A thorough QT study of guanfacine

Area of Science:

• Pharmacology
• Cardiology
• Clinical Trials

Background:

• Guanfacine extended-release (GXR) is approved for ADHD treatment in pediatric populations.
• A thorough QT study was conducted to evaluate the effect of guanfacine on QT intervals.

Purpose of the Study:

• To assess the potential of guanfacine to prolong QT intervals in healthy adults.
• To determine if guanfacine interferes with cardiac repolarization.

Main Methods:

• A double-blind, 3-period, crossover trial involving 83 healthy adults.
• Participants received immediate-release guanfacine (4 mg and 8 mg), placebo, and moxifloxacin (positive control).
• Continuous ECGs and plasma concentrations were analyzed, with QT intervals corrected using QTcNi and QTcF methods.

Main Results:

• Neither therapeutic nor supra-therapeutic doses of guanfacine prolonged the QT interval (QTcNi analysis).
• The largest 1-sided 95% UCB for QTcF was 10.34 ms at 12 hours post-supratherapeutic dose.
• Most adverse events were mild, with dry mouth and dizziness being most common.

Conclusions:

• Guanfacine does not prolong the QT interval at therapeutic or supra-therapeutic doses when corrected for heart rate.
• Guanfacine is unlikely to interfere with cardiac repolarization in a manner associated with pro-arrhythmic drugs.