Drug Development

Area of Science:

• Pharmacology
• Cardiology
• Neuroscience

Background:

• Psychotropic medications can prolong the QT interval, a critical cardiac measurement.
• ACP-204, a selective serotonin 2A inverse agonist/antagonist, was developed to treat Alzheimer's disease psychosis with a potentially improved safety profile.
• This study investigated ACP-204's effect on corrected QT (QTc) intervals and its concentration-effect relationship.

Purpose of the Study:

• To evaluate the effect of single oral doses of ACP-204 on corrected QT (QTc) intervals in healthy volunteers.
• To assess the relationship between plasma ACP-204 concentrations and time-matched changes in QTc intervals.
• To determine if ACP-204 poses a risk for QT prolongation, a known adverse event of psychotropic drugs.

Main Methods:

• Phase 1, randomized, placebo-controlled, double-blind study.
• Single ascending oral doses of ACP-204 (10-180 mg) or placebo administered to healthy adults.
• 12-lead electrocardiograms (ECG) used to measure changes in Friderica-corrected QT (ΔQTcF) intervals from baseline.
• Concentration-effect modeling to analyze drug concentration and ΔQTcF relationship.

Main Results:

• No participant exhibited a QTcF interval exceeding 450 ms across all dose groups.
• Minor, benign changes in QTcF were observed, with no clear dose-response pattern.
• Concentration-effect modeling showed small, clinically insignificant placebo-adjusted ΔQTcF, with the upper confidence limit below 10 ms.

Conclusions:

• Single-dose administration of ACP-204 (10-180 mg) did not result in meaningful increases in QTcF intervals.
• ACP-204 demonstrated no QTcF prolongation at doses up to 180 mg in healthy participants.
• The findings support ACP-204's favorable cardiac safety profile concerning QT interval duration.