A PHASE II, RANDOMIZED, CROSS-OVER, DOUBLE-BLIND, PLACEBO-CONTROLLED, SINGLE CENTER STUDY OF THE EFFECT OF EMPAGLIFLOZIN, A SGLT-2 INHIBITOR, ON ENDOGENOUS GLUCOSE PRODUCTION AND PLASMA GLUCAGON LEVELS IN PATIENTS WITH END-STAGE RENAL DISEASE (ESRD)

INTERVENTION: Trade Name: JARDIANCE ‐ 25 MG ‐ COMPRESSA RIVESTITA CON FILM ‐ USO ORALE ‐ BLISTER (PVC/ALU) ‐ 28 COMPRESSE Product Name: JARDIANCE Product Code: JARDIANCE Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: EMPAGLIFLOZIN CAS Number: 864070‐44‐0 Current Sponsor code: EMPAGLIFLOZIN Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Patients with end‐stage renal disease (ESRD) with or without Type 2 diabetes ; MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 ‐ Metabolism and nutrition disorders ; MedDRA version: 21.1 Level: LLT Classification code 10014647 Term: End stage renal failure System Organ Class: 100000004857 Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: To test the hypothesis that a single empagliflozin (25 mg) oral administration in subjects with ESRD (end‐stage renal disease) will stimulate EGP (Endogenous Glucose Production) and increase plasma glucagon concentration as compared to placebo Primary end point(s): The primary endpoint is the mean difference in EGP and plasma glucagon concentration during the last hour of EGP measurement between empagliflozin versus placebo administration in patients with end‐stage renal disease Secondary Objective: To test the hypothesis that a single empagliflozin (25 mg) oral administration in subjects with ESRD (end‐stage renal disease) will modulate plasma glucose, insulin, c‐peptide, FFA, GH, epinephrine, norepinephrine, cortisol and blood pressure as compared to placebo Timepoint(s) of evaluation of this end point: This timepoint will be achieved in a three‐year study; ; SECONDARY OUTCOME: Secondary end point(s): The secondary endpoints are the mean difference in plasma glucose, insulin, c‐peptide, FFA, GH, epinephrine, norepinephrine, cortisol and blood pressure during the last hour of the experiment between empagliflozin versus placebo administration in patients with end‐stage renal disease Timepoint(s) of evaluation of this end point: This timepoint will be achieved in a three‐year study; ; INCLUSION CRITERIA: 1. Males and females 2. Age = 30‐70 years 3. BMI< 40 Kg/m2 and stable weight (± 3 lbs) over the preceding three months 4. Normal Glucose Tolerance (HbA1c > 4.5 % and < 5.7%) or Type 2 diabetes (HbA1c > 5.7 % and <10.0%) 5. End Stage Renal Disease (GFR <15 ml/min/1.73 m2 or hemodialysis) 6. Subjects are capable of giving informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15