Table 3.

Summary of the analgesic effect of TTX on clinical trials.

Patients	Administration	Doses	Type of Study	Results	Main Adverse Events	References
24	s.c. injections	15–90  μg	Open-label study for severe cancer pain	17 of 31 treatments resulted in clinically meaningful reductions in pain intensity, and relief of pain persisted for up to two weeks or longer	Perioral tingling or other mild sensory phenomena	[75]
82	s.c. injections	30  μg	Placebo-controlled trial for moderate to severe cancer pain	Non-statistically significant trend toward more responders in the TTX arm (42%) vs. placebo arm (31%)	Transient ataxia, mild and related to tingling, numbness, or other transient sensory symptoms	[76]
45	s.c. injections	30  μg	Open-label study for cancer pain	47% met the criteria for “responder”	Mild peri-oral tingling or numbness, transient nausea, irritation	[77]
165	s.c. injections	30 μg	Phase III randomized, double-blind, placebo-controlled clinical trial for moderate to severe cancer pain	Clinical benefit of TTX over placebo based on the pain endpoint alone with a clinically significant estimated effect size of 16.2% (p = 0.0460)	Nausea, dizziness, and oral numbness or tingling, generally mild to moderate and transient	[78]
125	s.c. injections	7.5, 15, 30  μg	Phase II randomized, double-blind, placebo controlled trial for chemotherapy-induced neuropathic pain	Changes in pain score were not statistically different between cohorts, due to small trial size and influence of a few robust placebo responders	Mild or moderate oral paresthesia (29.6%) and oral hypoesthesia (24.8%)	[79]