Pooled Analysis of Clinical Trials Investigating the Pharmacokinetics (PK) of Ultra-rapid Insulin BioChaperone Lispro (BCLIS) vs. Lispro (LIS) in Subjects with Type 1 (T1D) and Type 2 (T2D) Diabetes

Abstract

BCLIS is an ultra-rapid insulin lispro formulation designed to accelerate the time-action profile vs. conventional short-acting insulin analogs. PK characteristics of single doses of BCLIS and LIS were characterized in four randomized, double-blind, crossover studies in altogether 112 T1D and 51 T2D subjects who received BCLIS and LIS (0.2 U/kg in studies 1 and 2, individualized doses in studies 3 and 4) subcutaneously by syringe. Insulin absorption was consistently faster with BCLIS than with LIS as indicated by reaching early half-maximum insulin levels (early t50%max) 8.4 (95% confidence interval [-9.6;-7.2]) and time to maximum levels (tmax) 10.0 [-14.3;-5.8] min earlier (p<0.0001 for both comparisons). Early insulin exposure was significantly greater for BCLIS for up to 2 hours after administration (Figure). BCLIS also showed faster offset of exposure, with a 22.3 [-28.8;-15.7] min earlier time to late half-maximum insulin levels (late t50%max) (p<0.0001) and a 24% lower late exposure (AUC2-6h; Figure). Total exposure (AUC0-6h) was similar for both formulations in all studies (treatment ratio in pooled analysis 0.99 [0.95;1.03], p=NS). In conclusion, BCLIS consistently shows faster onset and offset of exposure than conventional LIS in both T1D and T2D. Disclosure 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. A. Ranson: 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. B. Alluis: None. E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. 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. G. Meiffren: Employee; Self; ADOCIA. Stock/Shareholder; Self; ADOCIA.