Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01529034
• Collaborator: (none)
• Enrollment: 175
• Locations: 58
• Arm: 1
• Patients Per Site: 3

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: USL261	Phase 3

Detailed Description

Participants who completed study P261-401 (NCT01390220), a randomized double-blind study of USL261 (intranasal midazolam) versus placebo to acutely treat a seizure cluster episode, were eligible to to enroll in this open-label extension study (P261-402). The participant's caregiver administered a USL261 5 milligram (mg) dose for a seizure episode meeting study criteria. A second USL261 5 mg dose could be administered after 10 minutes and up to 6 hours after the first dose for persistent or recurrent seizures, unless the participant met exclusions to administration of the second dose. A participant could have more than 1 seizure cluster episode treated during his/her study participation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 175 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
• Actual Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: USL261 Intranasal midazolam 5 mg	Drug: USL261

Outcome Measures

Primary Outcome Measures

1. Duration of Safety Observation [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Duration of participant study participation for collection of long term safety data

2. Participants Meeting Predefined Safety Criteria for Vital Signs [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants meeting predefined safety criteria for vital signs (systolic blood pressure [SBP] <85 mm Hg, SBP change from baseline >/= 40 mm Hg, diastolic BP [DBP] <50 mm Hg, DBP change from baseline >/=30 mm Hg, pulse rate <50 beats per minute (bpm), pulse rate >120 bpm, pulse rate change >/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate [RR] <8 breaths per minute (brpm) or >24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.

3. Participants With Laboratory Abnormalities Meeting Predefined Criteria [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)

4. Participants With Clinically Significant Abnormalities Physical Examination [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.

5. Participants With Clinically Significant Abnormalities on Neurologic Examination [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator

6. Participants With Clinically Significant Abnormalities on Nasal Examination [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator

7. Participant Change in B-SIT Score [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.

8. Participants With Suicidal Ideation [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.

9. Emergency Room/Emergency Medical Service Visits [From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.]

   Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)

Secondary Outcome Measures

1. Number of Treated Seizure Clusters Meeting Criteria for Treatment Success [6 hours after first dose of USL261 for each treated seizure cluster]

   Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes

• Has successfully completed study P261-401, and the subject and caregiver have demonstrated adequate compliance with P261-401 study procedures as determined by the investigator

Exclusion Criteria:

• Has experienced status epilepticus during or since the P261-401 study

• In the opinion of the investigator, is experiencing an ongoing, uncontrolled, clinically significant adverse event(s) from P261-401 at Visit 1 or did experience a clinically significant adverse event in study P261-401 that might prevent the subject from safely participating in the study

• Has a neurological disorder that is likely to progress in the next year

• Has a history of acute narrow-angle glaucoma

• Has a medical condition including uncontrolled cardiac, pulmonary, renal, hepatic, or gastrointestinal disease that could interfere with the study, subject safety/safety monitoring, or is not stable despite current therapy

• Subject has severe chronic cardio-respiratory disease or the need for ambulatory oxygen

• Has had psychogenic, non-epileptic seizure(s) during or since the P261-401 study

• Has active suicidal plan or intent as determined by the C-SSRS at Visit 1 or medical history

• Subject has had vagus nerve stimulator (VNS) implanted since the completion of study P261-401

