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Acute Repetitive SeizuresPhase 3NCT02721069

Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects

A Phase 3 study testing NRL-1 in people with Acute Repetitive Seizures and Breakthrough Seizures, run by Neurelis, Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a 12 month safety study to evaluate the safety of repeated doses of NRL-1 Read more about this study

Who is it for?
Ages 6 to 65 years
What is being tested?
NRL-1
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
5 sitesUnited States
Study dates
11 Apr 2016to 23 Jul 2020
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 6 to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Male and female subjects between the ages of 6 and 65 years, inclusive.
  • Written informed consent to participate in the study.
  • Subject has a clinical diagnosis of Epilepsy and while on a stable regimen of anti-epileptic medication, still experiences bouts of seizures (e.g. frequent break through seizures or Acute Repetitive Seizures [ARS]), and who, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control at least 1 time a month on average.
  • Subject has a qualified caregiver or medical professional available that can administer study medication in the event of a seizure.
  • Subjects having either partial or generalized Epilepsy with motor seizures or seizures with clear alteration of awareness.
  • Female subjects of childbearing potential, defined as having a menstrual cycle and who are not surgically sterile or less than two (2) years postmenopausal, must complete a pregnancy screen and agree to utilize one of the following forms of contraception during the trial and for 21 days after the last dose of study drug: abstinence, hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with spermicide), intrauterine device (IUD), or vasectomized partner (six months minimum). Subjects must have used the same method for at least one (1) month prior to starting the study.
  • No clinically significant abnormal findings in the medical history, on the physical examination or electrocardiogram (QTcF<450 msec for males and QTcF<470 msec for females).
  • Subjects and caregivers must agree to return to the study site for all study visits and must be willing to comply with all required study procedures.

Who cannot join

  • A history of clinically significant gastrointestinal, renal, hepatic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject.
  • Subject has had significant traumatic injury, major surgery or open biopsy within 30 days prior to study screening.
  • Subjects with active major depression or a past suicide attempt, or any Suicidal Ideation of 3, 4, or 5 or any Suicidal Behavior in Lifetime using Columbia-Suicide Severity Rating Scale (C-SSRS). The pediatric C-SSRS should be used for subjects age 6 to 11. The adult C SSRS should be used for subjects 12 and greater years of age.
  • A history of allergic or adverse responses to diazepam or any comparable or similar product.
  • Participation in a clinical trial other than protocol DIAZ.001.04 within 30 days prior to Day 0. Participation in an observational (non-interventional) study is not excluded as long as there are no scheduling conflicts with this study.
  • Positive serum pregnancy test (ß-hCG) at screening for subjects age 12 or greater.
  • Positive blood screen for Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive urine screen for alcohol or drugs of abuse, except marijuana use for medical reasons. When marijuana was used for medical reasons in the opinion of the investigator, it is not considered as drug abuse and the patient can be enrolled even if the marijuana metabolites in the urine revealed as positive.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Clinical Trials, Inc.

    Little Rock, Arkansas, 72205

  • New York University Comprehensive Epilepsy Center

    New York, New York, 10016

  • Thomas Jefferson University Hospital Laboratory

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A 12-Month Open-Label, Repeat-Dose Safety Study of NRL-1 in Epilepsy Subjects (DIAZ.001.05)

This is a 12 month safety study to evaluate the safety of repeated doses of NRL-1

Read the detailed description

This is a Phase 3, repeat dose, open-label, safety study in Epilepsy subjects who have frequent breakthrough seizures or Acute Repetitive Seizures (ARS). NRL-1 will be administered as needed to treat bouts of those seizures over a 12-month period of time. Doses will be defined as 5 mg, 10 mg, 15 mg, or 20 mg based on the subject's body weight. A diary will be used to record the seizure and NRL-1 administration.

