Trial Outcomes & Findings for Study to Evaluate the Safety and Efficacy of USL261 in Patients With Increased Bouts of Seizure Activity in the EMU (NCT NCT01999777)

NCT ID: NCT01999777

Last Updated: 2019-10-10

Results Overview

A participant was considered "seizure-free" if he or she completed the 6-hour Treatment Phase without seizures recorded, premature discontinuation of study drug, rescue intervention for acute central respiratory depression adverse event (AE), and alterations to background anti-epileptic drug (AED) therapy. Otherwise, the participant was included in the analysis for seizure-free events with the outcome of "seizure."

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

62 participants

Primary outcome timeframe

6 hours

Results posted on

2019-10-10

Participant Flow

188 eligible subjects entered Pretreatment Observation during which they were monitored in EMU for seizure events. Only subjects who met entry criteria and presented with seizure events meeting the treatment decision criteria were eligible to enter the Treatment Phase. Participant flow represents subjects who took at least 1 dose of study drug.

Participant milestones

Participant milestones
Measure	USL261 5 mg intranasal midazolam USL261	Placebo intranasal placebo Placebo
Overall Study STARTED	31	31
Overall Study COMPLETED	31	31
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Safety and Efficacy of USL261 in Patients With Increased Bouts of Seizure Activity in the EMU

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	USL261 n=31 Participants 5 mg intranasal midazolam USL261	Placebo n=31 Participants intranasal placebo Placebo	Total n=62 Participants Total of all reporting groups
Age, Categorical <=18 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	32.7 years STANDARD_DEVIATION 12.94 • n=5 Participants	35.9 years STANDARD_DEVIATION 13.56 • n=7 Participants	34.3 years STANDARD_DEVIATION 13.24 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants	29 Participants n=7 Participants	57 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	0 Participants n=5 Participants	1 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	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	27 Participants n=7 Participants	53 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	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	44 participants n=5 Participants
Region of Enrollment Czechia	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Lithuania	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Germany	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Spain	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 hours

Population: Intent to treat

Outcome measures

Outcome measures
Measure	USL261 n=31 Participants 5 mg intranasal midazolam USL261	Placebo n=31 Participants intranasal placebo Placebo
Number of Participants That Were Seizure-free	17 Participants	12 Participants

SECONDARY outcome

Timeframe: 6 hours

Population: Intent-to-treat

Time to first seizure following treatment was defined as time from treatment with study drug to the onset of the next seizure, rescue intervention (for acute central respiratory depression AE) to maintain subject safety, alterations to background AED therapy, early termination, or 6 hours, whichever came first.

Outcome measures

Outcome measures
Measure	USL261 n=31 Participants 5 mg intranasal midazolam USL261	Placebo n=31 Participants intranasal placebo Placebo
Time to First Seizure Following Treatment (TFSFT)	NA hours Interval 4.0 to Unable to estimate median as \> 50% were seizure-free throughout the 6-hour treatment phase. No upper CI boundary as observations stopped at 6 hours.	3.9 hours Interval 1.8 to No upper CI boundary as observations stopped at 6 hours.

Adverse Events

USL261

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	USL261 n=31 participants at risk 5 mg intranasal midazolam USL261	Placebo n=31 participants at risk intranasal placebo Placebo
Gastrointestinal disorders Nausea	9.7% 3/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	3.2% 1/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
General disorders Product taste abnormal	6.5% 2/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	19.4% 6/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Infections and infestations Rhinitis	0.00% 0/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	6.5% 2/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Injury, poisoning and procedural complications Tongue injury	0.00% 0/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	6.5% 2/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Nervous system disorders Headache	3.2% 1/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	16.1% 5/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Nervous system disorders Somnolence	6.5% 2/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	0.00% 0/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	16.1% 5/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	16.1% 5/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.
Respiratory, thoracic and mediastinal disorders Throat irritation	9.7% 3/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.	9.7% 3/31 • From informed consent until up to 48 hours of completion of the Treatment Phase Adverse events were collected from time of informed consent until subject completion or early termination. Exit assessments were to be conducted within 48 hours of completion of the Treatment Phase (6 hours) and prior to discharge for the EMU.

Additional Information

David Sequeira,

Proximagen, LLC

Phone: 952-658-7437

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 the sponsor.
Publication restrictions are in place

Restriction type: OTHER