Convulsive Status EPILEPTICUS, Epilepsy, Non Convulsive Status Epilepticus, Status Epilepticus
Conditions
Brief summary
This study will evaluate the effectiveness and safety of an investigational drug, IV ganaxolone, as adjunctive therapy to standard of care to treat subjects with status epilepticus.
Detailed description
This is a double-blind, randomized, placebo-controlled study to evaluate the safety, tolerability, and efficacy of adjunctive IV ganaxolone in subjects with SE. Study drug will be added to standard of care before IV anesthetic during the treatment of SE. Subjects will be screened for inclusion/exclusion criteria prior to receiving study drug as adjunctive therapy by continuous IV. Subject's will be followed up for 3 weeks post-treatment. Subjects who are known to be at risk for SE may be consented and/or assented prior to an SE event.
Interventions
DRUGIV Ganaxolone active
IV
DRUGIV Placebo, non-active
IV
Sponsors
Marinus Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind study that will randomize subjects to ganaxolone or placebo in a 1:1 ratio as adjunctive therapy to their standard of care.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects 12 years of age and older * Clinical and/or electrographic seizures
Exclusion criteria
* Life expectancy of less than 24 hours * Anoxic brain injury as primary cause of SE * Recent (\<24 hour) traumatic brain injury as the primary cause of SE * Administered anesthesia for the treatment of SE
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment | 24 hours post study drug initiation | Number of participants who did not require an intravenous (IV) Anesthetic Drug (a third-line Treatment) for Status Epilepticus (SE) within the first 24 hours after Study Drug Initiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cessation of SE | Time to SE Cessation, assessed up to 24 hours | Summary of Time to SE Cessation |
| Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE | Drug initiation through follow-up period, up to approximately 4 weeks | Number of participants who Required No Escalation of Treatment for Ongoing or Recurrent SE |
| Number of Participants With No SE Recurrence Per Principal Investigator | Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks. | Number of participants with No SE Recurrence per Principal Investigator within 24hrs of starting treatment, during treatment period (excluding taper), during taper, during 24-hr follow-up period, and during follow-up period. |
| Seizure Burden | Baseline (Pre-dose) to <-24hrs (Post Dose) | Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low - GNX 500 mg/day | 5 |
| Medium - GNX 650 mg/day | 4 |
| High - GNX 713 mg/day | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 0 | 0 |
| Overall Study | Subject discharged to hospice | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Low - GNX | Medium - GNX | High - GNX | Total |
|---|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 25.35 | 62.0 years STANDARD_DEVIATION 18.96 | 53.8 years STANDARD_DEVIATION 17.04 | 56.9 years STANDARD_DEVIATION 19.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 5 | 0 / 4 | 1 / 8 |
| other Total, other adverse events | 5 / 5 | 3 / 4 | 7 / 8 |
| serious Total, serious adverse events | 2 / 5 | 2 / 4 | 2 / 8 |
Outcome results
Primary
Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment
Number of participants who did not require an intravenous (IV) Anesthetic Drug (a third-line Treatment) for Status Epilepticus (SE) within the first 24 hours after Study Drug Initiation.
Time frame: 24 hours post study drug initiation
Population: Safety Population: included all participants who received at least one dose of IV ganaxolone (GNX).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low - GNX | Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment | 5 Participants |
| Medium - GNX | Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment | 4 Participants |
| High - GNX | Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment | 8 Participants |
Secondary
Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE
Number of participants who Required No Escalation of Treatment for Ongoing or Recurrent SE
Time frame: Drug initiation through follow-up period, up to approximately 4 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low - GNX | Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE | 3 Participants |
| Medium - GNX | Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE | 3 Participants |
| High - GNX | Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE | 8 Participants |
Secondary
Number of Participants With No SE Recurrence Per Principal Investigator
Number of participants with No SE Recurrence per Principal Investigator within 24hrs of starting treatment, during treatment period (excluding taper), during taper, during 24-hr follow-up period, and during follow-up period.
Time frame: Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks.
