open access

Vol 20, No 2 (2013)
Original articles
Published online: 2013-04-05
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Assessment of the cardiac safety and pharmacokinetics of a short course, twice daily dose of orally-administered mifepristone in healthy male subjects

Borje Darpo, Roy Bullingham, Daniel L. Combs, Georg Ferber, Karen Hafez
DOI: 10.5603/CJ.2013.0028
·
Cardiol J 2013;20(2):152-160.

open access

Vol 20, No 2 (2013)
Original articles
Published online: 2013-04-05

Abstract

Background: Mifepristone is approved to control hyperglycemia in adults with endogenous
Cushing’s syndrome and is described as a mildly QTc prolonging drug, based on a TQT study.
The aim of the present study was to assess the effect of mifepristone on the QTc interval at plasma
mifepristone concentrations exceeding those observed in the TQT study.

Methods: Twenty healthy, male volunteers were given three doses of 1200 mg mifepristone
every 12 h with a high-fat meal in a randomized, placebo-controlled 2-period crossover study.
Holter ECG recordings were made on Day 1 and 2.

Results: Eighteen subjects completed the study. Mean peak plasma mifepristone concentrations
were 4.01 μg/mL (CV: 31%) on the fi rst dose and 5.77 μg/mL (CV: 29%) on the third
dose. Mifepristone did not have a meaningful QTc effect. The placebo-corrected, change-from-
-baseline QTcF (ΔΔQTcF) was between –1.6 and 0.7 ms on the fi rst dose (upper bound of 90%
CI 3.8 ms) and the largest ΔΔQTcF on the third dose was 4.9 ms (upper bound of 90% CI: 8.4 ms).
Concentration effect modeling showed a slightly negative slope of –0.01 ms/ng/mL.

Conclusions: Mifepristone did not cause a clinically meaningful QTc prolongation in healthy
volunteers at plasma concent rations of mifepristone and its main metabolites that clearly
exceeded those seen in a previous TQT study.

Abstract

Background: Mifepristone is approved to control hyperglycemia in adults with endogenous
Cushing’s syndrome and is described as a mildly QTc prolonging drug, based on a TQT study.
The aim of the present study was to assess the effect of mifepristone on the QTc interval at plasma
mifepristone concentrations exceeding those observed in the TQT study.

Methods: Twenty healthy, male volunteers were given three doses of 1200 mg mifepristone
every 12 h with a high-fat meal in a randomized, placebo-controlled 2-period crossover study.
Holter ECG recordings were made on Day 1 and 2.

Results: Eighteen subjects completed the study. Mean peak plasma mifepristone concentrations
were 4.01 μg/mL (CV: 31%) on the fi rst dose and 5.77 μg/mL (CV: 29%) on the third
dose. Mifepristone did not have a meaningful QTc effect. The placebo-corrected, change-from-
-baseline QTcF (ΔΔQTcF) was between –1.6 and 0.7 ms on the fi rst dose (upper bound of 90%
CI 3.8 ms) and the largest ΔΔQTcF on the third dose was 4.9 ms (upper bound of 90% CI: 8.4 ms).
Concentration effect modeling showed a slightly negative slope of –0.01 ms/ng/mL.

Conclusions: Mifepristone did not cause a clinically meaningful QTc prolongation in healthy
volunteers at plasma concent rations of mifepristone and its main metabolites that clearly
exceeded those seen in a previous TQT study.
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Keywords

mifepristone, QT/QTc, TQT study, PK, PK/PD, early QT assessment

About this article
Title

Assessment of the cardiac safety and pharmacokinetics of a short course, twice daily dose of orally-administered mifepristone in healthy male subjects

Journal

Cardiology Journal

Issue

Vol 20, No 2 (2013)

Pages

152-160

Published online

2013-04-05

DOI

10.5603/CJ.2013.0028

Bibliographic record

Cardiol J 2013;20(2):152-160.

Keywords

mifepristone
QT/QTc
TQT study
PK
PK/PD
early QT assessment

Authors

Borje Darpo
Roy Bullingham
Daniel L. Combs
Georg Ferber
Karen Hafez

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