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Dose-dependent glucosuria of DWP16001, a novel selective SGLT-2 inhibitor, in healthy subjects
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  • Jungi Hwang,
  • SeungHwan Lee,
  • Wan Huh,
  • Jumi Han,
  • Jaeseong Oh,
  • In-Jin Jang,
  • Kyung-Sang Yu
Jungi Hwang
Chungbuk National University Hospital
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SeungHwan Lee
Seoul National University College of Medicine
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Wan Huh
Daewoong Pharmaceutical Co Ltd
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Jumi Han
Daewoong Pharmaceutical Co Ltd
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Jaeseong Oh
Seoul National University College of Medicine
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In-Jin Jang
Seoul National University College of Medicine
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Kyung-Sang Yu
Seoul National University College of Medicine
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Abstract

DWP16001 is a novel sodium-glucose cotransporter-2 (SGLT2) inhibitor under development for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of DWP16001 after single and multiple doses in healthy subjects. A randomized, double-blind, placebo- and active-controlled, single- and multiple-dose study was conducted. Twelve subjects in each dose group received a single dose (0.2, 0.5, 1.0, 2.0, or 5.0 mg) or multiple doses (0.1, 0.3, 0.5, 1.0, or 2.0 mg once daily for 15 consecutive days) of DWP16001, dapagliflozin 10 mg, or placebo, in a ratio of 8:2:2. Serial blood samples and interval urine samples were collected for PK and PD analyses. Safety and tolerability were assessed throughout the study period. A dose-dependent increase in urinary glucose excretion (UGE) was observed after a single dose, and the steady-state UGE was 50–60 g/day after multiple doses in the dose range of 0.3 – 2.0 mg. DWP16001 was rapidly absorbed with the time to peak plasma concentration of 1.0 – 3.0 hours, and eliminated with a mean elimination half-life of 13 - 29 hours. The systemic exposure of DWP16001 increased proportionally with the dose after multiple administrations in the range of 0.1 – 2.0 mg. DWP16001 was well tolerated in all dose groups. DWP16001 caused glucosuria in a dose-dependent manner, and systemic exposure was observed after multiple doses. DWP16001 was well tolerated up to 5.0 mg after a single oral dose and up to 2.0 mg after multiple oral administration

Peer review status:IN REVISION

15 Nov 2021Submitted to British Journal of Clinical Pharmacology
16 Nov 2021Assigned to Editor
16 Nov 2021Submission Checks Completed
27 Nov 2021Reviewer(s) Assigned
12 Dec 2021Review(s) Completed, Editorial Evaluation Pending
01 Jan 2022Editorial Decision: Revise Major