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NEUROLOGY 1994;44:1453
© 1994 American Academy of Neurology

Dezinamide for partial seizures

Results of an n-of-1 design trial

M. D. Privitera, MD, D. M. Treiman, MD, G. W. Pledger, PhD, J. T. Sahlroot, PhD, A. Handforth, MD, M. S. Linde, RN, C. R. France, RN, J. J. Cereghino, MD, C. B. McCutchen, MD and J. H. Wood, PhD

Department of Neurology (Dr. Privitera and C. France), University of Cincinnati Medical Center, Cincinnati, OH; the Department of Neurology (Drs. Treiman and Handforth), UCLA Medical Center, and the Department of Veterans Affairs Medical Center (Drs. Treiman and Handforth), Wadsworth and Brentwood Divisions, Los Angeles, CA; the National Institute of Neurological Disorders and Stroke (Drs. Pledger and Sahlroot, M. Linde, and Drs. Cereghino and McCutchen), Epilepsy Branch, Bethesda, MD; and the Department of Pharmacy (Dr. Wood), Medical College of Virginia, Richmond, VA.

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.

Address correspondence and reprint requests to Dr. Michael Privitera, Department of Neurology (525), University of Cincinnati Medical Center, Cincinnati, OH 45267.

Supported by NINDS Contract Numbers N01-NS-7-2328 (Los Angeles) and N01-NS-8-2306 (Cincinnati).

Received November 3, 1993. Accepted in final form February 10, 1994.






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