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	United States, Arizona	Phoenix	Arizona	United States
2	United States, Arizona	Scottsdale	Arizona	United States
3	United States, Arizona	Tucson	Arizona	United States
4	United States, Arkansas	Little Rock	Arkansas	United States
5	United States, California	Fresno	California	United States
6	United States, California	Sacramento	California	United States
7	United States, California	Ventura	California	United States
8	United States, Colorado	Aurora	Colorado	United States
9	United States, Connecticut	New Haven	Connecticut	United States
10	United States, Florida	Port Charlotte	Florida	United States
11	United States, Florida	Wellington	Florida	United States
12	United States, Idaho	Boise	Idaho	United States
13	United States, Illinois	Chicago	Illinois	United States
14	United States, Kentucky	Lexington	Kentucky	United States
15	United States, Maryland	Baltimore	Maryland	United States
16	United States, Michigan	Detroit	Michigan	United States
17	United States, Minnesota	Saint Paul	Minnesota	United States
18	United States, Missouri	Saint Louis	Missouri	United States
19	United States, New Hampshire	Lebanon	New Hampshire	United States
20	United States, New Jersey	Hackensack	New Jersey	United States
21	United States, New York	Bronx	New York	United States
22	United States, New York	New York	New York	United States
23	United States, New York	Stony Brook	New York	United States
24	United States, North Carolina	Durham	North Carolina	United States
25	United States, North Carolina	Winston-Salem	North Carolina	United States
26	United States, Oklahoma	Oklahoma City	Oklahoma	United States
27	United States, Pennsylvania	Philadelphia	Pennsylvania	United States
28	United States, Tennessee	Memphis	Tennessee	United States
29	United States, Tennessee	Nashville	Tennessee	United States
30	United States, Texas	Dallas	Texas	United States
31	United States, Texas	Greenville	Texas	United States
32	Australia, New South Wales	Randwick	New South Wales	Australia
33	Australia, Victoria	Heidelberg west	Victoria	Australia
34	Australia, Victoria	Parkville	Victoria	Australia
35	Canada	Montreal	Ontario	Canada
36	Canada, Toronto	Toronto	Ontario	Canada
37	Canada	Toronto	Quebec	Canada
38	Germany	Munchen	Bayern	Germany
39	Germany	Marberg	Hessen	Germany
40	Germany	Bonn	Nordrhein-Westfalen	Germany
41	Germany	Bielefeld	Westfalen-Lippe	Germany
42	Hungary	Budapest		Hungary
43	Israel	Haifa		Israel
44	Israel	Petah Tikvah		Israel
45	Israel	Ramat Gan		Israel
46	New Zealand	Christchurch	Canterbury	New Zealand
47	Poland	Gdansk		Poland
48	Poland	Katowice		Poland
49	Poland	Lublin		Poland
50	Spain	Sevilla	Andalucia	Spain
51	Spain	Gerona	Cataluyna	Spain
52	Spain	Madrid		Spain
53	Ukraine	Ivano-Frankivsk		Ukraine
54	Ukraine	Kharkiv		Ukraine
55	Ukraine	Odessa		Ukraine
56	Ukraine	Poltava		Ukraine
57	Ukraine	Ternopil		Ukraine
58	Ukraine	Vinnytsa		Ukraine

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 20, 2015
• Statistical Analysis Plan - May 15, 2017

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT01529034
• Other Study ID Numbers: P261-402; 2011-004109-25
• First Posted: Feb 8, 2012
• Last Update Posted: Oct 18, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by UCB Biopharma S.P.R.L.: Epilepsy; seizure clusters; acute repetitive seizures; rescue treatment
• Additional relevant MeSH terms: Epilepsy; Seizures

Study Results

Participant Flow

Pre-assignment Detail	The participant flow refers to the enrolled population and includes participants who did not treat a seizure cluster episode.

Arm/Group Title	USL261
Arm/Group Description	5 mg intranasal midazolam USL261
Period Title: Overall Study
STARTED	175
Exposed	161
COMPLETED	1
NOT COMPLETED	174

Baseline Characteristics

Arm/Group Title	USL261
Arm/Group Description	5 mg intranasal midazolam USL261
Overall Participants	161
Age (Count of Participants)
<=18 years	8 5%
Between 18 and 65 years	153 95%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.9 (11.96)
Sex: Female, Male (Count of Participants)
Female	80 49.7%
Male	81 50.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 5%
Not Hispanic or Latino	153 95%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.2%
Asian	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 2.5%
White	152 94.4%
More than one race	0 0%
Unknown or Not Reported	2 1.2%
Region of Enrollment (participants) [Number]
Canada	1 0.6%
Hungary	10 6.2%
United States	56 34.8%
Ukraine	53 32.9%
Poland	12 7.5%
Israel	5 3.1%
Australia	12 7.5%
Germany	7 4.3%
Spain	5 3.1%
Body Mass Index (kg/m˄2) [Median (Full Range) ]
Median (Full Range) [kg/m˄2]	24.7
Seizure cluster episodes in year before Visit 1 in Study P261-401 (seizure cluster episodes) [Median (Full Range) ]
Median (Full Range) [seizure cluster episodes]	18.0
Years had seizure cluster episodes prior to Study P261-401 (years) [Median (Full Range) ]
Median (Full Range) [years]	5.00
Typical number of seizures in seizure cluster episode (seizures) [Median (Full Range) ]
Median (Full Range) [seizures]	6.0
Typical duration of seizure cluster episode (hours) [Median (Full Range) ]
Median (Full Range) [hours]	1.00

