Evaluation of Eluxadoline Effect on Cardiac Repolarization

Area of Science:

• Pharmacology
• Cardiology
• Clinical Trials

Background:

• Eluxadoline is a mixed μ-opioid receptor (OR) agonist and κ-OR antagonist.
• Cardiac repolarization is a critical aspect of cardiac electrophysiology.
• Assessing drug effects on QT intervals is crucial for cardiovascular safety.

Purpose of the Study:

• To evaluate the effects of eluxadoline on cardiac repolarization.
• To determine if eluxadoline prolongs QT intervals at therapeutic and supratherapeutic doses.
• To assess the safety and tolerability of eluxadoline in relation to cardiac function.

Main Methods:

• An evaluator-blinded, placebo- and positive-controlled, 4-period crossover study.
• Healthy volunteers received single oral doses of eluxadoline (100 mg or 1000 mg), moxifloxacin, or placebo.
• QT intervals were corrected using individual custom correction (QTcI) and analyzed for changes from baseline (ΔΔQTcI).

Main Results:

• Moxifloxacin demonstrated assay sensitivity with a ΔΔQTcI of 11.94 ms.
• The maximum ΔΔQTcI for eluxadoline 1000 mg was 4.10 ms (95% upper bound 5.81 ms).
• The maximum ΔΔQTcI for eluxadoline 100 mg was 1.20 ms (95% upper bound 2.91 ms), with no significant gender effects.

Conclusions:

• Eluxadoline did not significantly prolong QT intervals at therapeutic or supratherapeutic doses.
• Eluxadoline was found to be safe and generally well-tolerated in healthy volunteers.
• The study confirms the cardiovascular safety profile of eluxadoline concerning cardiac repolarization.