Acute Repetitive SeizuresPhase 1NCT02724423
Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects
A Phase 1 study testing NRL-1 in people with Acute Repetitive Seizures, run by Neurelis, Inc. at 4 sites in United States.
Trial summary
This study evaluates the pharmacokinetic and safety of NRL-1 in epilepsy subjects. Subjects will receive a single intranasal dose of NRL-1 of either 5 mg, 10 mg, 15 mg or 20 mg and will be based on the subject's body weight. Read more about this study
- Who is it for?
- Ages 6 to 65 years
- Conditions the study is for
- Acute Repetitive Seizures
- What is being tested?
- NRL-1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 4 sitesUnited States
- Study dates
- 30 Jun 2016to 10 Sep 2019
- Phase
- Phase 1
- 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.
- Body mass index (BMI) not to exceed 35 kg/m², inclusive.
- Subject has a clinical diagnosis of Epilepsy and, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control.
- Subjects having either partial or generalized Epilepsy with motor seizures or seizures with clear alteration of awareness are eligible for enrollment.
- 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).
- No clinically significant abnormal findings in the medical history, on the physical examination, ECG (corrected QT interval [QTcF] < 450 msec for males and QTcF < 470 msec for females), or clinical laboratory results during screening.
- 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
- Subject is undergoing intracranial EEG monitoring.
- A history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, severe seasonal or non-seasonal allergies, nasal polyps or any nasal passage abnormality that could interfere with nasal spray administration, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
- 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 documented on the Baseline/Screening C-SSRS. The children 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.
- Any Suicidal Ideation of 3, 4, or 5 or any Suicidal Behavior in Lifetime using C-SSRS.
- A history of allergic or adverse responses to diazepam or any comparable or similar product.
Show all 18Show fewer
- Subjects who (for whatever reason) have been on an abnormal diet (such as one that severely restricts specific basic food groups [e.g., ketogenic diet], limits calories [e.g., fast], and/or requires the use of daily supplements as a substitute for the foods typically eaten at mealtimes), during the four (4) weeks preceding the study.
- Subjects who donated blood or plasma within 30 days of the first dose of study drug.
- Participation in a clinical trial within 30 days prior to the first dose of study drug. Participation in an observational (non-interventional) study is not excluded as long as there are no scheduling conflicts with this study.
- Inadequate or difficult venous access that may jeopardize the quality or timing of the PK samples.
- Female subjects who are trying to conceive, are pregnant, or are lactating.
- Positive serum pregnancy test (ß-hCG) at screening or urine pregnancy test prior to each administration of study drug for all women of childbearing potential.
- Positive blood screen on subjects age 12 or greater for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbSAg), or Hepatitis C, or a positive urine screen for alcohol, drugs of abuse, or cotinine. 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.
- Treatment with phenobarbital or primidone within 30 days of the anticipated dosing visit (i.e., baseline).
- Treatment with warfarin or dabigatran or other blood thinners within 30 days of the anticipated dosing visit (i.e., baseline).
- Treatment with any diazepam containing products within 14 days of the anticipated dosing visit (i.e., baseline).
- Use of nasal decongestants or nasal steroids within 7 days prior to the screening visit or during the study.
- Subject does not have the flu, rhinitis or any other nasal condition that would impact absorption of intranasal diazepam.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Virginia
Charlottesville, Virginia, 22903
Le Bonheur Children's Hospita
Memphis, Tennessee, 38103
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: An Open-Label, Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects Under Seizure and Normal Conditions
This study evaluates the pharmacokinetic and safety of NRL-1 in epilepsy subjects. Subjects will receive a single intranasal dose of NRL-1 of either 5 mg, 10 mg, 15 mg or 20 mg and will be based on the subject's body weight.
Read the detailed description
Diazepam rectal gel (Diastat) is the only formulation of diazepam indicated for the management of selected, refractory patients with epilepsy on stable regimens of antiepileptic drugs (AEDs) who require intermittent use of diazepam to control bouts of increased seizure activity, i.e., Acute Repetitive Seizures (ARS).
A diazepam nasal spray is being developed for patients who experience ARS to provide an alternative more convenient and acceptable route of diazepam administration.
