846-P: Safety and Pharmacokinetics of MBX 1416, a Glucagon-Like Peptide 1 Receptor Antagonist, in Healthy Volunteers—A Phase 1 Randomized Trial

作者：Elisa Fabbrini, Patricia A. Carney, Anastasiya Koshkina, Kristi Schneider, SALOMON AZOULAY · 发表于：Diabetes · 年份：2025 · DOI：10.2337/db25-846-p · 研究领域：Diabetes Treatment and Management

Introduction and Objective: MBX 1416 is a selective, reversible glucagon-like peptide-1 receptor (GLP-1R) antagonist designed to treat post-bariatric hypoglycemia (PBH). We assessed safety, tolerability, and pharmacokinetics (PK) of MBX 1416 in healthy volunteers (HVs). Methods: A double-blind trial (NCT06036784) randomized cohorts 3:1 MBX 1416:placebo (8 HVs/dose level). MBX 1416 was injected subcutaneously in 4 single (SAD; 10-200 mg) or 2 multiple ascending dose (MAD; 10-30 mg weekly) levels. The primary endpoint was safety/tolerability. PK (SAD/MAD) and PD (MAD; glucose and GLP-1 in a mixed meal tolerance test [MMTT]) were assessed. In a third part, single-dose MBX 1416 drug-drug interactions (DDIs) were evaluated vs acetaminophen (to assess gastric emptying [GE]) or rosuvastatin. Results: Overall, 32 (SAD), 23 (MAD), and 14 (DDI) HVs enrolled. MBX 1416 was generally well tolerated (Table). MBX 1416 exposure was dose proportional with median Tmax within 24-48 h and long T1/2 (~90 h) supporting weekly dosing. An apparent increase in GLP-1 peak during MMTT was observed. MBX 1416 resulted in a nonclinically meaningful increase in rosuvastatin Cmax, possibly related to slightly accelerated GE. Conclusion: In HVs, MBX 1416 was generally well tolerated, with PK supporting weekly dosing, PD showing an apparent effect on GLP-1, and minimal DDI with rosuvastatin PK. Disclosure E. Fabbrini: Employee; Janssen Pharmaceuticals, Inc. Stock/Shareholder; Janssen Pharmaceuticals, Inc. Emp...