Acute Metabolic Effects of LAF 237 in Type 2 Diabetics

NCT00230464 | Completed Phase 3

• 1 other identifier: CLAF237A2346
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; rate of appearance of glucose; insulin secretion; glucagon

Outcome Measures

Primary Outcomes (1)

• Rate of appearance of endogenous glucose

Secondary Outcomes (6)

• Rate of dissapearance of glucose

• Fasting glucose

• Insulin secretion

• Free fatty acids

• Glucagon

Interventions

LAF 237 DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years with type 2 diabetes, males or females (non-pregnant)
• Time of diagnosis: within 6 months prior to screening, or 1 month prior to screening with no detectable anti-GAD Abs
• Normal physical exam, EKG, blood tests, and urinalysis
• HbA1c=7-11% at screening
• FPG=160-280 mg/dl at screening
• Diabetes controlled by diet and exercise alone or by stable dosage of metformin or sulfonylurea
• BMI=22-45 kg/m2 and with a stable (+/- 2.5 kg) weight for the last 6 months
• Compliant to study requirements \& written consent.

You may not qualify if:

• Pregnant or lactating female
• 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
• Any of the following within the past 6 months: MI, CABG, unstable angina
• ECG abnormalities: second degree AV block (Mobitz 1 and 2), third degree AV block, prolonged QTc (\>450 ms)
• Use of the following medications: class Ia ,Ib, Ic or III antiarrhythmics, insulin, thiazolidinediones, corticosteroids
• Investigational drug treatment within 4 weeks prior to screening unless local health authority guidelines mandate a longer period
• Fasting triglycerides \>700 mg/dl at screening
• Diabetic complications
• Renal disease (creatinine \>1.5 mg/dl-males or \>1.4 mg/dl-female), renal failure, hepatic dysfunction, thyrotoxicosis
• History of gastrointestinal surgery (partial bowel resections, partial gastric resections)
• Donation of one unit of blood within 2 weeks or transfusion within 8 weeks prior to screening

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• Novartis: collaborator

Study Sites (1)

Audie L Murphy VA Hospital

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

1-(((3-hydroxy-1-adamantyl)amino)acetyl)-2-cyanopyrrolidine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ralph A DeFronzo, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 28, 2005
• First Posted: September 30, 2005
• Study Start: November 1, 2004
• Study Completion: September 1, 2005
• Last Updated: January 4, 2006

Record last verified: 2005-09

Locations

US (1)