Trial Outcomes & Findings for Evaluation of Efficacy and Safety of OXC XR as Adjunctive Therapy for Partial Seizures (NCT NCT00772603)

Last Updated: 2014-02-11

Results Overview

Percent change (PCH) in seizure frequency per 28d relative to Baseline, Treatment Phase (PCH\[T\]), Intent-to-Treat population.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

366 participants

Primary outcome timeframe

Change at 16 weeks (4wks Titration + 12 wks Maintenance) compared to Baseline

Results posted on

2014-02-11

Participant Flow

Adult patients with refractory partial onset epilepsy were recruited from December 2009 to March 2011 at clinical sites in 8 countries.

Patients had at least three partial seizures per 28 days during an 8 week Baseline Period. Subjects were receiving treatment with one to three antiepileptic drugs and were on stable treatment for a minimum of 4 weeks. Subjects with a diagnosis other than partial epilepsy were excluded.

Participant milestones

Participant milestones
Measure	2400mg/Day SPN-804 2400mg of SPN-804O once daily	1200mg/Day SPN-804 1200mg SPN-804O once daily	Placebo Placebo once daily
Overall Study STARTED	123	122	121
Overall Study COMPLETED	71	82	95
Overall Study NOT COMPLETED	52	40	26

Reasons for withdrawal

Reasons for withdrawal
Measure	2400mg/Day SPN-804 2400mg of SPN-804O once daily	1200mg/Day SPN-804 1200mg SPN-804O once daily	Placebo Placebo once daily
Overall Study Withdrawal by Subject	11	10	6
Overall Study Adverse Event	37	18	10
Overall Study Subject Non-compliance	1	6	4
Overall Study Protocol Violation	0	1	1
Overall Study Lost to Follow-up	1	5	2
Overall Study Physician Decision	0	0	1
Overall Study Other	2	0	2

Baseline Characteristics

Evaluation of Efficacy and Safety of OXC XR as Adjunctive Therapy for Partial Seizures

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2400mg/Day SPN-804 n=123 Participants 2400mg SPN-804O once daily	1200mg/Day SPN-804 n=122 Participants 1200mg SPN-804O given once daily	Placebo n=121 Participants Placebo given once daily.	Total n=366 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	123 Participants n=5 Participants	122 Participants n=7 Participants	121 Participants n=5 Participants	366 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	38.5 years STANDARD_DEVIATION 11.58 • n=5 Participants	39.1 years STANDARD_DEVIATION 11.51 • n=7 Participants	39.1 years STANDARD_DEVIATION 12.49 • n=5 Participants	38.9 years STANDARD_DEVIATION 11.84 • n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	71 Participants n=7 Participants	67 Participants n=5 Participants	202 Participants n=4 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	51 Participants n=7 Participants	54 Participants n=5 Participants	164 Participants n=4 Participants
Region of Enrollment United States	20 participants n=5 Participants	23 participants n=7 Participants	26 participants n=5 Participants	69 participants n=4 Participants
Region of Enrollment Mexico	15 participants n=5 Participants	16 participants n=7 Participants	14 participants n=5 Participants	45 participants n=4 Participants
Region of Enrollment Canada	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Region of Enrollment Poland	25 participants n=5 Participants	16 participants n=7 Participants	13 participants n=5 Participants	54 participants n=4 Participants
Region of Enrollment Romania	8 participants n=5 Participants	10 participants n=7 Participants	6 participants n=5 Participants	24 participants n=4 Participants
Region of Enrollment Croatia	10 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants	29 participants n=4 Participants
Region of Enrollment Russian Federation	28 participants n=5 Participants	31 participants n=7 Participants	31 participants n=5 Participants	90 participants n=4 Participants
Region of Enrollment Bulgaria	17 participants n=5 Participants	18 participants n=7 Participants	18 participants n=5 Participants	53 participants n=4 Participants

PRIMARY outcome

Timeframe: Change at 16 weeks (4wks Titration + 12 wks Maintenance) compared to Baseline

Population: All safety population subjects with baseline Seizure Diary data and at least one visit during the Treatment Phase (ITT population). Subjects must have had at least 3 consecutive weeks of Seizure Diary data (SDD) in the Baseline Phase and at least 14 consecutive days of SDD after starting study drug.

Percent change (PCH) in seizure frequency per 28d relative to Baseline, Treatment Phase (PCH\[T\]), Intent-to-Treat population.

Outcome measures

Outcome measures
Measure	2400mg/Day SPN-804 n=111 Participants 2400mg SPN-804 once daily	1200mg/Day SPN-804 n=109 Participants 1200mg SPN-804 once daily	Placebo n=117 Participants Placebo once daily.
PCH(T), ITT	-42.90 percentage of change Full Range 53.11 • Interval -100.0 to 212.8	-38.20 percentage of change Full Range 69.84 • Interval -100.0 to 556.1	-28.70 percentage of change Full Range 67.34 • Interval -100.0 to 333.6

SECONDARY outcome

Timeframe: Change at 12 weeks (Maintenance Period) compared to Baseline

Population: All safety population subjects with adequate baseline Seizure Diary data (at least three consecutive weeks) and at least one visit during the Titration Period and one visit during the Maintenance Period.

