Trial Outcomes & Findings for A Randomized, Controlled Trial of Ganaxolone in Adult Uncontrolled Partial-Onset Seizures (NCT NCT00465517)

Last Updated: 2023-03-15

Results Overview

Weekly seizure frequency, analyzed as mean weekly log-transformed seizure frequency \[including partial-onset seizures (POS) with or without secondary generalization, but not non-motor simple partial seizure (SPS)\] during Weeks 1 through 10.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

147 participants

Primary outcome timeframe

Week 1 through Week 10

Results posted on

2023-03-15

Participant Flow

No recruitment details specified

Participants were randomized (Visit 4, Week 0, before dosing) to receive investigational product in an active:placebo ratio of 2:1.

Participant milestones

Participant milestones
Measure	Ganaxolone Suspension formulation 50 milligrams per milliliter (mg/mL) three times daily (TID)	Placebo Placebo Suspension 50 mg/mL TID
Overall Study STARTED	98	49
Overall Study COMPLETED	86	45
Overall Study NOT COMPLETED	12	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ganaxolone Suspension formulation 50 milligrams per milliliter (mg/mL) three times daily (TID)	Placebo Placebo Suspension 50 mg/mL TID
Overall Study Adverse Event	7	3
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	4	1

Baseline Characteristics

A Randomized, Controlled Trial of Ganaxolone in Adult Uncontrolled Partial-Onset Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=49 Participants Placebo Suspension 50 mg/mL TID	Total n=147 Participants Total of all reporting groups
Age, Continuous	39.1 years STANDARD_DEVIATION 11.74 • n=5 Participants	40.2 years STANDARD_DEVIATION 11.11 • n=7 Participants	39.5 years STANDARD_DEVIATION 11.51 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	36 Participants n=7 Participants	100 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	13 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=5 Participants	45 Participants n=7 Participants	136 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	87 Participants n=5 Participants	42 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	98 participants n=5 Participants	49 participants n=7 Participants	147 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 1 through Week 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Mean Weekly Log-transformed Seizure Frequency During Weeks 1 Through 10	5.20 log[seizures per week] Standard Deviation 9.286	10.77 log[seizures per week] Standard Deviation 44.156

SECONDARY outcome

Timeframe: Week 3 through Week 10

Population: Only those participants with data available during Weeks 3 to 10 were analyzed.

Weekly seizure frequency, analyzed as mean weekly log-transformed seizure frequency \[including POS with or without secondary generalization, but not non-motor SPS\] during the Weeks 3 through 10

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=46 Participants Placebo Suspension 50 mg/mL TID
Mean Weekly Log-transformed Seizure Frequency During Weeks 3 Through 10	5.44 log[seizures per week] Standard Deviation 9.431	11.90 log[seizures per week] Standard Deviation 50.209

SECONDARY outcome

Timeframe: Baseline and at Week 1 through Week 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed.

Summary of change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10	-1.27 Seizures per week Standard Deviation 3.567	1.41 Seizures per week Standard Deviation 15.075

SECONDARY outcome

Timeframe: Baseline and at Week 3 through Week 10

Population: Only those participants with data available during Weeks 3 to 10 were analyzed.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=46 Participants Placebo Suspension 50 mg/mL TID
Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10	-1.07 Seizures per week Standard Deviation 3.909	2.52 Seizures per week Standard Deviation 20.229

SECONDARY outcome

Timeframe: Baseline and at Week 1 through Week 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed

Summary of percent change from Baseline in mean weekly seizure frequency is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 1 Through 10	-17.59 Percent change Standard Deviation 48.867	1.99 Percent change Standard Deviation 63.160

SECONDARY outcome

Timeframe: Baseline and at Week 3 through Week 10

Population: Only those participants with data available during Weeks 3 to 10 were analyzed.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=46 Participants Placebo Suspension 50 mg/mL TID
Percent Change From Baseline in Mean Weekly Seizure Frequency During Weeks 3 Through 10	-12.08 Percent change Standard Deviation 54.286	4.57 Percent change Standard Deviation 71.880

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed

Mean weekly Seizure Frequency for each week post-dosing During Weeks 1 to 10 is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 1	4.53 Seizures per week Standard Deviation 11.195	7.25 Seizures per week Standard Deviation 21.668
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 2	5.09 Seizures per week Standard Deviation 9.638	8.79 Seizures per week Standard Deviation 34.548
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 3	5.02 Seizures per week Standard Deviation 9.743	7.80 Seizures per week Standard Deviation 28.163
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 4	5.69 Seizures per week Standard Deviation 10.738	9.13 Seizures per week Standard Deviation 30.768
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 5	5.12 Seizures per week Standard Deviation 9.085	11.64 Seizures per week Standard Deviation 42.864
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 6	5.65 Seizures per week Standard Deviation 8.894	10.43 Seizures per week Standard Deviation 38.133
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 7	6.68 Seizures per week Standard Deviation 10.894	13.15 Seizures per week Standard Deviation 62.762
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 8	4.63 Seizures per week Standard Deviation 8.401	13.47 Seizures per week Standard Deviation 63.157
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 9	5.07 Seizures per week Standard Deviation 9.897	11.64 Seizures per week Standard Deviation 49.387
Mean Weekly Seizure Frequency for Each Week After Dosing During Weeks 1 to 10 Week 10	4.83 Seizures per week Standard Deviation 9.282	13.60 Seizures per week Standard Deviation 56.711

SECONDARY outcome

Timeframe: Baseline and at Week 1 through Week 10

Population: Only those participants with data available during Weeks 1 to 10 were analyzed.

