Clinical Study of Oral Administration of DN-1417, a TRH analog, in Patients with Therapy-Resistant Epilepsy

Abstract

An open dose-finding trial on oral administration of DN-1417 was undertaken to investigate the relationship among dose, efficacy and side effects. 190 patients with severe epilepsy resistant to conventional drug treatment were randomly allocate to two treatment groups of low dose (20mg/day for adult) and high dose (80mg/day for adult). Medication was done at fasting once a day for eight weeks. When a satisfactory response did not occur after the first 4-week treatment and the drug was well tolerated, the dose was doubled in the latter half. The global improvement rating (GIR) was made on a 7-point scale (of “markedly improved”, “moderately improved”, “slightly improved”, “no change”, “slightly worse”, “moderately worse” and “markedly worse”) based on seizure frequency, EEG findings and nonparoxysmal clinical manifestation.
GIR was judged as “moderately to markedly improved” in 16% of the patients of the low dose group and in 14% of the high dose group. It was “slightly to markedly improved” in 48% of the patients of the low dose group and in 55% of the high dose group. Thus there was no dose-related difference in two groups. Furthermore, the dose increase was not associated with any increase in the rate of improvement. The rate of the patients judged as “slightly to markedly improved” by GIR was, however, dosedependently higher (lower dose group: 61%, high dose group: 73%) in those with Lennox syndrome having no history of West syndrome. The incidence of side effects was about 20% in both dose groups.