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Clinical Trial
. 2021 Mar 25;13(4):235.
doi: 10.3390/toxins13040235.

Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Dose Finding Trial

Samuel A Goldlust  1 , Mojgan Kavoosi  2 , Jennifer Nezzer  3 , Mehran Kavoosi  2 , Walter Korz  2 , Kenneth Deck  4
Affiliations
Clinical Trial

Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Dose Finding Trial

Samuel A Goldlust et al. Toxins (Basel). .

Abstract

Tetrodotoxin (TTX) has emerged as a potentially efficacious agent for chemotherapy-induced neuropathic pain (CINP), a prevalent, debilitating condition often resistant to analgesics. This randomized, double-blind, dose-finding study was undertaken to explore safety and trends in efficacy of four TTX doses and to identify a dose for further study. One hundred and twenty-five patients with taxane- or platinum-related CINP received subcutaneous placebo or TTX (7.5 µg twice daily (BID), 15 µg BID, 30 µg once daily (QD), 30 µg BID) for four consecutive days. Primary outcome measure was average patient-reported Numeric Pain Rating Scale (NPRS) score during Days 21-28 post-treatment. Changes in mean NPRS score were not statistically different between cohorts, due to small trial size and influence of a few robust placebo responders. Cumulative responder analysis showed significant difference from placebo with 30 µg BID cohort using the maximum response at any timepoint (p = 0.072), 5-day (p = 0.059), 10-day (p = 0.027), and 20-day (p = 0.071) rolling averages. In secondary quality of life (QOL) outcomes, 30 µg BID cohort also differed significantly from placebo in a number of SF-36 and CIPN20 subscales. Most adverse events (AE) were mild or moderate with oral paresthesia (29.6%) and oral hypoesthesia (24.8%) as most common.

Keywords: analgesic; chemotherapy induced neuropathic pain; clinical trial; pain; peripheral neuropathy; tetrodotoxin; voltage-gated sodium channels.

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Conflict of interest statement

Goldlust received research support from the sponsor for conduct of the clinical trial, as well as support for travel and honoraria as a consultant for trial-related regulatory meetings. Deck received research support from the trial sponsor for conduct of the clinical trial. Nezzer received support from the trial sponsor to perform additional post hoc analysis.

Figures

Figure 1
Figure 1
Cumulative responder analysis with all data from the single site removed. The p-value represents the significant difference from placebo of 30 µg BID (twice daily TTX) cohort using the maximum response of the cumulative averages.
Figure 2
Figure 2
Participant disposition and trial profile.
See this image and copyright information in PMC

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