Key result
Intravenous solithromycin did not prolong cardiac repolarization in healthy subjects, demonstrating a peak placebo-corrected change in QTcF of 2.8 ms (upper bound of 90% CI: 4.9 ms).
Why the study?
Does solithromycin cause QT prolongation compared to placebo in healthy subjects?
RCT (n=48)
randomized
Does solithromycin cause QT prolongation compared to placebo in healthy subjects?
Solithromycin, a novel macrolide antibiotic, does not cause clinically meaningful QT prolongation, distinguishing it from other drugs in its class.
Supports QT-safe intravenous solithromycin use without monitoring; confirms lack of clinically meaningful repolarization effects versus other macrolides.
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: ) reached 5.9 (SD: 1.30) μg/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 (ΔQTcF) was similar after dosing with solithromycin and placebo and the resulting placebo-corrected ΔQTcF (ΔΔQTcF) 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.
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Darpö et al. (2016) conducted an RCT in Healthy subjects (n=48). Solithromycin vs. Placebo and 400 mg oral moxifloxacin was evaluated on Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) (Peak effect 2.8 ms). Intravenous solithromycin did not prolong cardiac repolarization in healthy subjects, demonstrating a peak placebo-corrected change in QTcF of 2.8 ms (upper bound of 90% CI: 4.9 ms).
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