Overview

Acute Metabolic Effects of LAF 237 in Type 2 Diabetics

Status:
Completed

Trial end date:
2005-09-01

Target enrollment:
0

Participant gender:
All

Summary

Incretin hormones (GIP and GLP-1) stimulate insulin release in a glucose dependant manner, hence are necessary for maintenance of normal glucose tolerance. Both GIP and GLP-1 are degraded and inactivated by DPP-4. LAF 237 is an inhibitor of DPP-4 that has been shown to increase meal-stimulated levels of intact GLP-1 in animals and patients with T2DM.. The purpose of the current study is to explore the acute effects of LAF237 on the rate of appearance and disappearance of glucose in type 2 diabetics. Secondary objectives include the effect on FPG, insulin secretion rates, glucagon and FFA levels, and rate of glucose entry from the GI tract.

Phase:

Phase 3

Accepts Healthy Volunteers?

Details

Lead Sponsor:

The University of Texas Health Science Center at San Antonio

Collaborator:

Novartis

Treatments:

Vildagliptin

Criteria

Inclusion Criteria:

1. Age 18-75 years with type 2 diabetes, males or females (non-pregnant)

2. Time of diagnosis: within 6 months prior to screening, or 1 month prior to screening
with no detectable anti-GAD Abs

3. Normal physical exam, EKG, blood tests, and urinalysis

4. HbA1c=7-11% at screening

5. FPG=160-280 mg/dl at screening

6. Diabetes controlled by diet and exercise alone or by stable dosage of metformin or
sulfonylurea

7. BMI=22-45 kg/m2 and with a stable (+/- 2.5 kg) weight for the last 6 months

8. Compliant to study requirements & written consent.

Exclusion Criteria:

1. Pregnant or lactating female

2. History of: type 1 DM, pancreatic injury, secondary diabetes (Cushing, acromegaly),
acute metabolic complications (ketoacidosis or hyperosmolar state) within the past 6
months, torsades des pointes, ventricular tachycardia or ventricular fibrillation

3. Any of the following within the past 6 months: MI, CABG, unstable angina

4. ECG abnormalities: second degree AV block (Mobitz 1 and 2), third degree AV block,
prolonged QTc (>450 ms)

5. Use of the following medications: class Ia ,Ib, Ic or III antiarrhythmics, insulin,
thiazolidinediones, corticosteroids

6. Investigational drug treatment within 4 weeks prior to screening unless local health
authority guidelines mandate a longer period

7. Fasting triglycerides >700 mg/dl at screening

8. Diabetic complications

9. Renal disease (creatinine >1.5 mg/dl-males or >1.4 mg/dl-female), renal failure,
hepatic dysfunction, thyrotoxicosis

10. History of gastrointestinal surgery (partial bowel resections, partial gastric
resections)

11. Donation of one unit of blood within 2 weeks or transfusion within 8 weeks prior to
screening