Solomon S. Steiner, Lutz Heinemann, Roderike Pohl, Frank Flacke, Andreas Pfützner, Patrick V. Simms, Marcus Hompesch. EASD September 18, 2007

Transcription

1 Pharmacokinetics and Pharmacodynamics of Insulin VIAject TM, Insulin Lispro and Regular Human Insulin When Injected Subcutaneously Immediately Before a Meal in Patients with Type 1 Diabetes. Solomon S. Steiner, Lutz Heinemann, Roderike Pohl, Frank Flacke, Andreas Pfützner, Patrick V. Simms, Marcus Hompesch EASD September 18,

2 Technology VIAject TM is a novel composition of regular recombinant human insulin and generally regarded as safe ingredients which cause insulin to: Favor the biologically active monomeric form Prevent reformation of the hexameric state Mask insulin charges, and By so doing speed insulin s absorption from subcutaneous sites 2

3 Presented at the ADA 2006: Phase IIa Study with Patients with Type 1 Diabetes Rapid Absorption of VIAject Compared to Regular Human Insulin 14 Patients Serum Insulin (µu/ml) INS Tmax (min) Mean ± SEM Regular Human Insulin 112 ± 13 VIAject 33 ± 4 p< Time (min) -15 Regular Human Insulin VIAject TM 3

4 Phase 1 Pharmacodynamic Data: Mean Glucose Infusion Rates VIAject v. Humalog & Humulin R 12 GIR mg/kg/min baseline corrected Humulin R 12 IU 10 Humalog 12 IU 8 VIAject 12 IU Time (hours) 4

5 Study Objective Do these improvements in PK/PD parameters translate into improved postprandial metabolic control? 5

6 Phase II Meal Study Patient demographics Sixteen patients (9 male, 7 female) Age 39±10 years BMI 24±2 kg Study design: Cross over with fixed treatment order Patients stabilized by glucose clamp (target BG 120 mg/dl) Glucose turned off prior to meal and insulin dosing Same patient specific dose of Regular Human Insulin (RHI, Humulin R), insulin Lispro (Humalog ) or VIAject was injected s.c. immediately before the meal by means of a syringe in the abdomen Insulin dose 11.7±0.8 IU Standardized meal consisted of 984 kcal, 28 g protein, 140 g carbohydrate and 35 g fat Postprandial glucose excursions were continuously monitored for 8 hours Glucose infusion was re-initiated if BG fell <60 mg/dl 6

7 Phase II Meal Study Pharmacokinetics PK- Parameters RHI Lispro VIAject p-value Early ½ Tmax (min) Ins Tmax (min) Late ½ Tmax (min) 33±4 29±4 13±1 b < a < c = n.s. 139± ±8 34±7 a < b < 0.02 c < ±16 217± ±12 12 b < a < c <

8 Mean Curves Normalized Insulin Concentration Graphs 120 Normalized Insulin Concentrations, 16 patients 100 Percent (%) Time (min) RHI Lispro VIAject 8

9 Individual Curves Improved Postprandial Glycemic Control Patient ADA Limit Blood Glucose (mg/dl) Hyperglycemic Ideal Glycemic Control Hypoglycemic Glucose Infusion Time (hours) RHI Lispro VIAject TM 9

10 Mean Curves Improved Postprandial Glycemic Control Patients Average Blood Glucose 170 RHI 160 Blood Glucose (mg/dl) Meal Lispro VIAject Time (min) 10

11 Mean Curves Improved Postprandial Glycemic Control Patients Average Blood Glucose 160 RHI Blood Glucose (mg/dl) Meal VIAject Lispro Time (min) 11

12 Phase II Meal Study Glucose Infused to Maintain BG Above 60 mg/dl Glucose Infused min (ml) 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 0 Sixteen Patients mean ± SEM 10,461* 4,126 2,284* *RHI vs. VIAject p<0.05, Lispro vs. VIAject / RHI n.s. RHI Lispro VIAject 12

13 Phase II Meal Study Hypoglycemic Risk As Assessed by Glucose Infusion Requirements 30 Sixteen Patients # of patient hours RHI Lispro VIAject VIAject vs. Lispro P<0.05 VIAject vs. RHI P<0.05 RHI vs. Lispro n.s. 13

14 Phase II Meal Study Pharmacodynamics (mg/dl) BG Max - BG Min 91** 84* 69*,** a RHI Lispro VIAject b * RHI vs. VIAject p<0.05, **Lispro vs. VIAject p<0.0001, paired t-test 14

15 Summary VIAject has improved PK/PD properties compared to Lispro and Regular Human Insulin In a meal related study, postprandial glycemic excursions are reduced in patients with Type 1 diabetes after s.c. injection of VIAject in comparison to both Regular Human Insulin and Lispro Reduced risk of late postprandial hypoglycemic events compared to Regular Human Insulin Reduced risk of early and late postprandial hypoglycemic events compared to Lispro 15

16 The End 16