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During taper | 3 Participants |
| Low - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During 24-hr follow-up period | 3 Participants |
| Low - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | Within 24hrs of starting treatment | 5 Participants |
| Low - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During follow-up period | 1 Participants |
| Low - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During treatment period (excluding taper) | 3 Participants |
| Medium - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During taper | 2 Participants |
| Medium - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | Within 24hrs of starting treatment | 4 Participants |
| Medium - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During treatment period (excluding taper) | 4 Participants |
| Medium - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During 24-hr follow-up period | 3 Participants |
| Medium - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During follow-up period | 3 Participants |
| High - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During follow-up period | 7 Participants |
| High - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During 24-hr follow-up period | 8 Participants |
| High - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | Within 24hrs of starting treatment | 7 Participants |
| High - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During taper | 7 Participants |
| High - GNX | Number of Participants With No SE Recurrence Per Principal Investigator | During treatment period (excluding taper) | 7 Participants |
Secondary
Seizure Burden
Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point
Time frame: Baseline (Pre-dose) to <-24hrs (Post Dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low - GNX | Seizure Burden | Change from Baseline at >16 to <- 24 Hours Post-Dose | -99.53 Percentage change from baseline | Standard Deviation 0.935 |
| Low - GNX | Seizure Burden | Change from Baseline at >4 to <- 8 Hours Post-Dose | -77.53 Percentage change from baseline | Standard Deviation 17.95 |
| Low - GNX | Seizure Burden | Change from Baseline at 0 to <- 24 Hours Post-Dose | -78.64 Percentage change from baseline | Standard Deviation 15.286 |
| Low - GNX | Seizure Burden | Change from Baseline at 0 to <- 1 Hour Post-Dose | -94.80 Percentage change from baseline | Standard Deviation 8.458 |
| Low - GNX | Seizure Burden | Change from Baseline at >8 to <- 16 Hours Post-Dose | -47.98 Percentage change from baseline | Standard Deviation 38.063 |
| Low - GNX | Seizure Burden | Change from Baseline at 0 to <- 4 Hour Post-Dose | -98.59 Percentage change from baseline | Standard Deviation 2.092 |
| Medium - GNX | Seizure Burden | Change from Baseline at >8 to <- 16 Hours Post-Dose | -53.29 Percentage change from baseline | Standard Deviation 44.49 |
| Medium - GNX | Seizure Burden | Change from Baseline at >16 to <- 24 Hours Post-Dose | -48.25 Percentage change from baseline | Standard Deviation 45.475 |
| Medium - GNX | Seizure Burden | Change from Baseline at 0 to <- 24 Hours Post-Dose | -56.10 Percentage change from baseline | Standard Deviation 42.183 |
| Medium - GNX | Seizure Burden | Change from Baseline at 0 to <- 4 Hour Post-Dose | -71.75 Percentage change from baseline | Standard Deviation 33.498 |
| Medium - GNX | Seizure Burden | Change from Baseline at 0 to <- 1 Hour Post-Dose | -74.63 Percentage change from baseline | Standard Deviation 25.247 |
| Medium - GNX | Seizure Burden | Change from Baseline at >4 to <- 8 Hours Post-Dose | -59.80 Percentage change from baseline | Standard Deviation 48.352 |
| High - GNX | Seizure Burden | Change from Baseline at 0 to <- 24 Hours Post-Dose | -89.06 Percentage change from baseline | Standard Deviation 20.039 |
| High - GNX | Seizure Burden | Change from Baseline at 0 to <- 1 Hour Post-Dose | -84.01 Percentage change from baseline | Standard Deviation 18.862 |
| High - GNX | Seizure Burden | Change from Baseline at 0 to <- 4 Hour Post-Dose | -87.99 Percentage change from baseline | Standard Deviation 21.439 |
| High - GNX | Seizure Burden | Change from Baseline at >4 to <- 8 Hours Post-Dose | -96.58 Percentage change from baseline | Standard Deviation 6.772 |
| High - GNX | Seizure Burden | Change from Baseline at >8 to <- 16 Hours Post-Dose | -93.75 Percentage change from baseline | Standard Deviation 13.306 |
| High - GNX | Seizure Burden | Change from Baseline at >16 to <- 24 Hours Post-Dose | -81.16 Percentage change from baseline | Standard Deviation 47.368 |
Secondary
Time to Cessation of SE
Summary of Time to SE Cessation
Time frame: Time to SE Cessation, assessed up to 24 hours
Population: Safety Population. Only participants were included if seizure was confirmed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Low - GNX | Time to Cessation of SE | 5.000 Minutes |
| Medium - GNX | Time to Cessation of SE | 5.580 Minutes |
| High - GNX | Time to Cessation of SE | 10.16 Minutes |