Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, pharmacodynamics, safety, pharmacokinetics
Brief summary
This is an escalating dose study in subjects with T2DM, which will consist of four overlapping cohorts receiving 6 days of SB756050 to assess safety, pharmacokinetics, and pharmacodynamics.
Interventions
DRUGSB756050
doses are planned to be 15mg to 600mg doses may be altered based on plasma concentrations
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 18 - 60 years of age, inclusive, at the time of signing the informed consent * A female subject is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory. * Except as noted elsewhere, subjects should have no significant known medical conditions other than T2DM, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECGs. A subject with a clinical abnormality or laboratory parameters that meets
Exclusion criteria
but is outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * BMI (body mass index) within the range 25-35 kg/m2, inclusive. * T2DM diagnosed at least 3 months prior to Screening * Subjects must be treating their T2DM using one of the following regimens: Diet and exercise therapy, Metformin as monotherapy, Sulfonylurea as monotherapy, Metformin and sulfonylurea in combination, DPP-IV inhibitors, either as monotherapy or in combination with other agent(s) on this list at half maximal dose or less, Exenatide, either as monotherapy or in combination with other agent(s) on this list All doses of anti-diabetic medication must have been stable for at least 3 months prior to Screening, and the subject must be willing to wash out from their antidiabetic medications from Day -7 through Day 7. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety measures including: AEs daily; laboratory testing: day -1,2,5,7 and follow up; ECG: day -1, 2, 5, 6, 7 and follow-up; vital signs: daily; PK parameters day -1,5, and 6. | 6 days of dosing |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamic endpoints will include fasting and meal or OGTT-related weighted mean AUC for glucose, GLP-1 (total and active), glucagon, insulin, PYY (active) and C-peptide levels. | 6 days of dosing |
| Safety and tolerability parameters including adverse events, clinical laboratory, ECGs and vital signs assessments. | 6 days of dosing |
| Subject reports of hunger and craving as reported on the Hunger and Craving questionnaire | 6 days of dosing |
Countries
United States
Outcome results
None listed