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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01963208




Registration number
NCT01963208
Ethics application status
Date submitted
11/10/2013
Date registered
16/10/2013
Date last updated
14/02/2023

Titles & IDs
Public title
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures and Open-label Extension
Scientific title
A Multicenter, Double Blind, Randomized, Placebo-Controlled Trial to Determine the Efficacy and Safety of Ganaxolone as Adjunctive Therapy for Adults With Drug-Resistant Partial-Onset Seizures Followed by Long-term Open-Label Treatment
Secondary ID [1] 0 0
1042-0603
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drug Resistant Partial Onset Seizure 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ganaxolone
Treatment: Drugs - Placebo

Experimental: Double Blind - Cohort 1 - Ganaxolone - 1200 mg/day and 1800 mg/day + AED

Placebo comparator: Double Blind - Cohort 1 - Placebo - Placebo + AED

Experimental: Open Label - Ganaxolone in Double-blind phase - 1800 mg/day + AED

Experimental: Double Blind - Cohort 2 - Ganaxolone - 1800 mg/day + AED

Placebo comparator: Double Blind - Cohort 2 - Placebo - Placebo +AED

Experimental: Open Label - Placebo in Double-blind phase - 1800 mg/day + AED


Treatment: Drugs: ganaxolone
200 mg and 225 mg capsules; target dose 1800 mg/day dosed 900mg 2x/day

Treatment: Drugs: Placebo
placebo

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Timepoint [1] 0 0
Baseline and Week 14
Secondary outcome [1] 0 0
Double Blind: Cohort 2: Number of Participants With =50% Responder Rate During Titration + Maintenance Period
Timepoint [1] 0 0
Up to Week 14
Secondary outcome [2] 0 0
Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Titration + Maintenance Period
Timepoint [2] 0 0
Baseline and Week 14
Secondary outcome [3] 0 0
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 14
Timepoint [3] 0 0
At Week 14
Secondary outcome [4] 0 0
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Timepoint [4] 0 0
Baseline and Week 2 to Week 14
Secondary outcome [5] 0 0
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Titration + Maintenance Period
Timepoint [5] 0 0
Baseline and Week 14
Secondary outcome [6] 0 0
Double Blind: Cohort 2: Change From Baseline in 28-day Seizure Frequency During Maintenance Period
Timepoint [6] 0 0
Baseline and Week 2 to Week 14
Secondary outcome [7] 0 0
Double Blind: Cohort 2: Change From Baseline in the Number of Seizure Free Days Per 28-day Period During Maintenance Period
Timepoint [7] 0 0
Baseline and Week 2 to Week 14
Secondary outcome [8] 0 0
Double Blind: Cohort 2: Percentage of Responders Experiencing a =R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Titration + Maintenance Period
Timepoint [8] 0 0
Up to Week 14
Secondary outcome [9] 0 0
Double Blind: Cohort 2: Percentage of Responders Experiencing a =R% (80%, 60%, 40%, and 20%) Reduction From Baseline to the End of Treatment Period in 28-day Seizure Frequency During Maintenance Period
Timepoint [9] 0 0
Week 2 to Week 14
Secondary outcome [10] 0 0
Double Blind: Cohort 2: Percentage of Seizure Free Participants During the Maintenance Period
Timepoint [10] 0 0
Week 2 to Week 14
Secondary outcome [11] 0 0
Double Blind: Cohort 2: Percentage of Participants Who Experienced at Least One 28-day Seizure Free Period During Titration + Maintenance Phase
Timepoint [11] 0 0
Up to Week 14
Secondary outcome [12] 0 0
Double Blind: Cohort 2: Longest Percent of Time Spent Seizure-free During Titration + Maintenance Period
Timepoint [12] 0 0
Up to Week 14
Secondary outcome [13] 0 0
Double Blind: Cohort 2: Percent Change From Baseline in 28-day Seizure Frequency for Different Subtypes of Seizures During Titration + Maintenance Period
Timepoint [13] 0 0
Baseline and Week 14
Secondary outcome [14] 0 0
Double Blind: Cohort 2: Number of Participants With Patient Global Impression of Change - Improvement (PGI-I) at Week 8 and Week 14
Timepoint [14] 0 0
Week 8 and Week 14
Secondary outcome [15] 0 0
Double Blind: Cohort 2: Number of Participants With Clinical Global Impression of Change - Improvement (CGI-I) at Week 8
Timepoint [15] 0 0
At Week 8

