Clinical trial NCT02721069: Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects
Official title: A 12-Month Open-Label, Repeat-Dose Safety Study of NRL-1 in Epilepsy Subjects (DIAZ.001.05)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Repetitive Seizures
Breakthrough Seizures
Keywords: Seizures
Epilepsy
Lead sponsor: Neurelis, Inc.
Sponsor class: INDUSTRY
First posted: 2016-03-28
Enrollment: 175
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects between the ages of 6 and 65 years, inclusive.
2. Written informed consent to participate in the study.
3. 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.
4. Subject has a qualified caregiver or medical professional available that can administer study medication in the event of a seizure.
5. Subjects having either partial or generalized Epilepsy with motor seizures or seizures with clear alteration of awareness.
6. 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.
7. 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).
8. 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.

Exclusion Criteria:

1. 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.
2. Subject has had significant traumatic injury, major surgery or open biopsy within 30 days prior to study screening.
3. 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.
4. A history of allergic or adverse responses to diazepam or any comparable or similar product.
5. 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.
6. Positive serum pregnancy test (ß-hCG) at screening for subjects age 12 or greater.
7. 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.

Primary outcomes:
measure: Number of Participants Who Received NRL-1 (Valtoco)
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Trials, Inc.
state: Arkansas
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: New York University Comprehensive Epilepsy Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital Laboratory
state: Pennsylvania
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.