A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity. / Taubel, Jorg; Mazzetti, Alessandro; Ferber, Georg; Burch, William; Fernandes, Sara; Patel, Avani; Spencer, Christopher S.; Freier, Anne; Graff, Claus; Kanters, Jorgen K.; Camm, John.

In: Clinical Pharmacology in Drug Development, Vol. 10, No. 6, 2021, p. 572-581.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Taubel, J, Mazzetti, A, Ferber, G, Burch, W, Fernandes, S, Patel, A, Spencer, CS, Freier, A, Graff, C, Kanters, JK & Camm, J 2021, 'A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity', Clinical Pharmacology in Drug Development, vol. 10, no. 6, pp. 572-581. https://doi.org/10.1002/cpdd.935

APA

Taubel, J., Mazzetti, A., Ferber, G., Burch, W., Fernandes, S., Patel, A., Spencer, C. S., Freier, A., Graff, C., Kanters, J. K., & Camm, J. (2021). A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity. Clinical Pharmacology in Drug Development, 10(6), 572-581. https://doi.org/10.1002/cpdd.935

Vancouver

Taubel J, Mazzetti A, Ferber G, Burch W, Fernandes S, Patel A et al. A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity. Clinical Pharmacology in Drug Development. 2021;10(6):572-581. https://doi.org/10.1002/cpdd.935

Author

Taubel, Jorg ; Mazzetti, Alessandro ; Ferber, Georg ; Burch, William ; Fernandes, Sara ; Patel, Avani ; Spencer, Christopher S. ; Freier, Anne ; Graff, Claus ; Kanters, Jorgen K. ; Camm, John. / A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity. In: Clinical Pharmacology in Drug Development. 2021 ; Vol. 10, No. 6. pp. 572-581.

Bibtex

@article{8f266ad114e346689ad3fb470f5ac7e5,
title = "A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity",
abstract = "Cortexolone 17 alpha-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17 alpha-propionate was found to have a weak inhibitory effect on human Ether-a-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17 alpha-propionate is absorbed. However, the solution formulation developed for the treatment of androgenetic alopecia leads to a measurable systemic concentration and accumulation of the antiandrogen. This phase 1 study assessed the effect of cortexolone 17 alpha-propionate on the QTc interval using concentration-effect analysis and the effect of a meal on QTc to confirm assay sensitivity. Thirty-two volunteers were randomly assigned to receive the active drug or a matching vehicle as placebo. Participants were dosed twice daily on days 1 to 3 (225 mg applied topically as a 7.5% solution 12 hours apart) and once on day 4. Pharmacokinetic and electrocardiogram assessments were performed after supratherapeutic doses. Assay sensitivity was successfully confirmed by using the food effect on the QTc interval. The results of this concentration-QTc analysis demonstrate that cortexolone 17 alpha-propionate and its metabolite/degradation product had no effect on the QTc interval in the concentration range tested.",
keywords = "androgen receptor inhibitor, androgenetic alopecia, antiandrogen, cardiac safety, cortexolone 17&#945, &#8208, propionate, QT interval, ANTIANDROGEN, TIME",
author = "Jorg Taubel and Alessandro Mazzetti and Georg Ferber and William Burch and Sara Fernandes and Avani Patel and Spencer, {Christopher S.} and Anne Freier and Claus Graff and Kanters, {Jorgen K.} and John Camm",
year = "2021",
doi = "10.1002/cpdd.935",
language = "English",
volume = "10",
pages = "572--581",
journal = "Clinical Pharmacology in Drug Development",
issn = "2160-763X",
publisher = "Wiley-Blackwell",
number = "6",

}

RIS

TY - JOUR

T1 - A Phase 1 Study to Investigate the Effects of Cortexolone 17 alpha-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity

AU - Taubel, Jorg

AU - Mazzetti, Alessandro

AU - Ferber, Georg

AU - Burch, William

AU - Fernandes, Sara

AU - Patel, Avani

AU - Spencer, Christopher S.

AU - Freier, Anne

AU - Graff, Claus

AU - Kanters, Jorgen K.

AU - Camm, John

PY - 2021

Y1 - 2021

N2 - Cortexolone 17 alpha-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17 alpha-propionate was found to have a weak inhibitory effect on human Ether-a-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17 alpha-propionate is absorbed. However, the solution formulation developed for the treatment of androgenetic alopecia leads to a measurable systemic concentration and accumulation of the antiandrogen. This phase 1 study assessed the effect of cortexolone 17 alpha-propionate on the QTc interval using concentration-effect analysis and the effect of a meal on QTc to confirm assay sensitivity. Thirty-two volunteers were randomly assigned to receive the active drug or a matching vehicle as placebo. Participants were dosed twice daily on days 1 to 3 (225 mg applied topically as a 7.5% solution 12 hours apart) and once on day 4. Pharmacokinetic and electrocardiogram assessments were performed after supratherapeutic doses. Assay sensitivity was successfully confirmed by using the food effect on the QTc interval. The results of this concentration-QTc analysis demonstrate that cortexolone 17 alpha-propionate and its metabolite/degradation product had no effect on the QTc interval in the concentration range tested.

AB - Cortexolone 17 alpha-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17 alpha-propionate was found to have a weak inhibitory effect on human Ether-a-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17 alpha-propionate is absorbed. However, the solution formulation developed for the treatment of androgenetic alopecia leads to a measurable systemic concentration and accumulation of the antiandrogen. This phase 1 study assessed the effect of cortexolone 17 alpha-propionate on the QTc interval using concentration-effect analysis and the effect of a meal on QTc to confirm assay sensitivity. Thirty-two volunteers were randomly assigned to receive the active drug or a matching vehicle as placebo. Participants were dosed twice daily on days 1 to 3 (225 mg applied topically as a 7.5% solution 12 hours apart) and once on day 4. Pharmacokinetic and electrocardiogram assessments were performed after supratherapeutic doses. Assay sensitivity was successfully confirmed by using the food effect on the QTc interval. The results of this concentration-QTc analysis demonstrate that cortexolone 17 alpha-propionate and its metabolite/degradation product had no effect on the QTc interval in the concentration range tested.

KW - androgen receptor inhibitor

KW - androgenetic alopecia

KW - antiandrogen

KW - cardiac safety

KW - cortexolone 17&#945

KW - &#8208

KW - propionate

KW - QT interval

KW - ANTIANDROGEN

KW - TIME

U2 - 10.1002/cpdd.935

DO - 10.1002/cpdd.935

M3 - Journal article

C2 - 33942574

VL - 10

SP - 572

EP - 581

JO - Clinical Pharmacology in Drug Development

JF - Clinical Pharmacology in Drug Development

SN - 2160-763X

IS - 6

ER -

ID: 286848649