Hyperinsulinemic Euglycemic Clamp Protocol
The purpose of the study is to determine the safety and efficacy of TRC150094 in male patients with cardiometabolic risk. Cardiometabolic risk which is the overall risk of cardiovascular disease (CVD) and diabetes resulting from the presence of hypertension, HDL cholesterol, insulin resistance, dysglycemia and visceral obesity.
Metabolic Cardiovascular Syndrome
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Phase 2A, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Safety and Efficacy of TRC150094 in Increasing Insulin Sensitivity in Male Patients With Increased Cardiometabolic Risk|
- The safety of TRC150094 once daily dosing for 4 weeks in male patients with increased cardiometabolic risk will be determined. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]Safety parameters will include haematology, safety biochemistry, vital signs, ECG and AE check.
- The efficacy (in increasing insulin sensitivity) of TRC150094 once daily dosing for 4 weeks in male patients with increased cardiometabolic risk will be determined. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Efficacy assessment will include Insulin Sensitivity to be determined by:
Rate of Glucose Disposal Suppression of Endogenous Glucose Production Suppression of rate of lipolysis
- The effect of TRC150094 on hepatic fat and metabolic parameters will be evaluated. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
Early efficacy markers to be explored includes:
- Hepatic fat by magnetic resonance spectroscopy
- Lipid parameters
- Metabolic markers such as adiponectin, IL-6, TNF-alpha, CRP, glucagon, leptin etc.
- The ethnic differences for effect of TRC150094 on Insulin sensitivity parameters will be evaluated. [ Time Frame: 1 month ] [ Designated as safety issue: No ]Difference in insulin sensitivity parameters (rate of glucose disposal) between caucasian and Indian populations.
|Study Start Date:||November 2011|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
Tablets once daily
|Active Comparator: TRC150094||
50 mg Tablets once a day
20 Subjects will be enrolled in Veeda Clinical research,India and another 20 subjects at Amsterdam, the Netherlands. The maximum duration of participation in the study for each subject will be 9.5 weeks including a less than or equal to 4 weeks screening period, 4 weeks of treatment and a 10 days post treatment follow-up evaluation period.
At each study site, 20 subjects will be enrolled. Each subject will attend the study centre in a fasting state, for a screening visit, 2 study visits (one baseline and one end of treatment), 1 intermediate safety visit and 1 post-study follow-up visit (Total 5 visits). The subjects at each site will be randomized to receive TRC150094 or placebo in a ratio of 1:1. 50 mg dose will be administered once daily (morning) under fasting conditions. Dosing will take place daily on Days 1-28. Subjects will arrive at the study centre for screening visit. Physical examination, vital signs, safety biochemistry and laboratory investigations for verification of inclusion/ exclusion criteria will be performed during screening visit. Subjects meeting all the inclusion criteria and none of the exclusion criteria and who have given their informed consent for the study will be asked to come for the study on Day 0 (or day -1 if required). Baseline investigations (including baseline clamp procedure and hepatic MRS) will be done on Day 0 (or day -1). Subjects will receive properly labelled bottle containing either Active treatment or Placebo as per the randomization number of the subject.
|Academic Medical Centre,|
|Amsterdam, Netherlands, 1100 DD|
|Principal Investigator:||Erik Stroes, MD, PhD||Department of Vascular Medicine, AMC|