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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV Ganaxolone active | Experimental | Ganaxolone IV loading dose with continuous infusion (maintenance dose) for 2-4 days followed by an 18-hour taper. |
|
| IV Placebo, non-active | Placebo Comparator | Placebo IV loading dose with continuous infusion (maintenance dose) for 2-4 days followed by an 18-hour taper. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IV Ganaxolone active | Drug | IV |
| |
| IV Placebo, non-active |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 24 hours post study drug initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Cessation of SE | Summary of Time to SE Cessation | Time to SE Cessation, assessed up to 24 hours |
| Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maciej Gasior, MD, PhD | Marinus Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nemours/AI duPont Hospital for Children | Wilmington | Delaware | 19803 | United States | ||
| Nicklaus Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35748707 | Derived | Vaitkevicius H, Ramsay RE, Swisher CB, Husain AM, Aimetti A, Gasior M. Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial. Epilepsia. 2022 Sep;63(9):2381-2391. doi: 10.1111/epi.17343. Epub 2022 Jul 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low - GNX | 500 mg/day |
| FG001 | Medium - GNX | 650 mg/day |
| FG002 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 7, 2019 | Mar 8, 2023 |
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Double-blind study that will randomize subjects to ganaxolone or placebo in a 1:1 ratio as adjunctive therapy to their standard of care.
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| Drug |
IV |
|
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 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. | Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks. |
| Seizure Burden | Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point | Baseline (Pre-dose) to <-24hrs (Post Dose) |
| Miami |
| Florida |
| 33155 |
| United States |
| Grady Hospital | Atlanta | Georgia | 30303 | United States |
| Oschner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Duke Medical Center | Durham | North Carolina | 27710 | United States |
| Allegheny General Hospital | Pittsburgh | Pennsylvania | 15212 | United States |
| High - GNX |
713 mg/day |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Low - GNX | 500 mg/day |
| BG001 | Medium - GNX | 650 mg/day |
| BG002 | High - GNX | 713 mg/day |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Population: included all participants who received at least one dose of IV ganaxolone (GNX). | Posted | Count of Participants | Participants | 24 hours post study drug initiation |
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| ||||||||||||||||||||||||||||||||
| Secondary | Time to Cessation of SE | Summary of Time to SE Cessation | Safety Population. Only participants were included if seizure was confirmed. | Posted | Median | Full Range | Minutes | Time to SE Cessation, assessed up to 24 hours |
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| ||||||||||||||||||||||||||||||||
| 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 | Safety Population | Posted | Count of Participants | Participants | Drug initiation through follow-up period, up to approximately 4 weeks |
|
| |||||||||||||||||||||||||||||||||
| 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. | Safety Population | Posted | Count of Participants | Participants | Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks. |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Seizure Burden | Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point | Safety Population | Posted | Mean | Standard Deviation | Percentage change from baseline | Baseline (Pre-dose) to <-24hrs (Post Dose) |
|
|
Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Low - GNX | 500 mg/day | 2 | 5 | 2 | 5 | 5 | 5 |
| EG001 | Medium - GNX | 650 mg/day | 0 | 4 | 2 | 4 | 3 | 4 |
| EG002 | High - GNX | 713 mg/day | 1 | 8 | 2 | 8 | 7 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sedation | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Loss of consciousness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Intestinal perforation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Multiple fractures | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Endotracheal intubation | Surgical and medical procedures | MedDRA 21.0 | Systematic Assessment |
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| Withdrawal of life support | Surgical and medical procedures | MedDRA 21.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Sedation | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
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| Hypercaprnia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
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2 deaths during the follow-up were extracted from the SAE reconciliation database.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marinus Clinical Trials Submission Manager | Marinus Pharmaceuticals, Inc. | 484-801-4670 | clinicaltrials@marinuspharma.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 4, 2020 | Mar 8, 2023 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D013226 | Status Epilepticus |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D012640 | Seizures |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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