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Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study.

Publication ,  Journal Article
Jung, SY; Hwang, S; Clarke, JM; Bauer, TM; Keedy, VL; Lee, H; Park, N; Kim, S-J; Lee, JI
Published in: Invest New Drugs
June 2020

Purposes Vactosertib is a new investigational inhibitor of activin receptor-like kinase 5. The objective of this study was to characterize vactosertib pharmacokinetics that are to be applied for subsequent clinical studies. Methods Vactosertib plasma concentration-time data were obtained from a multicenter, dose-escalation, first-in-human phase 1 study conducted in patients with advanced solid tumors. Each patient orally received a fixed dose of vactosertib with the range of 30 mg to 340 mg once daily under fasted condition. Pharmacokinetic analysis was performed using a non-compartmental method. Results Pharmacokinetic data were evaluable in 29 patients. Vactosertib was rapidly absorbed after the first dose with a median time to maximum concentration (tmax) of 1.2 h (interquartile range, 0.8-1.8 h) and quickly eliminated with a median terminal half-life (t1/2) of 3.2 h (2.2-4.2 h) over the dose range studied. Such trend was also observed after repeated doses for five days (median tmax, 1.5 h; median t1/2, 3.0 h). The area under the concentration-time curve within a dosing interval increased in proportion to dose. The median values of apparent clearance and volume of distribution were 29 L/h (21-44 L/h) and 133 L (77-222 L), respectively. The median accumulation ratio after repeated once-daily doses for five days was 0.87 (0.69-1.07). Conclusions Vactosertib pharmacokinetics were dose-proportional within tested dose range with negligible accumulation when administered once daily for five days. Considering the short half-life, it seems necessary to administer vactosertib twice- or thrice-daily to maintain its concentrations above minimum effective level over a dosing interval.

Duke Scholars

Published In

Invest New Drugs

DOI

EISSN

1573-0646

Publication Date

June 2020

Volume

38

Issue

3

Start / End Page

812 / 820

Location

United States

Related Subject Headings

  • Triazoles
  • Receptor, Transforming Growth Factor-beta Type I
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Humans
  • Half-Life
  • Female
  • Drug Administration Schedule
 

Citation

APA
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Jung, S. Y., Hwang, S., Clarke, J. M., Bauer, T. M., Keedy, V. L., Lee, H., … Lee, J. I. (2020). Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study. Invest New Drugs, 38(3), 812–820. https://doi.org/10.1007/s10637-019-00835-y
Jung, Su Young, Sunjin Hwang, Jeffery M. Clarke, Todd M. Bauer, Vicki L. Keedy, Hukeun Lee, Neunggyu Park, Seong-Jin Kim, and Jangik I. Lee. “Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study.Invest New Drugs 38, no. 3 (June 2020): 812–20. https://doi.org/10.1007/s10637-019-00835-y.
Jung, Su Young, et al. “Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study.Invest New Drugs, vol. 38, no. 3, June 2020, pp. 812–20. Pubmed, doi:10.1007/s10637-019-00835-y.
Jung SY, Hwang S, Clarke JM, Bauer TM, Keedy VL, Lee H, Park N, Kim S-J, Lee JI. Pharmacokinetic characteristics of vactosertib, a new activin receptor-like kinase 5 inhibitor, in patients with advanced solid tumors in a first-in-human phase 1 study. Invest New Drugs. 2020 Jun;38(3):812–820.
Journal cover image

Published In

Invest New Drugs

DOI

EISSN

1573-0646

Publication Date

June 2020

Volume

38

Issue

3

Start / End Page

812 / 820

Location

United States

Related Subject Headings

  • Triazoles
  • Receptor, Transforming Growth Factor-beta Type I
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Humans
  • Half-Life
  • Female
  • Drug Administration Schedule