Key result
Subcutaneous tetrodotoxin at doses up to 45 µg was safe, well-tolerated, and did not cause QT prolongation, with the upper bound of the 90% CI for ΔΔQTcF not exceeding 10 ms.
Why the study?
Does tetrodotoxin cause QT prolongation or safety issues in healthy adults?
RCT (n=25)
Double-blind
Randomized
Does tetrodotoxin cause QT prolongation or safety issues in healthy adults?
Single ascending subcutaneous doses of tetrodotoxin up to 45 µg are safe, well-tolerated, and do not cause clinically significant QT prolongation in healthy adults.
Tetrodotoxin (TTX) is a highly specific voltage-gated sodium channel (VGSC) blocker in clinical evaluation as a peripheral-acting analgesic for chronic pain. This study presents the first published results of the safety including cardiac liability of TTX at therapeutic-relevant concentrations in twenty-five healthy adults. Randomized, double-blind, placebo-, and positive- (moxifloxacin) controlled study evaluated single ascending doses of 15 µg, 30 µg, and 45 µg TTX over 3 periods with a 7-day washout between each period. Subcutaneous injections of TTX were readily absorbed, reaching maximum plasma concentration (Cmax) within 1.5 h. Both extent of exposure (AUC) and Cmax increased in proportion to dose. No QT prolongation was identified by concentration-QTc analysis and the upper bounds of the two-sided 90% confidence interval of predicted maximum baseline and placebo corrected QTcF (ΔΔQTcF) value did not exceed 10 ms for all tetrodotoxin doses, thereby meeting the criteria of a negative QT study. Safety assessments showed no clinically relevant changes with values similar between all groups and no subject withdrawing due to adverse events. Paresthesia, oral-paresthesia, headache, dizziness, nausea, and myalgia were the most common TEAEs (overall occurrence ≥5%) in the TTX treatment groups. TTX doses investigated in this study are safe, well-tolerated, and lack proarrhythmic proclivity.
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Kavoosi et al. (2020) conducted an RCT in Healthy adults (n=25). Tetrodotoxin (TTX) vs. Placebo and moxifloxacin was evaluated on Safety, tolerability, pharmacokinetics, and concentration-QTc analysis. Subcutaneous tetrodotoxin at doses up to 45 µg was safe, well-tolerated, and did not cause QT prolongation, with the upper bound of the 90% CI for ΔΔQTcF not exceeding 10 ms.
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