1085-P: Dance 501 Inhaled Human Insulin (INH): Linear Dose Response, Earlier Onset of Action, and Higher Early Effect than s.c. Insulin Lispro (LIS)

Abstract

Dance 501 is a novel liquid formulation of human insulin for inhalation with the Dance 501 inhaler. This randomized, cross-over trial investigated the pharmacodynamic (PD) action and safety of INH in its final formulation vs. LIS during 10-hour glucose clamps in non-smoking subjects with T2D. LIS was injected s.c. at low (12 U), medium (24 U) and high (48 U) doses, INH was inhaled at equivalent doses, assuming a 13% relative biopotency. Twenty-two subjects completed all 6 single dose administrations. INH and LIS demonstrated a linear dose-response relationship and comparable total PD action (AUC_GIR0-10h). Median relative biopotency of INH was 12.3 to 13.0%. PD profiles (Figure) show a more rapid onset of action for equivalent doses of INH vs. LIS (median differences 6.5 to 20 min, p<0.02) and greater action in the first hour after administration (median differences 19.7 to 48.2 mg/kg, p<0.05). No safety issues and no cough were observed with any inhalation. These results nicely confirm and extend to higher doses the results of a previous PK/PD study in type 2 patients with an earlier version of the Dance 501 device and formulation (Zijlstra et al. Diabetes 2015; 64(Suppl 1): A248). In conclusion, Dance 501 showed favorable glucodynamic properties vs. LIS and excellent tolerability and may therefore become a clinically meaningful alternative to rapid-acting insulin injectables. Disclosure E. Zijlstra: Speaker's Bureau; Self; Novo Nordisk A/S. L. Plum-Moerschel: None. M. Ermer: None. O. Klein: None. L. Porter: Other Relationship; Self; Dance Biopharm Holdings Inc., Eiger BioPharmaceuticals. B. Bueche: Employee; Self; Dance Biopharm Holdings Inc. M. Kuo: Employee; Self; Dance Biopharm Holdings Inc. T. Le: None. B.J. Stedman: None. J.S. Patton: Other Relationship; Self; Dance Biopharm Holdings Inc. Funding Dance Biopharm Holdings Inc.