Reproducibility of QTc interval changes after meal intake

Area of Science:

• Cardiology
• Clinical Pharmacology
• Pharmacodynamics

Background:

• Assessing assay sensitivity for drug-induced QT interval (QTc) changes often relies on detecting QTc decreases post-meal.
• However, the day-to-day consistency of these meal-induced QTc changes has not been thoroughly evaluated.

Purpose of the Study:

• To determine the reproducibility of QTc interval changes following meal intake.
• To compare the reliability of meal-induced QTc changes versus drug-induced QTc changes (moxifloxacin) for assessing assay sensitivity.

Main Methods:

• Utilized Holter recordings from 4 baseline drug-free days in a thorough QT study (157 females, 164 males).
• Measured heart rate and QTc intervals at multiple time-points post-standardized lunch, comparing day-to-day repeatability using normalized coefficients.
• Compared QTc responses to moxifloxacin with QTc responses to meal intake in a subset of subjects.

Main Results:

• The repeatability of QTc decreases after meals was significantly poorer than that of heart rate increases after meals (p<0.0000001).
• While 6% of subjects did not show QTc prolongation with moxifloxacin, a substantial 39% did not exhibit QTc shortening after lunch (p<0.00001).

Conclusions:

• The day-to-day reproducibility of meal-induced QTc changes is limited.
• Meal-induced QTc changes are less powerful for demonstrating QTc assay sensitivity compared to the standard moxifloxacin-based assay.