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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
1/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2016
Sample size
Target
Accrual to date
Final
405
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.

Results are available at https://clinicaltrials.gov/study/NCT01963208