Development of a Steady-State Exposure-Response Model for Exenatide Once Weekly

Authors: Cirincione B, Passarell JA, Kothare PA, Cummings M, Grasela TH, Fineman MS
Conference: ASCPT
Keywords: antidiabetic agents, body mass index, CrCL, Endocrinology, exendin, glycated hemoglobin, hemoglobin A1c, hormones, ideal body weight, metformin, pharmacodynamic, pharmacokinetic, PK/PD, QW, renal function, subcutaneous, sulfonylurea, thiazolidinedione
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Exenatide is dosed as a subcutaneous (SC) injection of 5 and 10 μg twice daily (BID) before main meals and is indicated for the treatment of type 2 diabetes mellitus in patients failing to achieve adequate glycemic control with metformin (MET), a sulfonylurea (SFU), a thiazolidinedione (TZD), a combination of MET and a SFU, or a combination of MET and a TZD
  • Model-based assessments were extensively used to support dose selection in the exenatide clinical development program
  • Exenatide once weekly (QW) is being developed as a line extension of exenatide BID administered SC once a week to subjects with type 2 diabetes mellitus
  • These analyses describe the empirical relationship between exenatide exposure and glycemic response and constitute an integral part of the dose justification assessment of exenatide 2 mg QW

American Society for Clinical Pharmacology and Therapeutics (ASCPT), National Harbor, Maryland, March 2009

By B Cirincione, Julie Passarell, P Kothare, M Cummings, Thaddeus H. Grasela, M Fineman