Outcome Measures

1. Primary Outcome

Title	Duration of Safety Observation
Description	Duration of participant study participation for collection of long term safety data
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5mg on study

Arm/Group Title	USL261
Arm/Group Description	5 mg intranasal midazolam USL261
Measure Participants	161
Median (Full Range) [months]	16.80

2. Primary Outcome

Title	Participants Meeting Predefined Safety Criteria for Vital Signs
Description	Participants meeting predefined safety criteria for vital signs (systolic blood pressure [SBP] <85 mm Hg, SBP change from baseline >/= 40 mm Hg, diastolic BP [DBP] <50 mm Hg, DBP change from baseline >/=30 mm Hg, pulse rate <50 beats per minute (bpm), pulse rate >120 bpm, pulse rate change >/= 40 bpm at any visit post baseline or for caregiver recorded participant respiration rate [RR] <8 breaths per minute (brpm) or >24 brpm) after any USL261 treated seizure cluster episode. Abnormal vital signs were assessed separately by investigator and recorded as adverse events if applicable.
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
SBP <85 mm Hg	0 0%
SBP change from baseline ≥ 40 mm Hg	1 0.6%
DBP <50 mm Hg	2 1.2%
DBP change from baseline ≥ 30 mm Hg	3 1.9%
Pulse rate <50 bpm	2 1.2%
Pulse rate >120 bpm	1 0.6%
Pulse rate change from baseline >/= 40 bpm	4 2.5%
Caregiver recorded RR <8 brpm	1 0.6%
Caregiver recorded RR >24 brpm	29 18%

3. Primary Outcome

Title	Participants With Laboratory Abnormalities Meeting Predefined Criteria
Description	Participants with abnormal laboratory finding, at any time post baseline, meeting predefined criteria. Abnormal laboratory findings were assessed separately by investigator and recorded as adverse events if applicable. Alanine aminotransferase (ALT); Alkaline phosphatase (ALP); Aspartate aminotransferase (AST); Gamma glutamyl transferase (GGT); upper limit of normal (ULN)
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
ALT >ULN & ≤3xULN	26 16.1%
Albumin <30 g/L	2 1.2%
ALP >2.5xULN	1 0.6%
AST >ULN & ≤3xULN	17 10.6%
AST >5x ULN & <20xULN	1 0.6%
Bicarbonate <15.9 mmol/L	6 3.7%
Cholesterol >7.75 mmol/L	5 3.1%
Creatinine >1.5xULN	1 0.6%
Creatinine >2x baseline	2 1.2%
GGT >2.5xULN	14 8.7%
Glucose <3 mmol/L	3 1.9%
Glucose <8.9 mmol/L	5 3.1%
Phosphate <0.8 mmol/L	13 8.1%
Potassium >5.5 mmol/L	5 3.1%
Sodium <130 mmol/L	11 6.8%
Sodium >150 mmol/L	1 0.6%
Hemoglobin <100 g/L	5 3.1%
Hemoglobin decrease 20 g/L	10 6.2%
Leukocytes <3x10^9/L	4 2.5%
Lymphocytes <0.8x10^9/L	4 2.5%
Neutrophils <1.5x10^9/L	8 5%

4. Primary Outcome

Title	Participants With Clinically Significant Abnormalities Physical Examination
Description	Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
Skin	2 1.2%
Head/Eyes/Ears/Nose/Throat	0 0%
Neck	1 0.6%
Thyroid	0 0%
Lungs	0 0%
Heart	0 0%
Abdomen	0 0%
Lymph nodes	0 0%
Extremities	0 0%

5. Primary Outcome

Title	Participants With Clinically Significant Abnormalities on Neurologic Examination
Description	Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
Mental status	10 6.2%
Cranial nerves II-XII	1 0.6%
Motor strength of limbs	2 1.2%
Deep tendon reflexes	2 1.2%
Sensory exam	1 0.6%
Station and gait	5 3.1%
Hopping	0 0%
Romberg test	0 0%
Finger-to-nose test	1 0.6%
Heel-to-shin test	1 0.6%
Rapid alternating movements	2 1.2%
Nystagmus	0 0%
Tremor/Other abnormal movements	0 0%

