Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects

• Sponsor: Neurelis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02721069
• Collaborator: (none)
• Enrollment: 175
• Locations: 5
• Arm: 1
• Actual Duration (Months): 51.4
• Patients Per Site: 35
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Acute Repetitive Seizures; Breakthrough Seizures	Drug: NRL-1	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 175 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12-Month Open-Label, Repeat-Dose Safety Study of NRL-1 in Epilepsy Subjects (DIAZ.001.05)
• Actual Study Start Date: Apr 11, 2016
• Actual Primary Completion Date: Jun 17, 2020
• Actual Study Completion Date: Jul 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: NRL-1; Other Names: Intranasal diazepam

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trials, Inc.	Little Rock	Arkansas	United States	72205
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	New York University Comprehensive Epilepsy Center	New York	New York	United States	10016
5	Thomas Jefferson University Hospital Laboratory	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Neurelis, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 28, 2017
• Statistical Analysis Plan - Jul 8, 2020

More Information

Publications

None provided.

• Responsible Party: Neurelis, Inc.
• ClinicalTrials.gov Identifier: NCT02721069
• Other Study ID Numbers: DIAZ.001.05
• First Posted: Mar 28, 2016
• Last Update Posted: Jan 31, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Neurelis, Inc.: Seizures; Epilepsy
• Additional relevant MeSH terms: Epilepsy; Seizures; Diazepam

Study Results

Participant Flow

Arm/Group Title	NRL-1
Arm/Group Description	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
Period Title: Overall Study
STARTED	175
COMPLETED	117
NOT COMPLETED	58

Baseline Characteristics

Arm/Group Title	NRL-1
Arm/Group Description	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
Overall Participants	175
Age (Count of Participants)
<=18 years	92 52.6%
Between 18 and 65 years	82 46.9%
>=65 years	1 0.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.3 (14.87)
Sex: Female, Male (Count of Participants)
Female	93 53.1%
Male	82 46.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 2.3%
Native Hawaiian or Other Pacific Islander	5 2.9%
Black or African American	19 10.9%
White	143 81.7%
More than one race	4 2.3%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	175 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Received NRL-1 (Valtoco)
Description	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

Outcome Measure Data

Analysis Population Description

Subjects who received at least one dose of NRL-1.

Arm/Group Title	NRL-1 5mg	NRL-1 10mg	NRL-1 15 mg	NRL-1 20mg
Arm/Group Description	Intranasal dose of NRL-1 will be administered at 5 mg based on age and weight.	Intranasal dose of NRL-1 will be administered at 10 mg based on age and weight.	Intranasal dose of NRL-1 will be administered at 15 mg based on age and weight.	Intranasal dose of NRL-1 will be administered at 20 mg based on age and weight.
Measure Participants	11	61	46	57
Count of Participants [Participants]	9 5.1%	54 NaN	46 NaN	54 NaN

