Type 2 Diabetes Mellitus MedDRA version: 14.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: GSK1070806
Pharmaceutical Form: Solution for infusion
Current Sponsor code: GSK1070806
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply. 1. 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, provided there is no change in either the type or dose of medications during the 3-month period before the study. 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. 2. Male or female between 18 and 70 years of age inclusive, at the time of signing the informed consent. 3. HbA1c levels = 7.0 % and = 9.5%; at Screening. 4. On a stable dose of monotherapy with metformin for three months prior to screening, and at a total daily dose greater than or equal to 1000 mg for at least 2 months prior to dosing. 5. Fasting plasma glucose level 40 MlU/ml and estradiol 1.5xULN
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Current evidence, or history within the last 7 days, of an influenza-like illness as defined by fever (>38°C) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea in the absence of a known cause, other than influenza. 2. Use of anti-inflammatory drugs including corticosteroids, chronic maintenance therapy with NSAIDs, anti-Tumor Necrosis Factor (anti-TNF) or anti-Interleukin-1 (anti-IL1) within 60 days prior to dosing. NSAIDs are permitted for intermittent use during the course of the study. 3. Current evidence of ongoing or acute infection, history of repeated, chronic or opportunistic infections (e.g. recurrent folliculitis, other cutaneous infections or repeated pneumonia) or history of a serious bacterial infection within 6 months of randomisation. 4. History of malignancy or significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial. 5. History chronic granulomatous infections, such as of Mycobacterium tuberculosis or any other previous Mycobacterium infection. 6. Creatinine clearance less than 60ml/min 7. Screens positive of Hepatitis B surface antigen, Hepatitis C antibody or Human Immunodeficiency Virus (HIV) 8. History of a severe allergic reaction, anaphylaxis or immunodeficiency. 9. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 10. A positive pre-study drug/alcohol screen. 11. History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. 12. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 13. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 14. Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 15. History of sensitivity to any of the study medications, 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. 16. Where participation in the stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of two repeat intravenous dose administrations of GSK1070806 in subjects with T2DM.; Secondary Objective: • To evaluate the safety and tolerability of two repeat intravenous dose administrations of GSK1070806 in obese subjects with T2DM. • To evaluate the effect of two repeat intravenous dose administrations of GSK1070806 on additional markers of efficacy, in obese subjects with T2DM. • To evaluate the plasma PK of repeat intravenous doses of GSK1070806 in obese subjects with T2DM. • To investigate the effect of repeat intravenous doses of GSK1070806 on free and drug bound IL 18 levels (if measurable) in obese subjects with T2DM. • To explore the pharmacodynamic (PD) effect of repeat intravenous doses of GSK1070806 on biomarkers of inflammation and metabolic disease. • To investigate the effect of repeat intravenous doses of GSK1070806 on body composition in obese subjects with T2DM. Secondary Objectives • To assess the potential of anti-GSK1070806 antibody formation following repeat intravenous administration of GSK1070806. ;Primary end point(s): Change from baseline in fasting plasma glucose and weighted mean glucose AUC (0-4hrs) post-Mixed Meal Test (MMT);Timepoint(s) of evaluation of this end point: Days 29, 57 and 85. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Days 29, 57 and 85.; Secondary end point(s): • Safety and tolerability parameters include: adverse events , clinical laboratory tests, electrocardiograms (ECGs), and vital signs. • Change from baseline in % HbA1c, fasting blood insulin, and C-peptide levels • Change from baseline in weighted mean insulin and C-peptide levels [AUC (0-4hrs)] post-MMTand derived measures of insulin sensitivity and ß-cell function. | — |
Countries
Spain, United Kingdom
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline
Outcome results
None listed