501 inhaled insulin (INH) is a novel liquid formulation of human insulin for inhalation with faster onset of action than s.c. insulin lispro (LIS). This randomized, replicated cross-over trial investigated the variability of INH vs. LIS during 10-hour glucose clamps in non-smoking subjects with T1D. Fourteen subjects (age [mean±SD] 32.5±7.9 years, BMI 26.5±2.1 kg/m2, HbA1c 7.5±0.8 %) received 2 single doses of 92.2 IU INH via the Afina inhaler (n=13 completing subjects) and 2 injections of an equivalent 12 U LIS dose (n=12). The inhalations were performed by the subjects after a brief training on the correct inhalation technique; injections were given by trained staff. Repeated dosing of INH by the same subject resulted in reproducible insulin absorption and insulin action, with lower or similar variability vs. LIS (Table 1). The response to INH between subjects was more variable than for LIS. The 13.8±8.1% mean relative biopotency of INH was consistent with previous findings. INH was well tolerated, adverse events (8 with INH, 13 with LIS) were mild to moderate in severity. No cough and no acute changes in spirometry were observed with any inhalation.
In conclusion, the intra-individual response to self-administration of 501 inhaled insulin is as reproducible as that of s.c. insulin lispro injected by experienced staff. This is a clinically meaningful outcome and enables individual dose titration of 501 insulin in future treatment.
E. Zijlstra: Employee; Self; Profil. Speaker’s Bureau; Self; Aerami Therapeutics, Eli Lilly and Company, Novo Nordisk A/S. G. Andersen: Employee; Self; Profil Institute for Clinical Research. L. Plum-Moerschel: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S. M. Rhodes: None. R. Patton: None. B. Bueche: None. M. Kuo: None. T.H. Le: None. B.J. Stedman: None. J.S. Patton: Board Member; Self; Dance Biopharm Holdings, Inc.