Safety, tolerability, relative bioavailability, pharmacokinetics, and pharmacodynamics of single and multiple doses of the novel oral bofanglutide in healthy Chinese participants.

AIMS: To evaluate the safety, relative bioavailability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral bofanglutide (co-formulated with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate [SNAC]) in healthy Chinese participants.

METHODS

Part A enrolled 44 participants to receive single doses of oral bofanglutide (30, 60, or 90 mg) or subcutaneous bofanglutide injection (0.6 mg). Part B enrolled 48 participants to receive once-daily oral bofanglutide for 14 days (30 mg then 60 mg), with a post-dose fast of 30 or 60 min.

RESULTS

Most treatment-emergent adverse events (AEs) related to oral bofanglutide were grade 1 gastrointestinal AEs; no serious AEs or severe hypoglycemia occurred. In Part A, single-dose relative bioavailability was 0.56% (30/60 mg) and 1.31% (90 mg). The maximum plasma concentration (Cmax) and area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) increased dose‑dependently from 40.95 to 254.47 ng/mL and from 3980.76 to 28180.67 h·ng/mL. In Part B, a 60‑minute post‑dose fast produced approximately twice the exposure of a 30‑minute fast, with apparent relative bioavailability of 9.22% vs. 4.88% (based on repeated-dose exposure with accumulation).

CONCLUSIONS

Oral bofanglutide was safe and well tolerated. The PK/PD profiles support further investigation of once-daily oral bofanglutide for type 2 diabetes and overweight/obesity.