Phase 1 Study of Safety, Tolerability, PK, and PD of Once-Weekly Basal Insulin Fc (BIF) in Japanese Patients with T2DM

BIF (LY3209590) is a novel, once weekly, long-acting IgG Fc-fusion protein that is being assessed for the treatment of diabetes mellitus. This phase 1, multiple-site, randomized, single-dose, dose-escalation study of BIF included 3 cohorts. Cohorts 1 and 2 each included 12 Japanese insulin-naïve patients with T2DM who were randomized double-blind to receive a single SC dose (dose 1 in cohort 1; dose 2 in cohort 2) of BIF (N=8) or placebo (N=4). Cohort 3 included 7 Japanese patients with T2DM previously treated with basal insulin, with or without a stable dose of up to 2 prespecified types of oral anti-hyperglycemic medications, who received a single SC dose of open-label BIF at dose 3. The primary objective was to investigate safety and tolerability. Secondary objectives included characterization of the PK and PD. ClinicalTrials.gov identifier: NCT03603704. Four patients (12.9%; 1 patient in each treatment group) reported a treatment-emergent adverse event; all were mild and none were related to study drug. Six patients (19.4%) reported hypoglycemic events (most events were with dose 3 and none were severe); each event was self-treatable and resulted in a prompt recovery. PK analyses showed BIF exposure after administration of each dose increased with dose, and tmax was observed by approximately day 4 at all 3 doses. The geometric mean t1/2 estimates ranged from 11 to 16 days across doses. All 3 doses decreased fasting glucose from baseline to day 15. Fasting glucose decreased from day 2 until approximately day 7 or 8 at all doses followed by a trend of fasting glucose returning to baseline. Compared with placebo, BIF at doses 1 and 2 significantly decreased (p<0.1) fasting glucose levels from baseline at most time points between days 3 and 15. In Japanese patients with T2DM, single SC doses of BIF were well tolerated, and the PK and PD of BIF allows weekly dosing. Disclosure K. Ohwaki: Employee; Self; Eli Lilly Japan K. K., Stock/Shareholder; Self; Eli Lilly and Company. K. Furihata: None. R. Nasu: Employee; Self; Eli Lilly Japan K. K. T. Oura: Employee; Self; Eli Lilly Japan K. K., Stock/Shareholder; Self; Eli Lilly and Company. M. Imori: Employee; Self; Eli Lilly Japan K. K. Funding Eli Lilly and Company