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Concentration-QTc Modeling to Support Clinical Development of Fezolinetant
Jace C Nielsen1, Masako Saito2, Xuegong Wang1
1Astellas Pharma Global Development, Inc., IL, USA.
Clinical Pharmacology in Drug Development
|October 19, 2025
Summary
Fezolinetant, a treatment for menopause vasomotor symptoms, does not cause significant QT prolongation. This finding supports its safety profile, eliminating the need for a thorough QT study.
Area of Science:
- Pharmacology
- Cardiovascular Safety
- Neuroendocrinology
Background:
- Fezolinetant is a selective neurokinin-3 receptor antagonist approved for treating vasomotor symptoms of menopause.
- It functions by modulating neuronal activity in the thermoregulatory center.
Purpose of the Study:
- To assess the risk of QT prolongation associated with fezolinetant prior to Phase 3 trials.
- To determine if a thorough QT (TQT) study was necessary for regulatory submission.
Main Methods:
- A concentration-QTc (C-QTc) analysis was conducted using data from a Phase 1 ascending dose study.
- The analysis included single doses up to 900 mg and multiple daily doses up to 720 mg in healthy participants.
- ICH E14 Guideline recommendations were followed.
Main Results:
- The C-QTc analysis revealed no clinically relevant QT prolongation at therapeutic or supra-therapeutic doses of fezolinetant.
- Modeling results indicated a lack of significant cardiovascular risk.
Conclusions:
- Fezolinetant does not pose a clinically relevant risk of QT prolongation.
- The safety data supported waiving the requirement for a thorough QT (TQT) study.
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