Evaluation of Continuous Glucose Monitoring as a Tool to Measure Glucoregulatory Effects of a Twice Daily Oral Insulin Secretagogue

In this study the volunteers will participate in an investigation with a
medicine used to treat Type 2 Diabetes Mellitus with the purpose to evaluate a
new method to measure blood glucose (blood sugar) profiles in Type 2 Diabetes
Mellitus patients.
Type 2 diabetes mellitus is a major and still increasing health problem. There
is still a continued unmet need for medications that can lower blood glucose
levels significantly.
In the present clinical practice, fasting blood glucose levels are typically
used to measure blood glucose levels in diabetic patients, sometimes with the
additional determination of several (generally 2 to 4) blood glucose
concentrations over the day.
The above-mentioned measurements are however not capable of capturing the rapid
changes in blood glucose, especially after meals. There are indications that
these changes, for both high and low blood sugar levels, are also important for
the development of late complications of Type 2 Diabetes Mellitus. Therefore,
there exists a need for standardized methods which allow the monitoring of
blood glucose in a more intensive way.
In this study the volunteers will receive vildagliptin (Galvus ®). Vildagliptin
augments the release of insulin from your pancreas in response to a meal.
Galvus ® is a government approved and registered oral drug that lowers blood
glucose levels.

Primary:
To estimate the treatment effects of vildagliptin 50 mg PO BID on 24h
weighted-mean glucose (WMG), using CGM and plasma glucose, collected at the end
of a two-week treatment period.

Secondary:
1) To estimate the treatment effects of vildagliptin 50 mg PO BID on various
glucoregulatory parameters, including but not limited to Hemoglobin A1C and
GLP-1, Glucagon and other incretins.
(2) To evaluate the relationship between circulating levels of incretins and
the various glucoregulatory parameters.
(3) To evaluate the feasibility of CGM as a tool to measure glycemic control,
when compared with more traditional parameters of glycemic control.

This is a fixed sequence, single-blind, placebo-controlled, multi dose study in
a group of ~30 T2DM patients.

Procedures and assessments:
Pre-study and post-study screening and follow-up: clinical laboratory, physical
examination, 12-lead ECG, vital signs, medical history, drug screen, HBsAg,
anti HCV, anti-HIV 1/2; clinical laboratory. Follow-up will be performed by a
phone call.

Observation period: an 8 week washout period, in which all blood glucose
lowering medication other that metformin should be discontinued followed by 4
periods in clinic from Day -1 to Day 4.

Blood sampling:
For blood glucose, insulin and c-peptide, GLP-1, glucagon and PYY samples: On
Day 16 of period 2 and 3, and Day 65 of period 4.
DPP4 samples: On Day 2 Period 1 (Baseline), Day 16 of period 2 and 3 and Day 7,
21, 35 and 65 of period 4

Safety assessments:
Adverse events: throughout the study .
Safety and tolerability: throughout the study .

Pharmacodynamics : plasma and urine glucose concentrations, C-peptide, insulin,
GLP-1/glucagon concentrations.
Pharmacokinetics : Plasma DPP-4i concentrations.
Safety : adverse events, vital signs, ECG-parameters, laboratory parameters,
physical examination.

Procedures: pain, light bleeding, heamatoma, possibly an infection.

Adverse Events Galvus:
The most common side effect with Galvus (seen in between 1 and 10 patients in
100) is dizziness. Common: nausea.
Sometimes: weight loss, loss of appetite, abdominal pain, diarrhea, low blood
sugar, drowsiness.