PMID- 28500678
OWN - NLM
STAT- MEDLINE
DCOM- 20170817
LR  - 20180107
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 58
IP  - 7
DP  - 2017 Jul
TI  - BGG492 as an adjunctive treatment in patients with partial-onset seizures: A 
      12-week, randomized, double-blind, placebo-controlled, phase II dose-titration 
      study with an open-label extension.
PG  - 1217-1226
LID - 10.1111/epi.13771 [doi]
AB  - OBJECTIVES: To evaluate dose-response relationship of BGG492 as add-on therapy to 
      1-3 antiepileptic drugs in patients with partial-onset seizures and to 
      investigate safety and tolerability of BGG492. METHODS: This was a 12-week, 
      randomized, double-blind, placebo-controlled, phase II dose-titration study (core 
      study) with a 30-week, flexible-dose, open-label extension. In the core study, 
      patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, 
      and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. 
      On completion of the core study, eligible patients entered the extension study. 
      Primary outcome measures were total partial seizure frequency per 28 days (core 
      study) and safety and tolerability (extension study). RESULTS: Overall, 93 
      patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]), 
      and 81 (87.1%) completed the core study. Fifty-one patients entered and 43 
      (84.3%) completed the extension study. In the core study, no statistically 
      significant dose-response trend among the BGG492 treatment groups (100 and 
      150 mg) was observed at the 4-week double-blind maintenance period (weeks 7-10); 
      however, there was higher percent reduction in total partial seizure frequency in 
      the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI] 
      -18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse 
      events (AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo 
      groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%] 
      vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During 
      the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the 
      most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9 
      [17.6%]). SIGNIFICANCE: There was no significant dose-response trend in the 
      BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over 
      placebo was observed in the BGG492 150 mg group. Safety and tolerability data 
      were consistent with the known safety profile for BGG492, and no new safety risks 
      were identified.
CI  - Wiley Periodicals, Inc. (c) 2017 International League Against Epilepsy.
FAU - Elger, Christian E
AU  - Elger CE
AD  - Department of Epileptology, University of Bonn, Bonn, Germany.
FAU - Hong, Seung Bong
AU  - Hong SB
AD  - Department of Neurology, Samsung Medical Center, Samsung Advanced Institute for 
      Health Sciences & Technology (SAIHST), Sungkyunkwan University, Samsung 
      Biomedical Research Institute, Seoul, Korea.
FAU - Brandt, Christian
AU  - Brandt C
AUID- ORCID: 0000-0001-8666-1640
AD  - Bethel Epilepsy Center, Mara Hospital, Bielefeld, Germany.
FAU - Mancione, Linda
AU  - Mancione L
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, U.S.A.
FAU - Han, Jackie
AU  - Han J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, U.S.A.
FAU - Strohmaier, Christine
AU  - Strohmaier C
AD  - Novartis Pharma AG, Basel, Switzerland.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170513
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Quinazolinones)
RN  - 7WG1MR7DAR (selurampanel)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anticonvulsants/administration & dosage/adverse effects/*therapeutic use
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Epilepsies, Partial/*drug therapy
MH  - Female
MH  - Germany
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Quinazolinones/administration & dosage/adverse effects/*therapeutic use
MH  - Young Adult
OTO - NOTNLM
OT  - Antiepileptic drugs
OT  - BGG492
OT  - Epilepsy
OT  - Open-label
OT  - Randomized
EDAT- 2017/05/14 06:00
MHDA- 2017/08/18 06:00
CRDT- 2017/05/14 06:00
PHST- 2017/03/28 00:00 [accepted]
PHST- 2017/05/14 06:00 [pubmed]
PHST- 2017/08/18 06:00 [medline]
PHST- 2017/05/14 06:00 [entrez]
AID - 10.1111/epi.13771 [doi]
PST - ppublish
SO  - Epilepsia. 2017 Jul;58(7):1217-1226. doi: 10.1111/epi.13771. Epub 2017 May 13.