6. Primary Outcome

Title	Participants With Clinically Significant Abnormalities on Nasal Examination
Description	Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
Count of Participants [Participants]	1 0.6%

7. Primary Outcome

Title	Participant Change in B-SIT Score
Description	Change in participant Brief Smell Identification Test (B-SIT) score from baseline to last visit with assessment. The B-SIT is a self-administered 12-item test; the score indicates odors correctly identified (0 to 12). The B-SIT was added while the study was already ongoing (Protocol Amendment 4, 20 May 2015) in response to a regulatory request. The test was only implemented at sites in the United States and included only participants considered by the investigator to have adequate cognitive ability to perform the test. Baseline was defined as the latest non-missing value prior to administration of USL261 in the Test Dose Phase of Study P261-401.
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study, had a baseline B-SIT in Study P261-401, and a post-baseline B-SIT in Study P261-402.

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	9
Mean (Standard Deviation) [score on a scale]	-0.6 (1.2)

8. Primary Outcome

Title	Participants With Suicidal Ideation
Description	Participants with suicidal ideation reported on Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at any post-baseline visit. Responses including: Wish to be Dead; Non-Specific Active Suicidal Thoughts; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent; and Any Suicidal Ideation Regardless of Type.
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
Wish to be dead	3 1.9%
Non-specific active	3 1.9%
Active without specific plan	3 1.9%
Active with specific plan/intent	1 0.6%
Any suicidal ideation	4 2.5%

9. Primary Outcome

Title	Emergency Room/Emergency Medical Service Visits
Description	Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
Time Frame	From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of USL261 5 mg on study

Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
Measure Participants	161
Count of Participants [Participants]	20 12.4%

10. Secondary Outcome

Title	Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
Description	Number of Treated Seizure Clusters Meeting Criteria for Treatment Success: Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after administration of first dose of USL261 (intranasal midazolam 5 mg)
Time Frame	6 hours after first dose of USL261 for each treated seizure cluster

Outcome Measure Data

Analysis Population Description

Seizure cluster episodes treated with first dose of USL261

Arm/Group Title	USL261
Arm/Group Description	5 mg intranasal midazolam USL261
Measure Participants	161
Measure Seizure cluster episodes	1998
Count of Units [Seizure cluster episodes]	1108

Adverse Events

Time Frame	Original protocol - each participant 2 years from enrollment; Amended protocol - each participant open-ended from enrollment (up to 4 years or longer as approved by Health Authority where study being conducted). Actual individual participant duration 1.0 to 55.7 months.
Adverse Event Reporting Description	Adverse events collected at each visit from participant and/or caregiver. Due to intermittent treatment (qualifying seizure clusters), short systemic half-life of active (midazolam), and long participant duration, treatment emergent adverse event within 2 days after each treated seizure cluster are reported. Seizures were not considered adverse events unless worsening from underlying condition.
Arm/Group Title	USL261
Arm/Group Description	USL261 5 mg or USL261 5 mg + 5 mg for a treated seizure cluster episode
All Cause Mortality
	USL261
	Affected / at Risk (%)	# Events
Total	0/161 (0%)
Serious Adverse Events
	USL261
	Affected / at Risk (%)	# Events
Total	8/161 (5%)
Gastrointestinal disorders
Nausea	1/161 (0.6%)	1
General disorders
Pyrexia	1/161 (0.6%)	1
Investigations
Blood pressure increased	1/161 (0.6%)	1
Nervous system disorders
Seizure cluster	2/161 (1.2%)	4
Convulsion	2/161 (1.2%)	3
Status epilepticus	2/161 (1.2%)	2
Epilepsy	1/161 (0.6%)	1
Other (Not Including Serious) Adverse Events
	USL261
	Affected / at Risk (%)	# Events
Total	33/161 (20.5%)
Nervous system disorders
Somnolence	15/161 (9.3%)	92
Headache	10/161 (6.2%)	27
Respiratory, thoracic and mediastinal disorders
Nasal discomfort	20/161 (12.4%)	96

Limitations/Caveats

Open-label, non-comparative design. Potential participation bias due to participants and/or caregiver perceived efficacy/safety in prior study. Seizure data capture in diaries diminished over time in some participants due to length of study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A manuscript or abstract should not be submitted by investigator(s) for publication or presentation until a New Drug Application is approved by the US FDA or permission is granted in writing by sponsor.