Trial Outcomes & Findings for A Two-year Open-label Extension Study of Ganaxolone in Patients With Drug-resistant Partial-onset Seizures (NCT NCT02519439)
NCT ID: NCT02519439
Last Updated: 2023-06-28
Results Overview
Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period of Study 1042-0603 (less than or equal to 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Post-baseline 28-day seizure frequency was calculated as the number of seizures in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Baseline was defined as the last non-missing value obtained before the first treatment in the preceding Study 1042-0603. The calculation for percent change from Baseline in 28-day seizure frequency was done as follows for each participant: post-Baseline 28-day seizure frequency minus Baseline 28-day seizure frequency whole divided by Baseline 28-day seizure frequency multiplied by 100 percent.
TERMINATED
PHASE3
26 participants
Baseline and at Day 28
2023-06-28
Participant Flow
This was an open-label extension of Study 1042-0603, providing a two-year adjunctive ganaxolone treatment to adult participants with epilepsy consisting of partial-onset seizures (POS).
A total of 26 participants moved in from 1042-0603 (NCT01963208) study. As Ganaxolone missed its primary endpoint in the double-blind portion of the 1042-0603 study, the study was terminated.
Participant milestones
| Measure |
Ganaxolone
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Overall Study
STARTED
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26
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Overall Study
COMPLETED
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5
|
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Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Ganaxolone
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
|
Overall Study
Study Termination
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19
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Overall Study
Withdrawal by Subject
|
1
|
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Overall Study
Adverse Event
|
1
|
Baseline Characteristics
A Two-year Open-label Extension Study of Ganaxolone in Patients With Drug-resistant Partial-onset Seizures
Baseline characteristics by cohort
| Measure |
Ganaxolone
n=26 Participants
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Age, Continuous
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44.3 Years
STANDARD_DEVIATION 15.03 • n=5 Participants
|
|
Sex: Female, Male
Female
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11 Participants
n=5 Participants
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Sex: Female, Male
Male
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15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
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3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and at Day 28Population: Full Analysis Population included participants who returned at least 25 days of seizure calendar data.
Baseline 28-day seizure frequency was calculated as the number of seizures in the Baseline period of Study 1042-0603 (less than or equal to 56 days) divided by the number of days with available seizure data in the Baseline period and multiplied by 28. Post-baseline 28-day seizure frequency was calculated as the number of seizures in the entire treatment period divided by the number of days with available seizure data in the treatment period and multiplied by 28. Baseline was defined as the last non-missing value obtained before the first treatment in the preceding Study 1042-0603. The calculation for percent change from Baseline in 28-day seizure frequency was done as follows for each participant: post-Baseline 28-day seizure frequency minus Baseline 28-day seizure frequency whole divided by Baseline 28-day seizure frequency multiplied by 100 percent.
Outcome measures
| Measure |
Ganaxolone
n=26 Participants
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Percent Change From Baseline in 28-day Seizure Frequency
|
-41.86 Percent change
Standard Deviation 44.913
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SECONDARY outcome
Timeframe: Baseline and at Day 28Population: Full Analysis Population.
A 50% responder is an individual whose reduction of percent change from Baseline to the end of the open label extension period in 28-day partial-onset seizure (POS) seizure frequency is greater than or equal to 50%.
Outcome measures
| Measure |
Ganaxolone
n=26 Participants
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Number of Participants Who Showed Greater Than or Equal to 50% Reduction in 28-day Seizure Frequent From Baseline
|
14 Participants
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SECONDARY outcome
Timeframe: At Week 104Population: Safety Population included all participants who signed informed consent and took one dose of study medication in this study. Only those participants with data available at indicated timepoints has been presented.
The CGI-I scale is a clinician-rated 7-point scale used to assess how much the participant's illness had improved or worsened relative to a Baseline state at the beginning of the intervention. It was rated as: 1. "very much improved" 2. "much improved" 3. "minimally improved" 4. "no change" 5. "minimally worse" 6. "much worse" 7. "very much worse". Higher scores indicated worse condition. Participants who showed CGI improvement at Week 104 (End of treatment) has been presented.
Outcome measures
| Measure |
Ganaxolone
n=23 Participants
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
|
|---|---|
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Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Very much improved
|
1 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Much improved
|
9 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Minimally improved
|
11 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
No change
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2 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Minimally worse
|
0 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Much worse
|
0 Participants
|
|
Number of Participants With Clinical Global Impression of Improvement (CGI-I) Scores
Very much worse
|
0 Participants
|
SECONDARY outcome
Timeframe: At Week 104Population: Safety Population. Only those participants with data available at indicated time points has been presented.
The participant is asked to rate the total improvement of their partial-onset seizures whether or not in the participant's judgment it is due entirely to drug treatment based on a 7-point scale using the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse, or very much worse" (1 = very much improved; 7 = very much worse). Higher scores indicated worse condition. Participants who showed PGI improvement at Week 104 (End of treatment) has been presented.
Outcome measures
| Measure |
Ganaxolone
n=23 Participants
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Very much improved
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4 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Much improved
|
8 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Minimally improved
|
10 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
No change
|
1 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Minimally worse
|
0 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Much worse
|
0 Participants
|
|
Number of Participants With Patient/Caregiver Global Impression of Improvement (PGI-I) Scores
Very much worse
|
0 Participants
|
Adverse Events
Ganaxolone
Serious adverse events
| Measure |
Ganaxolone
n=26 participants at risk
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Respiratory, thoracic and mediastinal disorders
Pulmonary embolism/
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
Other adverse events
| Measure |
Ganaxolone
n=26 participants at risk
Participants entered the study at their current dose of ganaxolone (450 milligrams \[mg\] to 900 mg twice daily; up to a maximum dose of 1800 mg per day) from Study 1042-0603 (NCT01963208). The dose of ganaxolone has been adjusted for tolerability and response.
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|---|---|
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Nervous system disorders
Headache
|
11.5%
3/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Nervous system disorders
Dizziness
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Nervous system disorders
Syncope
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Infections and infestations
Cellulitis
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Infections and infestations
Tooth infection
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Injury, poisoning and procedural complications
Fall
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Injury, poisoning and procedural complications
Lip injury
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Eye disorders
Lacrimal disorder
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Eye disorders
Vision blurred
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Gastrointestinal disorders
Nausea
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
General disorders
Pyrexia
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Investigations
Hepatic enzyme increased
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Psychiatric disorders
Insomnia
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Renal and urinary disorders
Calculus ureteric
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
|
Vascular disorders
Hypertension
|
3.8%
1/26 • Up to Week 104
Adverse events and Serious adverse events were collected in Safety Population.
|
Additional Information
Marinus Clinical Trials Submission Manager
Marinus Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place