LAUSR

Background Macrolide antibiotics may cause QT prolongation. Objectives To study the QT effect of a novel macrolide, solithromycin. Methods This was a thorough QT study with a three-way crossover design performed in healthy male and female subjects to evaluate the ECG effects of a novel macrolide, solithromycin. Forty-eight subjects were randomized to receive 800 mg of intravenous (iv) solithromycin, 400 mg of oral moxifloxacin and placebo in three separate treatment periods. Continuous 12 lead ECGs were recorded at a pre-dose baseline and serially after drug administration for 24 h. Results After the 40 min infusion of 800 mg of solithromycin, the geometric mean solithromycin peak plasma concentration (Cmax) reached 5.9 (SD: 1.30) &mgr;g/mL. Solithromycin infusion caused a heart rate increase with a peak effect of 15 bpm immediately after the end of the infusion. The change-from-baseline QTcF (&Dgr;QTcF) was similar after dosing with solithromycin and placebo and the resulting placebo-corrected &Dgr;QTcF (&Dgr;&Dgr;QTcF) for solithromycin was therefore small at all timepoints with a peak effect at 4 h of only 2.8 ms (upper bound of the 90% CI: 4.9 ms). Using a linear exposure–response model, a statistically significant, slightly negative slope of −0.86 ms per ng/mL (90% CI: −1.19 to −0.53; P = 0.0001) was observed with solithromycin. The study's ability to detect small QT changes was confirmed by the moxifloxacin response. Solithromycin did not have a clinically meaningful effect on the PR or QRS interval. Conclusions The study demonstrated that solithromycin, unlike other macrolide antibiotics, does not cause QT prolongation.