Verinurad does not prolong QTc interval: a thorough QT study using concentration-QTc modelling.

Area of Science:

• Pharmacology
• Cardiology
• Clinical Trials

Background:

• Verinurad is a novel urate anion exchanger 1 inhibitor used to lower serum urate levels.
• It is typically co-administered with a xanthine oxidase inhibitor, such as allopurinol.
• Evaluating potential drug interactions, particularly cardiac effects, is crucial for novel therapeutics.

Purpose of the Study:

• To assess the potential for QT interval prolongation when verinurad is co-administered with allopurinol.
• To determine the cardiac safety profile of verinurad in combination therapy.

Main Methods:

• A randomized, double-blind, placebo-controlled, crossover thorough QT/QTc (TQT) study (NCT04256629) was conducted in 24 healthy volunteers.
• Participants received single doses of verinurad (extended and immediate release) with allopurinol, or placebos.
• The primary endpoint was the change in Fridericia-corrected QTcF interval (ΔΔQTcF) using a concentration-QTc model.

Main Results:

• The estimated ΔΔQTcF at the highest clinically relevant verinurad exposure was -2.7 msec (90% CI: -4.6, -0.8).
• The upper bound of the 90% CI for ΔΔQTcF remained below the 10 msec threshold at all observed concentrations.
• A supratherapeutic dose of verinurad was used to achieve exposures eightfold higher than clinically relevant levels.

Conclusions:

• Verinurad in combination with allopurinol does not induce QTcF prolongation at the highest clinically relevant exposures.
• The observed effect on ΔΔQTcF was below the threshold for regulatory concern.
• This suggests a favorable cardiac safety profile for the verinurad-allopurinol combination.