Dezinamide for partial seizures: results of an n-of-1 design trial.
BACKGROUND
Dezinamide (DZM, ADD 94057) is a potential antiepileptic drug that binds to the voltage-sensitive sodium channel and showed preliminary evidence of efficacy and safety in an open-label study.


METHODS
Our double-blind, placebo-controlled trial at two sites used an n-of-1 (single-patient) design. All 15 patients had medically intractable partial-onset seizures and were comedicated with phenytoin (PHT) only. Treatment was for six 5-week periods (three active paired with three placebo in random sequence). Assuming nonlinear kinetics, we used an initial pharmacokinetic profile to estimate dosages for reaching target plasma concentrations of DZM.


RESULTS
Statistically significant seizure reduction was found by both a randomization test (p = 0.0025) and a signed rank test (p = 0.048). Median seizure frequency decreased 37.9%, and 40% of patients had > 50% seizure reduction, both compared with placebo. Pharmacokinetic predictions were not accurate; mean plasma concentrations fell well below target values. Plasma PHT concentrations increased (mean = 17.1%) during DZM treatment. The most common adverse experiences were fatigue, light-headedness, and abnormal gait; five patients required DZM dosage reductions.


CONCLUSIONS
DZM showed minimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establishes the suitability of the n-of-1 design to investigational antiepileptic drug trials.
Privitera
M D
MD
Department of Neurology, University of Cincinnati Medical Center, OH 45267.
Treiman
D M
DM
Pledger
G W
GW
Sahlroot
J T
JT
Handforth
A
A
Linde
M S
MS
France
C R
CR
Cereghino
J J
JJ
McCutchen
C B
CB
Wood
J H
JH
D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D001384:Azetidines / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants; D001384:Azetidines; C064672:AHR 11748