Acute Repetitive Seizures, Breakthrough Seizures
Conditions
Keywords
Seizures, Epilepsy
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.
Interventions
DRUGNRL-1
Sponsors
Neurelis, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received NRL-1 (Valtoco) | 12 months | Assess the number of participants who received at least one dose of NRL-1 (Valtoco) during the study and comprised the safety population. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NRL-1 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.
NRL-1 | 175 |
| Total | 175 |
Baseline characteristics
| Characteristic | NRL-1 |
|---|---|
| Age, Categorical <=18 years | 92 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants |
| Age, Continuous | 22.3 years STANDARD_DEVIATION 14.87 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 143 Participants |
| Region of Enrollment United States | 175 Participants |
| Sex: Female, Male Female | 93 Participants |
| Sex: Female, Male Male | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 54 | 0 / 46 | 1 / 54 |
| other Total, other adverse events | 6 / 9 | 34 / 54 | 24 / 46 | 21 / 54 |
| serious Total, serious adverse events | 2 / 9 | 20 / 54 | 15 / 46 | 13 / 54 |
Outcome results
Primary
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.
Time frame: 12 months
Population: Subjects who received at least one dose of NRL-1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NRL-1 5mg | Number of Participants Who Received NRL-1 (Valtoco) | 9 Participants |
| NRL-1 10mg | Number of Participants Who Received NRL-1 (Valtoco) | 54 Participants |
| NRL-1 15 mg | Number of Participants Who Received NRL-1 (Valtoco) | 46 Participants |
| NRL-1 20mg | Number of Participants Who Received NRL-1 (Valtoco) | 54 Participants |