154-LB: Accelerating Clinical Development of Janagliflozin, a Novel Antidiabetic Drug, Using Model-Informed Drug Development Strategy

Objectives: To accelerate clinical development of Janagliflozin (JANA), an active inhibitor of sodium-glucose cotransporter 2 (SGLT2), using model-informed drug development (MiDD) strategy.

Methods: Firstly, after receiving the SAD PK and PD (change from baseline in urinary glucose excretion, ∆UGE) profiles in healthy subjects (HS), a PK/PD model was developed and optimized by MAD data in HS. Secondly, we projected PK/∆UGEc/FPG/HbA1c profiles based on HS data using the established quantitative relationship between HS and T2DM patients, where ∆UGEc, FPG corrected ∆UGE, was a novel translational biomarker. Thirdly, the predicted PK/PD profiles were confirmed in a 2-week MAD study in T2DM patients and the dose-HbA1c relationship in T2DM patients after 6-month treatment was predicted.

Results: The predicted PK/PD profiles of JANA in T2DM patients were within 2-fold of the observed data. Prediction performance was showed in Figure 1 and a Phase III trial was allowed after the 2-week MAD study.

Conclusion: This MiDD strategy exhibited a good capability to accelerate early phase clinical development of JANA after confirmation from short-term clinical trials.

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