EpilepsyPhase 3ARTEMIS1NCT01390220
Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients With Seizure Clusters
A Phase 3 study testing USL261 in people with Epilepsy, run by UCB Biopharma S.P.R.L. at 90 sites in 11 countries.
Trial summary
The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient 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?
- Yes, some participants may receive a placebo
- How many people
- 292 participants
- Where
- 90 sitesin 11 countries
- Study dates
- Jun 2011to Mar 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 an established diagnosis of partial or generalized epilepsy that includes 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 occurring within 6 hours from the time of cluster recognition
- A seizure cluster pattern composed of multiple (≥ 2) partial or generalized seizures
Show all 12Show fewer
- A seizure cluster pattern established > 3 months before Visit 1
- A frequency of ≥ 3 seizure clusters during the year before Visit 1
- At least 1 seizure cluster occurring ≤ 4 months before Visit 1
- Seizure cluster pattern is confirmed by a central reviewer
- Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
- Weight is 40 kg to 125 kg, inclusive
Who cannot join
- Has a neurological disorder that is likely to progress in the next year
- Has severe chronic cardio-respiratory disease
- Has had psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1
- Has a history of their stereotypical seizure cluster progressing to status epilepticus within the 2 years before Visit 1
- Has a history of acute narrow-angle glaucoma.
- 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
- Currently using a vagal nerve stimulator (VNS) unless the device has been implanted for at least 6 months and the setting stable for 4 weeks before Visit 1
Trial locations and contacts
90 sites in 11 countries.
90 sites in 11 countries
United States46 sites
United States, Colorado
Aurora, Colorado
United States, Maryland
Baltimore, Maryland
United States, Idaho
Boise, Idaho
United States, Missouri
Chesterfield, Missouri
United States, Illinois
Chicago, Illinois
United States, Ohio
Columbus, Ohio
United States, Texas
Dallas, Texas
United States, Michigan
Detroit, Michigan
United States, North Carolina
Durham, North Carolina
United States, New Jersey
Flemington, New Jersey
United States, Texas
Fort Worth, Texas
United States, California
Fresno, California
United States, Florida
Gainesville, Florida
United States, Texas
Greenville, Texas
United States, Florida
Gulf Breeze, Florida
United States, New Jersey
Hackensack, New Jersey
United States, California
Irvine, California
United States, New Hampshire
Lebanon, New Hampshire
United States, Kentucky
Lexington, Kentucky
United States, Arkansas
Little Rock, Arkansas
United States, California
Loma Linda, California
United States, Wisconsin
Madison, Wisconsin
United States, Kansas
Manhattan, Kansas
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, Virginia
Norfolk, Virginia
United States, Oklahoma
Oklahoma City, Oklahoma
United States, Pennsylvania
Philadelphia, Pennsylvania
United States, Arizona
Phoenix, Arizona
United States, Florida
Port Charlotte, Florida
United States, Oregon
Portland, Oregon
United States, Nevada
Reno, Nevada
United States, California
Sacramento, California
United States, Minnesota
Saint Paul, Minnesota
United States, Texas
San Antonio, Texas
United States, Missouri
St Louis, Missouri
United States, New York
Stony Brook, New York
United States, Florida
Tampa, Florida
United States, Texas
Temple, Texas
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
Israel6 sites
Israel
Haifa
Israel
Holon
Israel
Jerusalem
Israel
Petah Tikva
Israel
Ramat Gan
Israel
Tel Aviv
Italy6 sites
Italy
Florence
Italy
Genova
Italy
Milan
Italy
Naples
Italy
Pavia
Italy
San Fermo della Battaglia
Spain6 sites
Spain, Catalonia
Barcelona, Catalonia
Spain, Madrid
Fuencarral-El Pardo, Madrid
Spain, Catalonia
Girona, Catalonia
Spain, Madrid
Moncloa-Aravaca, Madrid
Spain, Madrid
Pozuelo de Alarcón, Madrid
Spain, Andalucia
Seville, Andalusia
Ukraine6 sites
Ukraine, Ivano-Frankivsk
Ivano-Frankivsk
Ukraine
Kharkiv
Ukraine
Odesa
Ukraine
Poltava
Ukraine
Ternopil
Ukraine
Vinnytsia
Australia5 sites
Australia, New South Wales
Chatswood, New South Wales
Australia, Vctoria
Heidelberg West, Victoria
Australia, Queensland
Herston, Queensland
Australia, Victoria
Parkville, Victoria
Australia, New South Wales
Randwick, New South Wales
Germany5 sites
Germany, Westfalen-Lippe
Bielefeld, Wetsfalen-Lippe
Germany, Nordrhein-Westfalen
Bonn, North Rhine-Westphalia
Germany, Baden-Wurttemberg
Freiburg im Breisgau, Baden-Wurttemberg
Germany, Hessen
Marburg, Hesse
Germany, Bayern
Munich, Bavaria
New Zealand2 sites
New Zealand, Canterbury
Christchurch, Canterbury
New Zealand, Auklund
Grafton, Auklund
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects With Seizure Clusters. ARTEMIS-1: Acute Rescue Therapy in Epilepsy With Midazolam Intranasal Spray-1
The purpose of this study is to examine the safety and effectiveness of USL261 for the outpatient treatment of seizure clusters.
Read the detailed description
Qualifying participants underwent an in-clinic administration (Test Dose Phase [TDP]) of two doses of USL261 (intranasal midazolam 5 mg), separated by 10 minutes, in the absence of seizures. Eligible participants were then randomized to USL261 versus Placebo in an outpatient Comparative Phase (CP). When the participant had a qualifying seizure cluster episode, as described in an individualized patient management plan, the participant's caregiver administered the double-blind dose. An open-label USL261 dose could be administered after 10 minutes and up to 6 hours after the double-blind dose, if the participant had persistent or recurrent seizures. Initial participants could not proceed to CP until an independent data safety monitoring board (DSMB) reviewed safety data from at least the first 25 participants in TDP; the DSMB performed additional safety reviews at pre-set intervals based on enrollment.