Percent change in seizure frequency per 28 days relative to Baseline, Maintenance Period (PCH\[M\]), Intent-to-Treat population

Outcome measures

Outcome measures
Measure	2400mg/Day SPN-804 n=88 Participants 2400mg SPN-804 once daily	1200mg/Day SPN-804 n=97 Participants 1200mg SPN-804 once daily	Placebo n=109 Participants Placebo once daily.
PCH(M)- ITT	-49.15 percentage of change Interval -100.0 to 158.0	-35.30 percentage of change Interval -100.0 to 690.5	-32.90 percentage of change Interval -100.0 to 212.6

SECONDARY outcome

Timeframe: At the end of 16 weeks (4 wks Titration + 12 wks Maintenance)

Percent of patients with a positive response, defined as a 50% or greater reduction in seizure frequency per 28 days relative to Baseline, Treatment Phase, Intent-to-Treat population

Outcome measures

Outcome measures
Measure	2400mg/Day SPN-804 n=109 Participants 2400mg SPN-804 once daily	1200mg/Day SPN-804 n=111 Participants 1200mg SPN-804 once daily	Placebo n=117 Participants Placebo once daily.
Responder Rate, ITT	50 percentage of patients	44 percentage of patients	34 percentage of patients

SECONDARY outcome

Timeframe: At the end of 16 weeks (4 wks Titration + 12 wks Maintenance)

Percent of patients seizure-free during Treatment Phase, Intent-to-Treat population

Outcome measures

Outcome measures
Measure	2400mg/Day SPN-804 n=111 Participants 2400mg SPN-804 once daily	1200mg/Day SPN-804 n=109 Participants 1200mg SPN-804 once daily	Placebo n=117 Participants Placebo once daily.
Seizure-Free Rates, ITT	14 percentage of patients	6 percentage of patients	4 percentage of patients

SECONDARY outcome

Timeframe: At the end of 12 weeks (Maintenance Period)

Percent of patients seizure-free during Maintenance, Intent-to-Treat population

Outcome measures

Outcome measures
Measure	2400mg/Day SPN-804 n=88 Participants 2400mg SPN-804 once daily	1200mg/Day SPN-804 n=97 Participants 1200mg SPN-804 once daily	Placebo n=109 Participants Placebo once daily.
Seizure Free Rate, ITT, (M)	17 percentage of patients	4 percentage of patients	7 percentage of patients

Adverse Events

2400mg/Day SPN-804

Serious events: 10 serious events

Other events: 69 other events

Deaths: 0 deaths

1200mg/Day SPN-804

Serious events: 7 serious events

Other events: 57 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	2400mg/Day SPN-804 n=123 participants at risk 2400mg total daily dose of SPN-804O once a day (QD), given as four 600mg tablets	1200mg/Day SPN-804 n=122 participants at risk 1200mg total daily dose of SPN-804O QD, given as two 600mg tablets and two identical placebo tablets.	Placebo n=121 participants at risk placebo QD, given as four placebo tablets
Nervous system disorders Dizziness	40.7% 50/123 • Number of events 60 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	19.7% 24/122 • Number of events 30 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	14.9% 18/121 • Number of events 21 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Nervous system disorders Somnolence	13.8% 17/123 • Number of events 19 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	11.5% 14/122 • Number of events 14 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	9.1% 11/121 • Number of events 12 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Nervous system disorders Headache	15.4% 19/123 • Number of events 21 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	8.2% 10/122 • Number of events 10 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	7.4% 9/121 • Number of events 12 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Nervous system disorders Balance Disorder	6.5% 8/123 • Number of events 12 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	4.9% 6/122 • Number of events 11 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	5.0% 6/121 • Number of events 7 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Gastrointestinal disorders Vomiting	15.4% 19/123 • Number of events 20 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	5.7% 7/122 • Number of events 10 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	9.1% 11/121 • Number of events 11 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Eye disorders Diplopia	13.0% 16/123 • Number of events 21 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	9.8% 12/122 • Number of events 15 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	4.1% 5/121 • Number of events 5 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
General disorders Asthenia	7.3% 9/123 • Number of events 9 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	3.3% 4/122 • Number of events 4 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	0.83% 1/121 • Number of events 2 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
General disorders Fatigue	3.3% 4/123 • Number of events 5 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	5.7% 7/122 • Number of events 7 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).	0.83% 1/121 • Number of events 1 • All randomized subjects who took at least one dose of study drug. Safety was assessed using adverse events (AEs), clinical laboratory results, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).

Additional Information

Stefan Schwabe, M.D., Ph.D., Chief Medical Officer

Supernus Pharmaceuticals, Inc

Phone: 301-838-2500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER