The Ultra-rapid Insulin (URI) BioChaperone Lispro (BCLIS) Shows Favorable Pharmacodynamics (PD) and Pharmacokinetics (PK) vs. Faster Aspart (FIA) and Insulin Aspart (ASP) in Insulin Pumps (CSII)
Authors: BODE BRUCE W. , KLEIN OLIVER , SEROUSSI CYRIL , RANSON AYMERIC , ARRUBLA JORGE , CORREIA JOSÉ , GAUDIER MARTIN , SOULA OLIVIER , SOULA RÉMI , ALLUIS BERTRAND , MEIFFREN GRÉGORY , GLEZER STANISLAV , HEISE TIM 
Published: June 2018

This double-blind randomized crossover trial is the first to compare the PD and PK properties of two URIs (BCLIS and FIA) and of a conventional analog (ASP). Forty-three patients with type 1 diabetes received a bolus of 0.15 U/kg of BCLIS, FIA or ASP with CSII on top of a 0.01 U/kg/h basal rate under euglycemic clamp conditions (ClampArt®). Compared to ASP, BCLIS had significantly faster-on and -off PD with higher AUCs in the first two hours, lower AUCGIR 2-6h and earlier tearly0.5GIRmax and tlate0.5GIRmax (Table, Figure). Compared to FIA, BCLIS showed similar early GIR excursions and a significantly faster-off PD with earlier tlate0.5GIRmax. PK was aligned with PD and showed higher early (0-1h) and lower late (2-6h) exposures of BCLIS vs. FIA.Table: Mean±SD PD and PK parametersParameterDefinitionBCLISASPFIAp-valueBCLIS/ASPp-valueBCLIS/FIAAUCGIR 0-2h[mg/kg]PD effect in first two hours592±275500±244566±2760.00380.3127AUCGIR 2-6h[mg/kg]PD effect 2-6 hours post-dose693±329881±387753±2680.00150.3087tearly0.5GIRmax[min]Time to early half-maximum PD44±2257±1942±13&lt;0.00010.9020tlate0.5GIRmax[min]Time to late half-maximum PD210±68232±52228±610.00200.0017AUCINS 0-1h [h.mU/L]Insulin exposure 0-1 hour post-dose68±2743±2259±21&lt;0.00010.0284AUCINS 2-6h [h.mU/L]Insulin exposure 2-6 hours post-dose81±4395±4193±450.00060.0001tlate0.5INSmax[min]Time to late half-maximum insulin concentrations147±48183±68165±59&lt;0.00010.0028

Disclosure
B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. O. Klein: None. C. Seroussi: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. A. Ranson: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. J. Arrubla: None. J. Correia: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. M. Gaudier: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. O. Soula: Board Member; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Employee; Spouse/Partner; ADOCIA. R. Soula: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. Board Member; Self; Cellnovo. B. Alluis: None. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA. S. Glezer: Stock/Shareholder; Self; Sanofi. Stock/Shareholder; Spouse/Partner; Sanofi. Employee; Self; ADOCIA, Novo Nordisk Inc.. Employee; Spouse/Partner; Pfizer Inc., Teva Pharmaceutical Industries Ltd.. Stock/Shareholder; Spouse/Partner; Teva Pharmaceutical Industries Ltd. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi.