EpilepsyPhase 3NCT01529034
Study to Evaluate the Long-term Safety and Tolerability of USL261 in Patients With Seizure Clusters
A Phase 3 study testing USL261 in people with Epilepsy, run by UCB Biopharma S.P.R.L. at 58 sites in 10 countries.
Trial summary
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Epilepsy
- What is being tested?
- USL261
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 175 participants
- Where
- 58 sitesin 10 countries
- Study dates
- Jul 2012to Apr 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
58 sites in 10 countries.
58 sites in 10 countries
United States31 sites
United States, Colorado
Aurora, Colorado
United States, Maryland
Baltimore, Maryland
United States, Idaho
Boise, Idaho
United States, Illinois
Chicago, Illinois
United States, Texas
Dallas, Texas
United States, Michigan
Detroit, Michigan
United States, North Carolina
Durham, North Carolina
United States, California
Fresno, California
United States, Texas
Greenville, Texas
United States, New Jersey
Hackensack, New Jersey
United States, New Hampshire
Lebanon, New Hampshire
United States, Kentucky
Lexington, Kentucky
United States, Arkansas
Little Rock, Arkansas
United States, Tennessee
Memphis, Tennessee
United States, Tennessee
Nashville, Tennessee
United States, Connecticut
New Haven, Connecticut
United States, New York
New York, New York
United States, Oklahoma
Oklahoma City, Oklahoma
United States, Pennsylvania
Philadelphia, Pennsylvania
United States, Arizona
Phoenix, Arizona
United States, Florida
Port Charlotte, Florida
United States, California
Sacramento, California
United States, Minnesota
Saint Paul, Minnesota
United States, Arizona
Scottsdale, Arizona
United States, Missouri
St Louis, Missouri
United States, New York
Stony Brook, New York
United States, New York
The Bronx, New York
United States, Arizona
Tucson, Arizona
United States, California
Ventura, California
United States, Florida
Wellington, Florida
United States, North Carolina
Winston-Salem, North Carolina
Ukraine6 sites
Ukraine
Ivano-Frankivsk
Ukraine
Kharkiv
Ukraine
Odesa
Ukraine
Poltava
Ukraine
Ternopil
Ukraine
Vinnytsa
Germany4 sites
Germany
Bielefeld, Westfalen-Lippe
Germany
Bonn, North Rhine-Westphalia
Germany
Marberg, Hesse
Germany
München, Bavaria
Australia3 sites
Australia, Victoria
Heidelberg West, Victoria
Australia, Victoria
Parkville, Victoria
Australia, New South Wales
Randwick, New South Wales
Canada3 sites
Canada
Montreal, Ontario
Canada, Toronto
Toronto, Ontario
Canada
Toronto, Quebec
About this study
Official title: An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.
Read the 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.
- Conditions
- Epilepsy
- Being tested
- USL261
- Keywords
- Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
USL261Drug
| Study group | Role | What they receive |
|---|---|---|
| USL261 | Experimental | Intranasal midazolam 5 mg Receives: Drug: USL261 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Safety Observation
Duration of participant study participation for collection of long term safety data
Measured: 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
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.
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Laboratory Abnormalities Meeting Predefined Criteria
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)
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities Physical Examination
Participants with abnormal findings, at any time post baseline, on physical examination considered clinically significant by the investigator.
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities on Neurologic Examination
Participants with abnormal findings, at any time post baseline, on neurologic examination considered clinically significant by the investigator
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Clinically Significant Abnormalities on Nasal Examination
Participants with abnormal findings, at any time post baseline, on nasal examination considered clinically significant by the investigator
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participant Change in B-SIT Score
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.
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Participants With Suicidal Ideation
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.
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Emergency Room/Emergency Medical Service Visits
Participants requiring emergency room (ER)/emergency medical service (EMS) visit within 24 hours after any USL261 treated seizure cluster (including for continued seizures)
Measured: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.
