802-P: Safety, Pharmacokinetics, and Pharmacodynamics of Once-Weekly Basal Insulin Fc (BIF) in Japanese Patients with Type 2 Diabetes: A Phase 1 Open-Label, Randomized, Active-Controlled Trial

Abstract

The aim was to investigate the safety, pharmacokinetics (PK) , and pharmacodynamics (PD) of once-weekly Basal Insulin Fc (BIF) , a novel long-acting IgG Fc-fusion protein being developed for the treatment of diabetes. This multiple-site, open-label, randomized, active-controlled, multiple-dose Phase 1 study investigated individualized weekly subcutaneous injections of BIF compared to once-daily insulin degludec over 6 weeks in Japanese patients with T2D on stable doses of basal insulin, with or without antihyperglycemic medication. In a 5-week lead-in period to treatment, all patients titrated insulin degludec to a fasting glucose (FG) target of 100 to 139 mg/dL. Outcomes included safety (primary) and PK and PD (secondary) . ClinicalTrials.gov NCT04276428. Patients were randomized to receive BIF (n=18) or insulin degludec (n=10) . TEAE incidence was low for both BIF (n=4; 22.2%) and insulin degludec (n=2; 20.0%) . All TEAEs were mild, nonserious, and unrelated to BIF. A total of 6 (33.3%) and 2 (20.0%) patients reported hypoglycemic events during BIF and insulin degludec treatment, respectively, none of which were severe. Median tmax was 3 or 4 days. Geometric mean t1/2 of BIF was 15 days. The peak to trough ratio (Cmax to 168 hours postdose concentration after final dose at Week 6) was 1.13. Mean FG was statistically significantly increased from baseline from Weeks 3 to 7 following first dose of insulin degludec but was not increased with BIF (LS means [SE] change: Week 3 BIF, -6.6 [4.7]; degludec, 22.1 [5.9]; Week 7 BIF, -3.5 [7.1]; degludec, 25.3 [9.3] mg/dL) . The 7-point SMPG profile was unchanged with BIF over treatment. In Japanese patients with T2D, once-weekly BIF was well tolerated and associated with prolonged PK and improved glycemic control. PK/PD profiles in Japanese patients are consistent with prior studies and support participation in Phase 3 studies. Disclosure R. Nasu: None. T. Oura: Employee; Eli Lilly Japan K.K. Stock/Shareholder; Eli Lilly and Company. K. Ohwaki: None. M. Imori: Employee; Eli Lilly Japan K.K. K. Furihata: Other Relationship; Eli Lilly and Company, Pfizer Japan Inc. Funding Eli Lilly Japan K.K.