A Long-term Safety and Tolerability Study of USL261 in Patients With Seizure Clusters

• Sponsor: UCB Biopharma S.P.R.L. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02161185
• Collaborator: (none)
• Enrollment: 7
• Locations: 16
• Arm: 1
• Duration (Months): 12
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 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 Adolescent and Adult Subjects With Seizure Clusters
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: USL261	Drug: USL261; 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol; Other Names: Intranasal Midazolam

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Death, Serious Adverse Events, Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation [Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.]

   Number of Participants with Death, Serious Adverse Events, Treatment emergent adverse events (TEAEs) leading to subject discontinuation from study

Secondary Outcome Measures

1. Treatment Success [Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.]

   Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after study drug administration. Due to early termination of the study, this data was not analyzed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Has a competent, adult caregiver(s) who is able to recognize and observe the subject's seizure cluster episodes

2. Has an established diagnosis of partial or generalized epilepsy that includes all the following:

• A documented history of seizure clusters lasting a minimum of 10 minutes, seizure cluster pattern is observable, stereotyped, and recognizably different from the subject's other non-cluster seizure activity (if any)

• A second seizure in the seizure cluster typically occurs within 6 hours from the time of recognition

• A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures

• A seizure cluster pattern established >3 months before Visit 1

• A frequency of ≥ 3 stereotyped seizure clusters during the year before Visit 1

• At least 1 stereotyped seizure cluster occuring ≤ 4 months before Visit 1

1. Currently on a stable regimen of AED(s) that includes a benzodiazepine

2. Weight is 40 kg to 125 kg, inclusive

Exclusion Criteria:

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

2. Has a severe chronic cardio-respiratory disease

3. Has a psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1

4. Has a history of their stereotypical seizure cluster progressing to status epilepticus within 2 years before Visit 1

5. Has a history of acute narrow-angle glaucoma

6. Has had active suicidal plan/intent or active suicidal thoughts in the 6 months before Visit 1 or a suicide attempt in the past 5 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Tucson	Arizona	United States
2		Fresno	California	United States
3		Ventura	California	United States
4		Aurora	Colorado	United States
5		Port Charlotte	Florida	United States
6		Tampa	Florida	United States
7		Boise	Idaho	United States
8		Chicago	Illinois	United States
9		Lexington	Kentucky	United States
10		Saint Paul	Minnesota	United States
11		Reno	Nevada	United States
12		Philadelphia	Pennsylvania	United States
13		Nashville	Tennessee	United States
14		Dallas	Texas	United States
15		Houston	Texas	United States
16		San Antonio	Texas	United States

Sponsors and Collaborators

• UCB Biopharma S.P.R.L.

Investigators

• Study Director: TzeChiang Meng, MD, Proximagen, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCB Biopharma S.P.R.L.
• ClinicalTrials.gov Identifier: NCT02161185
• Other Study ID Numbers: P261-408; 2014-001604-22
• First Posted: Jun 11, 2014
• Last Update Posted: Oct 10, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by UCB Biopharma S.P.R.L.: Epilepsy; seizure cluster; acute repetitive seizures; open-label; intranasal Midazolam; USL261; Upsher-Smith
• Additional relevant MeSH terms: Epilepsy; Seizures; Midazolam

Study Results

Participant Flow

Arm/Group Title	USL261
Arm/Group Description	USL261: 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol
Period Title: Test Dose Phase
STARTED	7
COMPLETED	7
NOT COMPLETED	0
Period Title: Test Dose Phase
STARTED	7
COMPLETED	0
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	USL261
Arm/Group Description	USL261: 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	27.0
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Death, Serious Adverse Events, Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation
Description	Number of Participants with Death, Serious Adverse Events, Treatment emergent adverse events (TEAEs) leading to subject discontinuation from study
Time Frame	Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug

Arm/Group Title	USL261
Arm/Group Description	USL261: 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol
Measure Participants	7
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Treatment Success
Description	Termination of seizure(s) within 10 minutes and no recurrence within 6 hours after study drug administration. Due to early termination of the study, this data was not analyzed.
Time Frame	Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.

Outcome Measure Data

Analysis Population Description

Not applicable. Only 6 subjects treated at least 1 seizure cluster; of the treated seizure clusters, the majority were in only 2 subjects. Analysis of this endpoint was not performed as the sponsor believed the results would not be interpretable.

Arm/Group Title	USL261
Arm/Group Description	USL261: 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol
Measure Participants	0

Adverse Events

Time Frame	Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.
Adverse Event Reporting Description	Treatment emergent
Arm/Group Title	USL261
Arm/Group Description	USL261: 5 mg, intranasal dose for seizure cluster, may repeat as indicated by protocol
All Cause Mortality
	USL261
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	USL261
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	USL261
	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)
Eye disorders
Lacrimation increased	1/7 (14.3%)
Gastrointestinal disorders
Nausea	1/7 (14.3%)
Abdominal discomfort	1/7 (14.3%)
General disorders
Product taste abnormal	1/7 (14.3%)
Fatigue	1/7 (14.3%)
Pyrexia	1/7 (14.3%)
Immune system disorders
Seasonal allergy	1/7 (14.3%)
Infections and infestations
Furuncle	1/7 (14.3%)
Injury, poisoning and procedural complications
Laceration	1/7 (14.3%)
Investigations
Oxygen saturation decreased	1/7 (14.3%)
Nervous system disorders
Somnolence	2/7 (28.6%)
Tremor	1/7 (14.3%)
Headache	1/7 (14.3%)
Psychiatric disorders
Insomnia	1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/7 (28.6%)
Epistaxis	1/7 (14.3%)
Cough	1/7 (14.3%)
Respiratory tract congestion	1/7 (14.3%)
Nasal congestion	1/7 (14.3%)

Limitations/Caveats

Early termination due to poor enrollment leading to small numbers of subjects analyzed for safety. Efficacy was not analyzed.

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 the sponsor.