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Phase 3 N=132 Randomized Double-blind Treatment

A Study With SAGE-547 for Super-Refractory Status Epilepticus

Super-Refractory Status Epilepticus

Enrolled (actual)
132
Serious AEs
37.1%
Results posted
May 2019
Primary outcome: Primary: Number of Participants Able to be Weaned Off All Third-Line Agents Prior to End of Double-Blind SAGE-547 or Placebo Infusion, and Remain Off All Third-Line Agents for ≥ 24 Hours Following the End of SAGE-547 or Placebo Infusion — 28; 29 Participants — p=0.878

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
SAGE-547 (Drug); Placebo (Drug)
Age
Pediatric, Adult, Older Adult · 2+ yrs
Sex
All
Sponsor
Supernus Pharmaceuticals, Inc.
Primary completion
Jul 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants Able to be Weaned Off All Third-Line Agents Prior to End of Double-Blind SAGE-547 or Placebo Infusion, and Remain Off All Third-Line Agents for ≥ 24 Hours Following the End of SAGE-547 or Placebo Infusion
28; 29 0.878
SECONDARY
Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
13.500; 14.000 0.636
SECONDARY
Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion
45; 38 0.199
SECONDARY
Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
7.000; 15.000 0.328
SECONDARY
Change in Clinical Global Impression Scale (CGI)
6.0; 5.9; -1.0; -0.6; -0.7; -0.5
SECONDARY
Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12
10.05; 11.15; 11.08; 9.23 0.339
SECONDARY
Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12
8.22; 7.50; 7.52; 6.08 0.817
SECONDARY
Number of Separate Episodes of Status Epilepticus Up to Visit 12
1.3; 1.4; 2.2; 1.0 0.567
SECONDARY
Number of Participants With a New Diagnosis of Epilepsy After Visit 11
0; 5; 5; 3

Summary

This is a randomized, double-blind, placebo-controlled trial, designed to evaluate the efficacy and safety of SAGE-547 administered as a continuous intravenous infusion to subjects in Super-Refractory Status Epilepticus (SRSE).

Eligibility Criteria

Inclusion Criteria

  • Subjects two (2) years of age and older
  • Subjects who have:
  • Failed to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial anti-epileptic drug [AED] treatment), according to institution standard of care, and;
  • Failed to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED), according to institution standard of care, and;
  • Not previously been administered a third-line agent but have been admitted to an intensive care unit with the intent of administering at least one third-line agent for at least 24 hours; or who have previously failed zero, one or more wean attempts from third-line agents and are now on continuous intravenous infusions of one or more third-line agent and in an EEG burst or seizure suppression pattern; or who have previously failed one or more wean attempts from third-line agents and are now either not on a continuous intravenous infusion of at least one third-line agent or are on a continuous intravenous infusion of one or more third-line agent but not in an EEG burst or seizure suppression pattern

Exclusion Criteria

  • Subjects with SRSE due to anoxic/hypoxic encephalopathy with highly malignant/ malignant EEG features
  • Children (subjects aged less than 17 years) with an encephalopathy due to a rapidly progressing underlying neurological disorder
  • Subjects who have any of the following:
  • a glomerular filtration rate (GFR) low enough to warrant dialysis but for whatever reason, dialysis is not planned or non-continuous dialysis planned (that would not adequately remove Captisol®);
  • severe cardiogenic or vasodilatory shock requiring two or more pressors that is not related to third-line agent use;
  • fulminant hepatic failure;
  • no reasonable expectation of recovery (for instance, a likely outcome is persistent vegetative state) or life-expectancy, in the experience of the investigator, is less than 30 days.
  • Subjects who are being administered more than three third-line agents concomitantly or in whom the qualifying wean cannot be completed per protocol
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02477618). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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