Being tested
NRL-1
Keywords
Seizures, Epilepsy
Medical subject headings
Seizures, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NRL-1Drug

    Also called Intranasal diazepam

Study groups in NCT02721069
Study groupRoleWhat they receive
NRL-1ExperimentalIntranasal dose of NRL-1 will be administered at either 5 mg, 10 mg, 15 mg, or 20 mg based on the subject's body weight.
Receives: Drug: NRL-1

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Received NRL-1 (Valtoco)

    Assess the number of participants who received at least one dose of NRL-1 (Valtoco) during the study and comprised the safety population.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2016 (estimated)
  2. Study start11 Apr 2016
  3. Primary completion17 Jun 2020
  4. Study completion23 Jul 2020

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02721069
Sponsor's protocol ID
DIAZ.001.05
Status last verified
Jan 2022
First submitted
17 Mar 2016
Last updated
31 Jan 2022
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Tarquinio D, Wheless JW, Segal EB, Rabinowicz AL, Carrazana E. Safety and effectiveness of diazepam nasal spray in patients with Rett syndrome and seizure clusters: post hoc analyses from a long-term safety study and survey of severity and burden. Front Neurol. 2026 Feb 23;17:1702423. doi: 10.3389/fneur.2026.1702423. eCollection 2026.

    PubMed 41809194

  • Misra SN, Jarrar R, Stern JM, Becker DA, Carrazana E, Rabinowicz AL. Rapid Rescue Treatment with Diazepam Nasal Spray Leads to Faster Seizure Cluster Termination in Epilepsy: An Exploratory Post Hoc Cohort Analysis. Neurol Ther. 2024 Feb;13(1):221-231. doi: 10.1007/s40120-023-00568-4. Epub 2024 Jan 4.

    PubMed 38175488

  • Tarquinio D, Wheless JW, Segal EB, Misra SN, Rabinowicz AL, Carrazana E. Safety of Diazepam Nasal Spray in Pediatric Patients With Developmental Epileptic Encephalopathies: Results From a Long-term Phase 3 Safety Study. J Child Neurol. 2023 May;38(6-7):389-393. doi: 10.1177/08830738231185424. Epub 2023 Jul 16.

    PubMed 37455404

  • Cramer JA, Faught E, Davis C, Misra SN, Carrazana E, Rabinowicz AL. Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. Epilepsy Behav. 2022 Sep;134:108811. doi: 10.1016/j.yebeh.2022.108811. Epub 2022 Jul 8.

    PubMed 35816831

  • Wheless JW, Miller I, Hogan RE, Dlugos D, Biton V, Cascino GD, Sperling MR, Liow K, Vazquez B, Segal EB, Tarquinio D, Mauney W, Desai J, Rabinowicz AL, Carrazana E; DIAZ.001.05 Study Group. Final results from a Phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy. Epilepsia. 2021 Oct;62(10):2485-2495. doi: 10.1111/epi.17041. Epub 2021 Aug 21.

    PubMed 34418086

  • Miller I, Wheless JW, Hogan RE, Dlugos D, Biton V, Cascino GD, Sperling MR, Liow K, Vazquez B, Segal EB, Tarquinio D, Mauney W, Desai J, Rabinowicz AL, Carrazana E; DIAZ.001.05 Study Group. Consistent safety and tolerability of Valtoco(R) (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters: Interim results from a phase 3, long-term, open-label, repeat-dose safety study. Epilepsia Open. 2021 Sep;6(3):504-512. doi: 10.1002/epi4.12494. Epub 2021 May 13.

    PubMed 34033266

  • Penovich P, Wheless JW, Hogan RE, Guerra C, Cook DF, Carrazana E, Rabinowicz AL. Examining the patient and caregiver experience with diazepam nasal spray for seizure clusters: Results from an exit survey of a phase 3, open-label, repeat-dose safety study. Epilepsy Behav. 2021 Aug;121(Pt A):108013. doi: 10.1016/j.yebeh.2021.108013. Epub 2021 May 19.

    PubMed 34022621

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NRL-1 in people with Acute Repetitive Seizures and Breakthrough Seizures, run by Neurelis, Inc. at 5 sites in United States.

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 8 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: finished, as of the sponsor's last update on 31 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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 Jan 2022). 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?

Number of Participants Who Received NRL-1 (Valtoco) (time frame: 12 months). 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 NCT02721069, which also lists 7 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 31 Jan 2022.

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