Diabetes Mellitus, Type 2
Conditions
Keywords
GSK1362885, Pharmacodynamics, Safety, Pharmacokinetics, T2DM, Tolerability
Brief summary
This study is the second administration of GSK1362885 in humans. GSK1362885 is a novel, potent inhibitor of human glycogen phosphorylase (GP) under development for the treatment of type 2 diabetes mellitus (T2DM). This study will investigate the compound's safety, tolerability, pharmacokinetics, and pharmacodynamics in subjects with Type 2 Diabetes Mellitus.
Detailed description
This is the first administration of single doses of GSK1362885 to the target population with T2DM. Based on the mechanism of action which involves reducing hepatic glucose output, it is possible that day time (AM) or night time (PM) dosing of GSK1362885 could produce different plasma glucose lowering effects, acting either on prandial or post-absorptive elevations of HGO. This study is designed to compare glucose profiles following AM and PM doses to determine if there is any advantage to either one. This study will compare glucose profiles following a single dose of GSK1362885 in the morning before breakfast (AM) to a single dose administered at night (PM). These two dosing periods will be randomized and each subject will receive both dosing regimens. A third dosing period (BID) is not randomized, but is included to explore the effects of GSK1362885 on glucose profiles when administered twice daily in a 24 hour timeframe.
Interventions
DRUGGSK1362885
100mg in the AM, 100mg in the PM, 50mg BID
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria apply: * A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests. Subjects may be entered if they have stable hypertension or hyperlipidemia on therapy. Subjects with other conditions except as noted in
Exclusion criteria
may be included only if the Investigator and the GSK medical Monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Male or female between 18 and 65 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/premature ovarian failure defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and estradiol less than 40 pg/ml (\<140 pmol/L) is confirmatory. * BMI within the range 22 to 38 kg/m2 (inclusive). * T2DM diagnosed at least 3 months prior to Screening with: * Fasting plasma glucose (FPG) level less than or equal to 250mg/dL at the Screening visit, * FPG level less than or equal to 270 mg/dL on Day -2 * For subjects taking no antidiabetic medications: HbA1c between 6.5 and 11 percent, inclusive, at Screening visit * For subjects taking one or two antidiabetic medications: HbA1c between 5.8 and 10 percent, inclusive, at Screening visit * 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, if one or both component(s) is being administered at a dose that is less than the maximum dose * DPP-IV inhibitors, either as monotherapy, or in combination with other agent(s) on this list, if one or both component(s) is being administered at a dose that is less than the maximum dose * Exenatide, either as monotherapy or in combination with other agent(s) on this list, if one or both component(s) is being administered at a dose that is less than the maximum dose * All doses of anti-diabetic medication must have been stable for at least 2 months prior to Screening, and the subject must be willing to wash out from their antidiabetic medications from Day -10 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 and tolerability assessments including adverse events and clinical laboratory tests | 7 Days |
| Pharmacodynamics following oral administration (glucose, insulin, c-peptide) | 24 hours |
| Pharmacokinetic parameters: AUC, Cmax, Tmax, t1/2, tlag, Cl/F, and V/F | 24 hours |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacodynamics following BID administration (glucose, insulin, c-peptide) | 24 hours |
| Relationship between pharmacokinetic and pharmacodynamic parameters | 24 hours |
Countries
United States
Outcome results
None listed