Clinical trial NCT00651105: Effect of LAF237 on Glucagon Secretion in Patients With Type 2 Diabetes and in Healthy Subjects
Official title: A Double-blind, Placebo-controlled, Randomized, Cross-over Study to Evaluate the GLP-1-mediated and Non-GLP-1-mediated Effects of LAF237 on Glucagon Secretion in Patients With Type 2 Diabetes and in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type-2 Diabetes
Healthy
Keywords: Diabetes
Hyperglycemia
Healthy
Vildagliptin
Adults
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-04-02
Enrollment: 63
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the GLP-1 and non-GLP-1 effects of LAF237 on glucagon secretion, using treatment observations of the overall glycemic response.


Eligibility criteria: Inclusion Criteria:

Inclusion criteria - Type-2 Diabetes Patients

* Male or female patients aged 30 to 75 years with Type-2 Diabetes Mellitus (T2DM) and who are in otherwise good health
* Must have been diagnosed with T2DM at least 6 months prior to screening, and whose diabetes is controlled by diet and exercise alone or by stable dosage ( \> 3 months) of metformin
* HbA1c in the range of 6.5% to 9% at screening

Inclusion Criteria - Healthy Volunteers

* Male or female subjects aged 30 to 75 years, determined to be in good health
* Normal oral glucose tolerance test (OGTT) at screening
* Age, gender and weight matched to subjects with T2DM

Exclusion Criteria:

Exclusion criteria - Type-2 Diabetes Patients

* A history of:
* Type 1 diabetes, diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly
* Acute metabolic diabetic complications (such as ketoacidosis or hyperosmolar state (coma)) within the past 6 months
* Torsades de Pointes, ventricular tachycardia or ventricular fibrillation
* Any severe hypoglycemic episode within 3 months of screening
* Use of any of the following medications:
* Antihypertensive or lipid-lowering agents unless on a stable dose for at least 3 months prior to screening
* Chronic insulin treatment (\> 4 weeks of treatment in the absence of an intercurrent illness) within the past 6 months
* Chronic oral/intramuscular/intravenous corticosteroid treatment ( \> 7 consecutive days of treatment) within 8 weeks prior to screening

Exclusion Criteria - Healthy Volunteers

* First degree relative of an individual with T2DM
* History of gestational diabetes
* Use of any prescription medication within 1 month prior to dosing. Use of over-the-counter medications or vitamins within 14 days prior to dosing.

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: GLP-1 and non GLP-1 effects of LAF237 on glucagon secretion in patients with Type-2 diabetes and matching healthy subjects
timeFrame: from baseline to Day 10
Secondary outcomes:
measure: Effects of LAF237 on prandial glucose profiles, prandial insulin, and gastric-emptying in patients with Type-2 diabetes and in matching healthy subjects.
timeFrame: 10 day treatment periods
Other outcomes:
Locations:
city: Bad Lauterberg im Harz
country: Germany
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nauck MA, Kind J, Kothe LD, Holst JJ, Deacon CF, Broschag M, He YL, Kjems L, Foley J. Quantification of the Contribution of GLP-1 to Mediating Insulinotropic Effects of DPP-4 Inhibition With Vildagliptin in Healthy Subjects and Patients With Type 2 Diabetes Using Exendin [9-39] as a GLP-1 Receptor Antagonist. Diabetes. 2016 Aug;65(8):2440-7. doi: 10.2337/db16-0107. Epub 2016 Apr 5.