Eligibility
Key inclusion criteria
* Able to give informed consent in writing, or have a legally authorized representative able to do so
* Willing to enter and participate for the full term of the double blind phase and willing to enter into the open-label phase
* Male or female outpatients > 18 years of age
* Have a confident diagnosis of drug-resistant epilepsy with partial-onset seizures (POS), with or without secondary generalization, for =2 years. Have residual POS despite having been treated in the past with at least 2 approved anti-epilepsy drugs (AEDs) either alone or in combination
* Based on history, participants would be anticipated to have at least 3 POS during each 4-week Baseline period and unlikely to have 21 or more consecutive POS-free days
* Currently being treated and maintained with a stable regimen of 1, 2, or 3 AEDs
* Able and willing to maintain daily seizure calendar
* Able and willing to take drug with food twice daily
* Sexually active women of childbearing potential must use acceptable birth control and have a negative pregnancy test at all visits
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have had previous exposure to ganaxolone
* Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds
* Exposure to any investigational drug or device <30 days prior to screening, or plans to take another investigational drug at any time during the study
* Time of onset of epilepsy treatment <2 years prior to enrollment
* Have generalized epilepsy, such as Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, absence epilepsy, or non-epileptic seizures within the last 12- month period prior to study entry
* Have less than 3 POS seizures in a 28-day period or more than 21 consecutive seizure-free days during the Baseline period
* Have only simple partial seizures without any observable motor component
* Have innumerable seizures or status epilepticus within the last 12-months prior to screening
* Have more than 100 POS per 4-week Baseline period
* Have seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system (CNS) disease deemed progressive, metabolic illness, or progressive degenerative disease
* Current use of vigabatrin is not permitted. If prior use of vigabatrin, must have documented stable visual fields
* Current use of ezogabine is not permitted. If prior use, must have been off the medication for at least 3 months prior to screening and have had documented normal fundoscopic exam by ophthalmologist
* Are planning surgery, or to be evaluated for surgery, during the double-blind phase to control seizures including VNS implantation
* Are suffering from acute or progressive neurological disease, moderate or severe psychiatric disease, or severe mental abnormalities that are likely to require changes in drug therapy during the double-blind portion of the study or interfere with the objectives of the study or the ability to adhere to the protocol requirements
* Have a history of an actual suicide attempt in the last 5 years or more than 1 lifetime suicide attempt
* Have a positive urine drug screen at Screening or meet criteria for current or historical Substance Use Disorder (DSM-V criteria) within the past 5 years.
* Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect participant safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs
* Have elevated ALT (SGPT) or AST (SGOT) greater than 3 times upper limits of normal, or total bilirubin greater than 1.5 times ULN
* Have a history of malignancy within the past 2 years, with the exception of basal cell carcinoma
* Are currently following or planning to follow a ketogenic diet
* Use of dietary supplements or herbal preparations are not permitted if participant has been using them consistently for less than 6 months prior to screening, or does not plan on remaining on stable doses for the duration of the double blind phase. Use of St. John's Wort is not permitted
* Females who are pregnant, currently breastfeeding or planning to become pregnant during the duration of the study
* A history of chronic noncompliance with drug regimens
* Inability to withhold grapefruit and grapefruit juice from diet during the entire clinical trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
The Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
Flinders Medical Center - Bedford Park
Recruitment hospital [5] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [6] 0 0
The Florey Institute of Neuroscience and Mental Health - Heidelberg
Recruitment hospital [7] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oklahoma
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Blagoevgrad
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Pleven
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Ruse
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Sofia
Country [25] 0 0
Bulgaria
State/province [25] 0 0
Varna
Country [26] 0 0
Germany
State/province [26] 0 0
Bernau
Country [27] 0 0
Germany
State/province [27] 0 0
Bielefeld
Country [28] 0 0
Germany
State/province [28] 0 0
Bonn
Country [29] 0 0
Germany
State/province [29] 0 0
Dussseldorf
Country [30] 0 0
Germany
State/province [30] 0 0
Marburg
Country [31] 0 0
Germany
State/province [31] 0 0
Ulm
Country [32] 0 0
Poland
State/province [32] 0 0
Jaworowa
Country [33] 0 0
Poland
State/province [33] 0 0
Katowice
Country [34] 0 0
Poland
State/province [34] 0 0
Lublin
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Kazan
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Moscow
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Nizhniy Novgorod
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Novosibirsk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Saint Petersburg
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Samara
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Yaroslavl

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Marinus Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.