- Conditions
- Epilepsy
- Being tested
- USL261, Placebo
- Keywords
- Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment, ARTEMIS
- Medical subject headings
- Epilepsy, Severe combined immunodeficiency with sensitivity to ionizing radiation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
USL261Drug
Also called Midazolam nasal spray (MDZ NS)
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| USL261 | Experimental | intranasal midazolam 5mg Receives: Drug: USL261 |
| Placebo | Experimental | Intranasal placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
Treatment Success is defined as achieving both of the following: 1) termination of seizure(s) within 10 minutes after double-blind study drug administration, and 2) no recurrence of seizure(s) beginning 10 minutes after study drug administration to 6 hours after study drug administration. Participants who received the open-label second dose within 6 hours of administration of the double-blind dose were analyzed as having had a seizure.
Measured: 6 hours
Secondary outcomes (3)
Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
Participants with recurrence of seizure(s) >10 minutes and up to 4 hours after administration of the double-blind dose in the CP. Participants who received the open-label second dose within 4 hours of administration of the double-blind dose were analyzed as having had a seizure.
Measured: 4 hours
Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Occurrence of next seizure with a start time >10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
Measured: 24 hours
Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Time to next seizure with a start time >10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2011 (estimated)
- Study startJun 2011
- Primary completionMar 2017
- Study completionMar 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 292 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
- NCT01390220
- Sponsor's protocol ID
- P261-401
- Other IDs
- 2011-001318-32
- Acronym
- ARTEMIS1
- Status last verified
- Oct 2019
- First submitted
- 6 Jul 2011
- Last updated
- 10 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 36410152Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters-a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019 Sep;60(9):1797-1808. doi: 10.1111/epi.15159. Epub 2019 May 29.
PubMed 31140596
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects With Seizure Clusters. ARTEMIS-1: Acute Rescue Therapy in Epilepsy With Midazolam Intranasal Spray-1
- ClinicalTrials.gov ID
- NCT01390220
- Acronym / sponsor ID
- ARTEMIS1 / P261-401
- Conditions
- Epilepsy
- Keywords
- Epilepsy, seizure clusters, acute repetitive seizures, rescue treatment, ARTEMIS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 292 participants (actual)
- Lead sponsor
- UCB Biopharma S.P.R.L.Industry (pharma, biotech, devices)
- Study start
- Jun 2011 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 8 Jul 2011 (estimated)
- Results
- Posted 31 May 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 safety and effectiveness of USL261 for the outpatient treatment of seizure clusters.
Detailed description
Qualifying participants underwent an in-clinic administration (Test Dose Phase [TDP]) of two doses of USL261 (intranasal midazolam 5 mg), separated by 10 minutes, in the absence of seizures. Eligible participants were then randomized to USL261 versus Placebo in an outpatient Comparative Phase (CP). When the participant had a qualifying seizure cluster episode, as described in an individualized patient management plan, the participant's caregiver administered the double-blind dose. An open-label USL261 dose could be administered after 10 minutes and up to 6 hours after the double-blind dose, if the participant had persistent or recurrent seizures. Initial participants could not proceed to CP until an independent data safety monitoring board (DSMB) reviewed safety data from at least the first 25 participants in TDP; the DSMB performed additional safety reviews at pre-set intervals based on enrollment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| USL261 | Experimental | Drug: USL261intranasal midazolam 5mg |
| Placebo | Experimental | Drug: PlaceboIntranasal placebo |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Has a competent, adult caregiver who can recognize and observe the subject's seizure cluster episodes
- Has an established diagnosis of partial or generalized epilepsy that includes the following:
- Currently on a stable regimen of anti-epileptic drugs (AEDs) with no changes in type of AEDs since Visit 1 and for ≥ 7 days before Visit 2, with or without intermittent use of benzodiazepines at a constant dose
- Weight is 40 kg to 125 kg, inclusive
Key exclusion criteria (7 listed)
- Has a neurological disorder that is likely to progress in the next year
- Has severe chronic cardio-respiratory disease
- Has had psychogenic, non-epileptic seizure(s) within the 5 years before Visit 1
- Has a history of their stereotypical seizure cluster progressing to status epilepticus within the 2 years before Visit 1
- Has a history of acute narrow-angle glaucoma.
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 |
|---|---|---|
| USL261Also: Midazolam nasal spray (MDZ NS) | Drug | USL261 |
| Placebo | Drug | Placebo |
Primary outcome
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
Time frame: 6 hours
Treatment Success is defined as achieving both of the following: 1) termination of seizure(s) within 10 minutes after double-blind study drug administration, and 2) no recurrence of seizure(s) beginning 10 minutes after study drug administration to 6 hours after study drug administration. Participants who received the open-label second dose within 6 hours of administration of the double-blind dose were analyzed as having had a seizure.
3 secondary outcomes
Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
Time frame: 4 hours
Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Time frame: 24 hours
Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: 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 31140596Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters-a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019 Sep;60(9):1797-1808. doi: 10.1111/epi.15159. Epub 2019 May 29.
- Individual participant dataSharing planned: No
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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.
90 sites in 11 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 90 sites in 11 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 12 inclusion and 7 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 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 90 sites in United States, Israel, Italy, Spain, Ukraine and 6 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 31 May 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?
Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP) (time frame: 6 hours). 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 NCT01390220, 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 10 Oct 2019.