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Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase.

Publication ,  Journal Article
Darpo, B; Benson, C; Dota, C; Ferber, G; Garnett, C; Green, CL; Jarugula, V; Johannesen, L; Keirns, J; Krudys, K; Liu, J; Ortemann-Renon, C ...
Published in: Clin Pharmacol Ther
April 2015

The QT effects of five "QT-positive" and one negative drug were tested to evaluate whether exposure-response analysis can detect QT effects in a small study with healthy subjects. Each drug was given to nine subjects (six for placebo) in two dose levels; positive drugs were chosen to cause 10 to 12 ms and 15 to 20 ms QTcF prolongation. The slope of the concentration/ΔQTc effect was significantly positive for ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide. For the lower dose, an effect above 10 ms could not be excluded, i.e., the upper bound of the confidence interval for the predicted mean ΔΔQTcF effect was above 10 ms. For the negative drug, levocetirizine, a ΔΔQTcF effect above 10 ms was excluded at 6-fold the therapeutic dose. The study provides evidence that robust QT assessment in early-phase clinical studies can replace the thorough QT study.

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Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2015

Volume

97

Issue

4

Start / End Page

326 / 335

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pharmacology & Pharmacy
  • Male
  • Long QT Syndrome
  • Linear Models
  • Humans
  • Heart Rate
  • Female
  • Electrocardiography
  • Double-Blind Method
 

Citation

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Darpo, B., Benson, C., Dota, C., Ferber, G., Garnett, C., Green, C. L., … Stockbridge, N. (2015). Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase. Clin Pharmacol Ther, 97(4), 326–335. https://doi.org/10.1002/cpt.60
Darpo, B., C. Benson, C. Dota, G. Ferber, C. Garnett, C. L. Green, V. Jarugula, et al. “Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase.Clin Pharmacol Ther 97, no. 4 (April 2015): 326–35. https://doi.org/10.1002/cpt.60.
Darpo B, Benson C, Dota C, Ferber G, Garnett C, Green CL, et al. Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase. Clin Pharmacol Ther. 2015 Apr;97(4):326–35.
Darpo, B., et al. “Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase.Clin Pharmacol Ther, vol. 97, no. 4, Apr. 2015, pp. 326–35. Pubmed, doi:10.1002/cpt.60.
Darpo B, Benson C, Dota C, Ferber G, Garnett C, Green CL, Jarugula V, Johannesen L, Keirns J, Krudys K, Liu J, Ortemann-Renon C, Riley S, Sarapa N, Smith B, Stoltz RR, Zhou M, Stockbridge N. Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase. Clin Pharmacol Ther. 2015 Apr;97(4):326–335.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

April 2015

Volume

97

Issue

4

Start / End Page

326 / 335

Location

United States

Related Subject Headings

  • Prospective Studies
  • Pharmacology & Pharmacy
  • Male
  • Long QT Syndrome
  • Linear Models
  • Humans
  • Heart Rate
  • Female
  • Electrocardiography
  • Double-Blind Method