Adverse Events

Time Frame	12 months
Arm/Group Title	NRL-1 5mg		NRL-1 10mg		NRL-1 15mg		NRL-1 20mg
Arm/Group Description	Intranasal dose of NRL-1 will be administered at 5, 10, 15, and 20 mg based on age and weight.		Intranasal dose of NRL-1 will be administered at 5, 10, 15, and 20 mg based on age and weight.		Intranasal dose of NRL-1 will be administered at 5, 10, 15, and 20 mg based on age and weight.		Intranasal dose of NRL-1 will be administered at 5, 10, 15, and 20 mg based on age and weight.
All Cause Mortality
	NRL-1 5mg		NRL-1 10mg		NRL-1 15mg		NRL-1 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/54 (0%)		0/46 (0%)		1/54 (1.9%)
Serious Adverse Events
	NRL-1 5mg		NRL-1 10mg		NRL-1 15mg		NRL-1 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)		20/54 (37%)		15/46 (32.6%)		13/54 (24.1%)
Cardiac disorders
Mitral Valve Prolapse	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Gastrointestinal disorders
Pancreatitis	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	1/54 (1.9%)	1
Vomiting	0/9 (0%)	0	2/54 (3.7%)	3	0/46 (0%)	0	0/54 (0%)	0
Constipation	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Large Intestinal Ulcer	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Proctalgia	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
General disorders
Pyrexia	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	1/54 (1.9%)	1
Chest Pain	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Sudden Unexplained Death in Epilepsy	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Infections and infestations
Pneumonia	0/9 (0%)	0	4/54 (7.4%)	4	1/46 (2.2%)	3	2/54 (3.7%)	2
Abscess	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Appendicitis Perforated	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Colonic Abscess	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Influenza	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Pharyngitis Streptococcal	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Injury, poisoning and procedural complications
Hip Fracture	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Joint Dislocation	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Thermal Burn	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Wound Dehiscence	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Wrist Fracture	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Metabolism and nutrition disorders
Dehydration	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Feeding Disorder	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Hyponatraemia	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Musculoskeletal and connective tissue disorders
Scoliosis	0/9 (0%)	0	2/54 (3.7%)	2	0/46 (0%)	0	0/54 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic Myeloid Leukaemia	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Colorectal Adenocarcinoma	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Leiomyoma	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Nervous system disorders
Seizure	1/9 (11.1%)	1	11/54 (20.4%)	16	8/46 (17.4%)	14	4/54 (7.4%)	5
Status Epilepticus	0/9 (0%)	0	5/54 (9.3%)	7	1/46 (2.2%)	1	1/54 (1.9%)	2
Epilepsy	0/9 (0%)	0	2/54 (3.7%)	3	1/46 (2.2%)	2	2/54 (3.7%)	3
Seizure Cluster	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	2/54 (3.7%)	4
Amnesia	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Disturbance in Attention	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Generalised tonic-clonic seizure	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Lennox-Gastaut Syndrome	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Lethargy	1/9 (11.1%)	1	0/54 (0%)	0	0/46 (0%)	0	0/54 (0%)	0
Muscle Spasticity	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Partial Seizures	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Petit Mal Epilepsy	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Postictal State	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Psychiatric disorders
Anxiety	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	1/54 (1.9%)	1
Depression	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Hallucination, Visual	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Major Depression	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Suicidal Ideation	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Reproductive system and breast disorders
Menorrhagia	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Uterine Haemorrhage	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration	0/9 (0%)	0	1/54 (1.9%)	1	1/46 (2.2%)	1	0/54 (0%)	0
Acute Respiratory Failure	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Asthma	0/9 (0%)	0	1/54 (1.9%)	1	0/46 (0%)	0	0/54 (0%)	0
Dyspnoea	0/9 (0%)	0	0/54 (0%)	0	0/46 (0%)	0	1/54 (1.9%)	1
Restrictive Pulmonary Disease	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Surgical and medical procedures
Brain Lobectomy	0/9 (0%)	0	0/54 (0%)	0	1/46 (2.2%)	1	0/54 (0%)	0
Other (Not Including Serious) Adverse Events
	NRL-1 5mg		NRL-1 10mg		NRL-1 15mg		NRL-1 20mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)		34/54 (63%)		24/46 (52.2%)		21/54 (38.9%)
Gastrointestinal disorders
Diarrhoea	2/9 (22.2%)	2	4/54 (7.4%)	4	1/46 (2.2%)	1	2/54 (3.7%)	2
Vomiting	1/9 (11.1%)	1	4/54 (7.4%)	5	2/46 (4.3%)	2	2/54 (3.7%)	4
General disorders
Pyrexia	1/9 (11.1%)	1	10/54 (18.5%)	10	3/46 (6.5%)	3	1/54 (1.9%)	1
Infections and infestations
Nasopharyngitis	1/9 (11.1%)	3	12/54 (22.2%)	13	3/46 (6.5%)	3	4/54 (7.4%)	6
Upper Respiratory Tract Infection	0/9 (0%)	0	9/54 (16.7%)	10	7/46 (15.2%)	8	4/54 (7.4%)	4
Influenza	3/9 (33.3%)	4	5/54 (9.3%)	5	3/46 (6.5%)	3	1/54 (1.9%)	1
Urinary Tract Infection	1/9 (11.1%)	2	4/54 (7.4%)	8	3/46 (6.5%)	3	3/54 (5.6%)	4
Nervous system disorders
Seizure	0/9 (0%)	0	4/54 (7.4%)	5	7/46 (15.2%)	8	2/54 (3.7%)	4
Somnolence	0/9 (0%)	0	5/54 (9.3%)	5	4/46 (8.7%)	4	2/54 (3.7%)	2
Respiratory, thoracic and mediastinal disorders
Nasal Discomfort	0/9 (0%)	0	0/54 (0%)	0	4/46 (8.7%)	11	6/54 (11.1%)	16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.