Effects of KDT501 on Metabolic Features in Insulin Resistant Subjects

Inclusion criteria

• Written informed consent obtained prior to the initiation of study procedures
• Age is 40-70 years
• Diagnosis IGT, IFG, or metabolic syndrome

• IGT is defined as: a) 2 hour OGTT glucose 140-199mg/dL and b) fasting glucose <126 mg/dL
• IFG is defined as: a) 2 hour OGTT glucose < 200 mg/dL and b) fasting glucose 100-125 mg/dL
• Metabolic syndrome is defined as meeting at least 3 of the following criteria: a) serum triglycerides >150 mg/dL; b) serum HDL<40 mg/dl (males) or <50 (females); c) BP>130/85 or on medical treatment; d) waist circumference >40" (males) or >35" (females); e)HbA1c>5.7%
• Prior therapy for IGT and IFG may include diet alone
• HbA1c <7.0% within 28 days of registration
• Fasting plasma glucose <126 mg/dL within 28 days of registration
• Body mass index (BMI) ≥27 kg/m2
• Women of child-bearing potential have a negative serum pregnancy test result ≤28 days prior to registration and agree not to breastfeed during investigational treatment with KDT501 and for 28 days following the final dose of KDT501.
• All males and premenopausal females who have not been surgically sterilized have agreed to practice a method of birth control considered by the Investigator to be effective and medically acceptable for at least 14 days prior to registration, throughout treatment, and for 28 days following the final dose of KDT501.
• Adequate baseline hematologic, renal, and liver function as evidenced by laboratory test results within the following ranges (obtained ≤28 days prior to registration):

• Hemoglobin >11.0 gm/dL
• Platelet Count ≥100 x 10^3/μL
• White Blood Count ≥2.0 x 103/μL and ≤15.0 x 103/μL
• Creatinine Clearance ≥60 mL/min
• Total Bilirubin ≤2 x upper limit of normal (ULN)
• Aspartate Transferase (AST) ≤2.5 x ULN
• Alanine Transferase (ALT) ≤2.5 x ULN
• INR< 1.5 and PTT <1.5 ULN
• World Health Organization (WHO) performance status 0-1

Exclusion criteria

• Prior or current history of T2DM
• Type 1 diabetes
• Subjects with IGT or IFG who have hypoglycemic unawareness and/or recurrent severe hypoglycemia
• NYHA CHF Class 2-4
• Any significant, active pulmonary disorder including FEV1 <60% predicted based on outpatient spirometry
• History of any significant cardiovascular disease, including arrhythmia, clinically significant ECG abnormality, uncontrolled hypertension, myocardial infarction or unstable angina pectoris within the past 6 months
• History of HIV or AIDS
• Active Hepatitis B or C infection requiring therapy within the past 6 months
• History of any significant, active gastrointestinal disorder, including GERD>grade 2 severity
• History of gastrectomy or any other GI tract surgery that may affect digestion or absorption
• Positive fecal occult blood
• Concomitant therapy with anticoagulants, aspirin or aspirin containing products. Low dose aspirin (≤81 mg qd) is allowed if PT/INR and aPTT values are WNL.
• Any significant, active hematological disorder
• Concomitant therapy with CYP2C9 substrates or inhibitors
• Any major surgery (e.g., surgery requiring general anesthesia) ≤28 days prior to registration
• Systemic treatment on any investigational clinical trial ≤28 days prior to registration
• Systemic glucocorticoid or immunosuppressive therapy use ≤28 days prior to registration. Use of a short course (i.e., ≤1 day) of a glucocorticoid is acceptable to prevent a reaction to IV contrast used for CT scans. Topical and inhaled steroid medications are allowed.
• Any infection requiring parenteral antibiotic therapy or causing fever (i.e., temperature >100.5°F or >38.1°C) ≤7 days prior to registration
• A contraindication to the use of KDT501
• Any medical intervention, has any other condition, or has any other circumstance which, in the opinion of the Investigator or the KinDex Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives