Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects

NCT02721069 | Completed Phase 3 Results

• 1 other identifier: DIAZ.001.05
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Acute Repetitive Seizures; Breakthrough Seizures

Keywords

Seizures; Epilepsy

Outcome Measures

Primary Outcomes (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.

  12 months

Study Arms (1)

NRL-1

EXPERIMENTAL

Intranasal 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.

Drug: NRL-1

Interventions

NRL-1 DRUG

Also known as: Intranasal diazepam

NRL-1

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Neurelis, Inc.: lead

Study Sites (5)

Clinical Trials, Inc.

Little Rock, Arkansas, 72205, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York University Comprehensive Epilepsy Center

New York, New York, 10016, United States

Location

Thomas Jefferson University Hospital Laboratory

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (6)

• 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.

  PMID: 38175488 DERIVED

• 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.

  PMID: 37455404 DERIVED

• 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.

  PMID: 35816831 DERIVED

• 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.

  PMID: 34418086 DERIVED

• 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.

  PMID: 34033266 DERIVED

• 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.

  PMID: 34022621 DERIVED

MeSH Terms

Conditions

Seizures; Epilepsy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Cyndi Guerra
• Organization: Neurelis, Inc.

cguerra@neurelis.com

9736156258

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 28, 2016
• Study Start: April 11, 2016
• Primary Completion: June 17, 2020
• Study Completion: July 23, 2020
• Last Updated: January 31, 2022
• Results First Posted: January 31, 2022

Record last verified: 2022-01

Locations

US (5)