Secondary outcomes (1)
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
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)
Measured: 6 hours after first dose of USL261 for each treated seizure cluster
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2012 (estimated)
- Study startJul 2012
- Primary completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- UCB Biopharma S.P.R.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01529034
- Sponsor's protocol ID
- P261-402
- Other IDs
- 2011-004109-25
- Status last verified
- Jan 2023
- First submitted
- 3 Feb 2012
- Last updated
- 20 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Meng TC, Szaflarski JP, Chen L, Brunnert M, Campos R, Van Ess P, Pullman WE, Fakhoury T. Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial. Epilepsy Behav. 2023 Jan;138:108989. doi: 10.1016/j.yebeh.2022.108989. Epub 2022 Nov 18.
PubMed 36410152Wheless JW, Meng TC, Van Ess PJ, Detyniecki K, Sequeira DJ, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial. Epilepsia. 2019 Sep;60(9):1809-1819. doi: 10.1111/epi.16300. Epub 2019 Jul 29.
PubMed 31353457
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Safety Study of USL261 in the Outpatient Treatment of Subjects With Seizure Clusters
- ClinicalTrials.gov ID
- NCT01529034
- Acronym / sponsor ID
- P261-402
- Conditions
- Epilepsy
- Keywords
- Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 175 participants (actual)
- Lead sponsor
- UCB Biopharma S.P.R.L.Industry (pharma, biotech, devices)
- Study start
- Jul 2012 (actual)
- Primary completion
- Apr 2017 (actual)
- First posted
- 8 Feb 2012 (estimated)
- Results
- Posted 25 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the long-term safety and tolerability of USL261 in the treatment of seizure clusters.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| USL261 | Experimental | Drug: USL261Intranasal midazolam 5 mg |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| USL261 | Drug | USL261 |
Primary outcome
Duration of Safety Observation
Time frame: 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
Participants Meeting Predefined Safety Criteria for Vital Signs
Time frame: 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.
Participants With Laboratory Abnormalities Meeting Predefined Criteria
Time frame: 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)
Participants With Clinically Significant Abnormalities Physical Examination
Time frame: 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.
Participants With Clinically Significant Abnormalities on Neurologic Examination
Time frame: 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
Participants With Clinically Significant Abnormalities on Nasal Examination
Time frame: 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
Participant Change in B-SIT Score
Time frame: 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.
Participants With Suicidal Ideation
Time frame: 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.
Emergency Room/Emergency Medical Service Visits
Time frame: 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)
1 secondary outcome
Number of Treated Seizure Clusters Meeting Criteria for Treatment Success
Time frame: 6 hours after first dose of USL261 for each treated seizure cluster
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36410152Meng TC, Szaflarski JP, Chen L, Brunnert M, Campos R, Van Ess P, Pullman WE, Fakhoury T. Psychosocial outcomes of repeated treatment of seizure clusters with midazolam nasal spray: Results of a phase 3, open-label extension trial. Epilepsy Behav. 2023 Jan;138:108989. doi: 10.1016/j.yebeh.2022.108989. Epub 2022 Nov 18.
- Derived from this study: PubMed 31353457Wheless JW, Meng TC, Van Ess PJ, Detyniecki K, Sequeira DJ, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial. Epilepsia. 2019 Sep;60(9):1809-1819. doi: 10.1111/epi.16300. Epub 2019 Jul 29.
- Individual participant dataSharing planned: No
Related trials for Epilepsy
RecruitingObservational study
Evaluation and Treatment of Neurosurgical Disorders
Neurologic Disorders
RecruitingPhase 1
Investigation of Blood-Brain-Barrier Breakdown Using Manganese Magnetic Resonance Imaging in Drug-Resistant Epilepsy
Epilepsy
RecruitingPhase 3
A Study of EPX-100 (Clemizole Hydrochloride) in Participants With Dravet Syndrome
Dravet Syndrome
Active, not recruitingPhase 2
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Tuberous Sclerosis Complex, Epilepsy
RecruitingPhase 4
Early Post-Traumatic Seizures Prevention Trial (E-PTS Trial)
Seizures, Traumatic Brain Injuries
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
58 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing USL261 in people with Epilepsy, run by UCB Biopharma S.P.R.L. at 58 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 58 sites in United States, Ukraine, Germany, Australia, Canada and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Duration of Safety Observation (time frame: From Baseline/(Screening) to End of Safety-Follow-up (up to 56 months) as per assessment table of the study.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01529034, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2023; AzTrials last refreshed its copy on 30 Oct 2026.