PMID- 28230252
OWN - NLM
STAT- MEDLINE
DCOM- 20170626
LR  - 20180107
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 58
IP  - 4
DP  - 2017 Apr
TI  - Randomized, double-blind, placebo-controlled phase 2 study of ganaxolone as 
      add-on therapy in adults with uncontrolled partial-onset seizures.
PG  - 558-564
LID - 10.1111/epi.13705 [doi]
AB  - OBJECTIVE: To evaluate the efficacy and safety of ganaxolone as adjunctive 
      therapy in adults with uncontrolled partial-onset seizures despite taking up to 
      three concomitant antiepileptic drugs (AEDs). METHODS: Adults aged 18-69 years 
      and refractory to conventional AEDs were enrolled in a multicenter, double-blind, 
      placebo-controlled trial. After an 8-week baseline period, patients were 
      randomized 2:1 to ganaxolone 1,500 mg/day or placebo for a 10-week treatment 
      period (2-week forced titration and 8-week maintenance) followed by either 
      tapering or entry into an open-label extension study. The primary endpoint was 
      mean weekly seizure frequency. Secondary endpoints included the proportion of 
      patients experiencing >/=50% reduction in seizure frequency (responder rate), 
      percent change in mean weekly seizure frequency, seizure-free days, and quality 
      of life. Safety and tolerability assessments included adverse events (AEs), 
      treatment discontinuation, and clinical laboratory evaluations. Efficacy analyses 
      were performed on the intent-to-treat population. RESULTS: Of 147 randomized 
      patients (98 ganaxolone, 49 placebo), 131 completed the study; 95% of 
      participants titrated up to 1,500 mg/day and 78% maintained this dose. From 
      baseline to endpoint, mean weekly seizure frequency decreased with ganaxolone 
      (6.5-5.2) versus placebo (9.2-10.8), representing an 11.4% decrease versus 
      placebo (p = 0.0489, analysis of covariance [ANCOVA]). Mean percent change from 
      baseline was -17.6% with ganaxolone versus 2.0% with placebo (p = 0.0144, 
      Kruskal-Wallis test). Responder rates were 24% with ganaxolone versus 15% with 
      placebo (p = 0.19). Discontinuation due to adverse events was similar with 
      ganaxolone (7.1%) and placebo (6.1%). Common adverse events were mild to moderate 
      in severity and included dizziness (16.3% vs. 8.2%), fatigue (16.3% vs. 8.2%), 
      and somnolence (13.3% vs. 2.0%). SIGNIFICANCE: Ganaxolone 1,500 mg/day reduced 
      partial-onset seizure frequency and was generally safe and well tolerated in this 
      phase 2 study. These results support continued development of ganaxolone for 
      adult patients with refractory partial-onset seizures.
CI  - Wiley Periodicals, Inc. (c) 2017 International League Against Epilepsy.
FAU - Sperling, Michael R
AU  - Sperling MR
AD  - Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, 
      Philadelphia, Pennsylvania, U.S.A.
FAU - Klein, Pavel
AU  - Klein P
AD  - Mid-Atlantic Epilepsy and Sleep Center, Bethesda, Maryland, U.S.A.
FAU - Tsai, Julia
AU  - Tsai J
AD  - Marinus Pharmaceuticals, Radnor, Pennsylvania, U.S.A.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170223
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 98WI44OHIQ (ganaxolone)
RN  - BXO86P3XXW (Pregnanolone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Anticonvulsants/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pregnanolone/*analogs & derivatives/therapeutic use
MH  - Seizures/*drug therapy
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Adjunctive therapy
OT  - Ganaxolone
OT  - Neurosteroid
OT  - Partial-onset seizures
EDAT- 2017/02/24 06:00
MHDA- 2017/06/27 06:00
CRDT- 2017/02/24 06:00
PHST- 2017/01/18 00:00 [accepted]
PHST- 2017/02/24 06:00 [pubmed]
PHST- 2017/06/27 06:00 [medline]
PHST- 2017/02/24 06:00 [entrez]
AID - 10.1111/epi.13705 [doi]
PST - ppublish
SO  - Epilepsia. 2017 Apr;58(4):558-564. doi: 10.1111/epi.13705. Epub 2017 Feb 23.