臨床研究等提出・公開システム

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE FINDING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PADSEVONIL AS ADJUNCTIVE TREATMENT OF FOCAL-ONSET SEIZURES IN ADULT SUBJECTS WITH DRUG-RESISTANT EPILEPSY

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE FINDING STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PADSEVONIL AS ADJUNCTIVE TREATMENT OF FOCAL-ONSET SEIZURES IN ADULT SUBJECTS WITH DRUG-RESISTANT EPILEPSY

411

The mean age (Standard Deviation) at enrollment was 40.0 years (12.9) for the Placebo group, and 42.5 years (11.6), 36.9 years (13.1), 40.9 years (12.0), 38.8 years (12.1) for PSL 50mg bid, 100mg bid, 200mg bid, 400mg bid. The majority of study participants in both the Placebo and PSL groups was female (57.8% and 57.0%, respectively).

A total of 411 participants were randomized to receive 1 of the 4 doses of PSL (PSL 50mg bid [81 participants], PSL 100mg bid [83 participants], PSL 200mg bid [82 participants], and PSL 400mg bid [82 participants]) or placebo (83 participants). Overall, a total of 89 participants (21.7%) discontinued the study: 15 participants (18.5%) in the PSL 50mg bid group, 15 participants (18.1%) in the PSL 100mg bid group, 21 participants (25.6%) in the PSL 200mg bid group, 24 participants (29.3%) in the PSL 400mg bid group, and 14 participants (16.9%) in the placebo group. Overall, the most common reason for discontinuation was due to an AE (60 participants [14.6%]); discontinuation due to AEs showed a dose-dependent relationship, with the PSL 400mg bid group having the highest number of discontinuations overall (21 participants [25.6%]). Of the 411 randomized participants, 310 participants (75.4%) completed the Conversion Period and entered the OLE study.

Overall, PSL was generally well tolerated and the safety profile was as expected, based on its pharmacology, and was consistent with previous experience with PSL. The incidence of overall TEAEs was generally similar across the 50mg bid, 100mg bid, and 200mg bid doses of PSL, and was higher in the PSL 400mg bid group. The most frequently reported TEAEs during the 16-week Treatment Period were somnolence, dizziness, fatigue, and headache across all treatment groups.

For the change in observable focal-onset seizure frequency from Baseline over the 12-week Maintenance Period, numerical improvements in the least squares (LS) mean change from Baseline were observed for all PSL dose groups (range: -0.41 to -0.49) that were larger than the improvement in the placebo group (-0.28); however, these improvements did not show a dose-dependent relationship.

For 75% responder rates for observable focal-onset seizure frequency from Baseline over the 12 week Maintenance Period, nominally greater 75% responder rates were observed for all PSL dose groups (range: 11.1% to 16.0%) compared with the placebo group (6.2%), and no dose dependent relationship was observed across treatment groups.

The primary efficacy variable, the change in observable focal-onset seizure frequency from Baseline over the 12-week Maintenance Period, was not statistically significant compared with placebo in any PSL dose group. Overall, PSL was generally well tolerated and the safety profile was as expected, based on the pharmacology of the AED, and was consistent with previous experience with PSL.

No

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

CTR_SCC_UCBJapan@UCB.com

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

-

CTR_SCC_UCBJapan@UCB.com

completed

Sept. 03, 2018

Interventional

multicenter, randomized, double-blind, placebo-controlled, parallel-group study

treatment purpose

2

1) Subject fulfills diagnostic criteria for epilepsy and has observable focal-onset (IA1, IB, and IC) seizures for at least 3 years at the time of enrolment (according to the ILAE Classification of Epileptic Seizures, 1981)
2) Subject is currently treated with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit (Visit 1).
3) Subjects having on average 4 and more spontaneous and observable focal-onset seizures per 28 days.

1) Subject has a history of or signs of generalized or combined generalized and focal epilepsy
2) Subject has a history of status epilepticus within the 6-month period prior to Screening Visit (Visit 1).
3) Subject has seizures on a regular basis that are uncountable eg due to clustering during the 8-week retrospective Baseline and during the 4-week Baseline Period.
4) Subject is currently treated with carbamazepine, phenytoin, primidone, or phenobarbital.

Both

Epilepsy and epilepsy syndrome

investigational material(s)
Generic name etc : padsevonil
INN of investigational material : padsevonil
Therapeutic category code : 113 Antiepileptics
Dosage and Administration for Investigational material : Oral administration

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : -

efficacy
Efficacy variable is the change in log transformed observable focal onset seizure frequency from Baseline, over the 12-week Maintenance Period.

safety
efficacy
- The 75% responder rate, where a responder is a subject experiencing a 75% and more reduction in observable focal-onset seizure frequency from Baseline, over the 12-week Maintenance Period.
- Incidence of TEAEs

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June. 22, 2018