjects must meet label recommendations for metformin * for part b, subjects must be willing to discontinue metformin and replace it with daily liraglutide administered by subcutaneous injection and they must meet label recommendations * no personal history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 exclusion criteria: * history of gastrointestinal disease, current or chronic history of liver disease, history of serious, severe or unstable physical or psychiatric illness , significant cardiovascular disease, surgery for weight loss or gastrointestinal surgery within 3 months of screening, any documented or reported eating disorder, uncontrolled hypertension, as evidenced by systolic pressure\>160 or diastolic pressure \>90 mmhg * positive test for hiv, hepatitis b, or hepatitis c at screening * subjects with significant ecg abnormalities * for subjects in part c (continuing metformin), history of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia * presence of or symptoms of an active infection * uncorrected thyroid dysfunction * history of chronic or acute pancreatitis * currently dieting to lose weight including, but not limited to, participation in a program designed to alter body weight within the last 60 days and unwilling to maintain relatively consistent exercise patterns throughout the study * current or recent history (within one year of screening) of alcohol or other substance abuse * unable to refrain from the use of non-prescription drugs * current participation in another clinical study or participation in a clinical study involving an investigational drug within 30 days of the screening visit * history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy * an employee of the sponsor or the study site or members of their immediate family.

Keywords: metformin diabetes obesity liraglutide