Seizure subtypes included Complex partial seizures (CPS), Generalized tonic-clonic seizure (GTCS), and Simple partial seizure (SPS)-motor. Percent Change from Baseline in Mean Weekly Seizure frequency by seizure subtype is presented. Baseline was defined as the Day 0 assessment before study drug infusion. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Outcome measures

Outcome measures
Measure	Ganaxolone n=96 Participants Suspension formulation 50 mg/mL TID	Placebo n=47 Participants Placebo Suspension 50 mg/mL TID
Percent Change From Baseline in Mean Weekly Seizure Frequency by Subtype During Weeks 1 Through 10 CPS	-17.47 Percent change Standard Error 51.055	3.88 Percent change Standard Error 82.986
Percent Change From Baseline in Mean Weekly Seizure Frequency by Subtype During Weeks 1 Through 10 GTC	-30.65 Percent change Standard Error 79.104	-37.75 Percent change Standard Error 64.091
Percent Change From Baseline in Mean Weekly Seizure Frequency by Subtype During Weeks 1 Through 10 SPS-motor	-30.63 Percent change Standard Error 81.214	19.70 Percent change Standard Error 195.966

SECONDARY outcome

Timeframe: Baseline and at Week 1 through Week 10

Population: ITT Population.

Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=49 Participants Placebo Suspension 50 mg/mL TID
Number of Responders During Weeks 1 Through 10	23 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline and at Week 3 through Week 10

Population: ITT Population.

Responders were defined as participants experiencing ≥50% of reduction in mean weekly seizure frequency from the Baseline. Baseline was defined as the Day 0 assessment before study drug infusion.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=49 Participants Placebo Suspension 50 mg/mL TID
Number of Responders During Weeks 3 Through 10	25 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to Week 2

Population: Only those participants with data available Up to week 2 were analyzed.

Number of seizure-free participants is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Participants Up to Week 2	16 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 3 through Week 10

Population: Only those participants with data available during Weeks 3 to 10 were analyzed.

Number of seizure-free participants is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=46 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Participants During Weeks 3 Through 10	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 1 through Week 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed

Number of seizure-free participants is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Participants During Weeks 1 Through 10	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 2

Population: Only those participants with data available up to Week 2 were analyzed.

Summary of Seizure-Free days is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Days Up to Week 2	10.3 Seizure free days Standard Deviation 4.41	10.0 Seizure free days Standard Deviation 3.78

SECONDARY outcome

Timeframe: Week 3 through Week 10

Population: Only those participants with data available during Weeks 3 to 10 were analyzed.

Summary of Seizure-Free days is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=95 Participants Suspension formulation 50 mg/mL TID	Placebo n=46 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Days During Week 3 Through 10	37.1 Seizure free days Standard Deviation 18.50	38.5 Seizure free days Standard Deviation 16.17

SECONDARY outcome

Timeframe: Week 1 through Week 10

Population: ITT Population. Only those participants with data available at the specified data points were analyzed

Summary of Seizure-Free days is presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=98 Participants Suspension formulation 50 mg/mL TID	Placebo n=48 Participants Placebo Suspension 50 mg/mL TID
Number of Seizure-free Days During Week 1 Through 10	45.9 Seizure free days Standard Deviation 22.11	46.8 Seizure free days Standard Deviation 20.59

Adverse Events

Ganaxolone

Serious events: 5 serious events

Other events: 82 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Marinus

Marinus Pharmaceuticals, Inc.

Phone: (484) 801-4670

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Ganaxolone n=98 participants at risk Suspension formulation 50 mg/mL TID	Placebo n=49 participants at risk Placebo Suspension 50 mg/mL TID
Injury, poisoning and procedural complications Brain contusion	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Burns second degree	0.00% 0/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	2.0% 1/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Hemothorax	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Subdural hematoma	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	2.0% 1/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	0.00% 0/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	2.0% 1/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Enteritis	0.00% 0/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	2.0% 1/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Epilepsy	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Migraine	0.00% 0/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	2.0% 1/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Postictal state	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Investigations Hematocrit decreased	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Hemaglobin decreased	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Mediastinal shift	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary hematoma	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	1.0% 1/98 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.	0.00% 0/49 • Screening through Week 14 Adverse events (AEs) and Serious adverse events (SAEs) were collected for ITT Population which consisted of all randomized participants who received at least 1 dose of study medication.