- Conditions
- Acute Repetitive Seizures
- Being tested
- NRL-1
- Keywords
- epilepsy, seizure
- Medical subject headings
- Epilepsy, Seizures
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 group | Role | What they receive |
|---|---|---|
| NRL-1 Ictal | Experimental | During the ictal or peri-ictal setting, a single 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. Receives: Drug: NRL-1 |
| NRL-1 Inter-Ictal | Experimental | During the inter-ictal setting, a single 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. Receives: Drug: NRL-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period
Evaluate the pharmacokinetics (PK), in terms of Cmax, of diazepam following a single intranasal dose of NRL-1 (diazepam nasal spray) administered to epilepsy subjects in the ictal or peri-ictal state (defined as either during or immediately following a seizure), where the seizure involved motor activity or alteration of awareness compared with the normal (non-seizing) state. The epileptic condition (ictal/peri-ictal, interictal) had minimal impact on diazepam nasal spray pharmacokinetics.
Measured: Blood samples were obtained at 0, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, and 6 hours after dosing. If feasible, samples were drawn at 8 and 12 hours post-dose but were excluded from PK analysis.
Secondary outcomes (1)
The AUC of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period
Evaluate the pharmacokinetics (PK), in terms of AUC, of diazepam following a single intranasal dose of NRL-1 (diazepam nasal spray) administered to epilepsy subjects in the ictal or peri-ictal state (defined as either during or immediately following a seizure), where the seizure involved motor activity or alteration of awareness compared with the normal (non-seizing) state. The epileptic condition (ictal/peri-ictal, interictal) had minimal impact on diazepam nasal spray pharmacokinetics.
Measured: Blood samples were obtained at 0, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, and 6 hours after dosing. If feasible, samples were drawn at 8 and 12 hours post-dose but were excluded from PK analysis.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2016 (estimated)
- Study start30 Jun 2016
- Primary completion10 Apr 2019
- Study completion10 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Repetitive SeizuresStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurelis, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02724423
- Sponsor's protocol ID
- DIAZ.001.04
- Status last verified
- Aug 2021
- First submitted
- 17 Mar 2016
- Last updated
- 5 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Hogan RE, Tarquinio D, Sperling MR, Klein P, Miller I, Segal EB, Rabinowicz AL, Carrazana E. Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: A phase 1, open-label study. Epilepsia. 2020 May;61(5):935-943. doi: 10.1111/epi.16506. Epub 2020 Apr 27.
PubMed 32338380
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects Under Seizure and Normal Conditions
- ClinicalTrials.gov ID
- NCT02724423
- Acronym / sponsor ID
- DIAZ.001.04
- Conditions
- Acute Repetitive Seizures
- Keywords
- epilepsy, seizure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Neurelis, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jun 2016 (actual)
- Primary completion
- 10 Apr 2019 (actual)
- Study completion
- 10 Sep 2019 (actual)
- First posted
- 31 Mar 2016 (estimated)
- Results
- Posted 5 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the pharmacokinetic and safety of NRL-1 in epilepsy subjects. Subjects will receive a single intranasal dose of NRL-1 of either 5 mg, 10 mg, 15 mg or 20 mg and will be based on the subject's body weight.
Detailed description
Diazepam rectal gel (Diastat) is the only formulation of diazepam indicated for the management of selected, refractory patients with epilepsy on stable regimens of antiepileptic drugs (AEDs) who require intermittent use of diazepam to control bouts of increased seizure activity, i.e., Acute Repetitive Seizures (ARS).
A diazepam nasal spray is being developed for patients who experience ARS to provide an alternative more convenient and acceptable route of diazepam administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NRL-1 Ictal | Experimental | Drug: NRL-1During the ictal or peri-ictal setting, a single 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 Inter-Ictal | Experimental | Drug: NRL-1During the inter-ictal setting, a single 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. |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female subjects between the ages of 6 and 65 years, inclusive.
- Written informed consent to participate in the study.
- Body mass index (BMI) not to exceed 35 kg/m², inclusive.
- Subject has a clinical diagnosis of Epilepsy and, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control.
- Subjects having either partial or generalized Epilepsy with motor seizures or seizures with clear alteration of awareness are eligible for enrollment.
Key exclusion criteria (18 listed)
- Subject is undergoing intracranial EEG monitoring.
- A history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease, severe seasonal or non-seasonal allergies, nasal polyps or any nasal passage abnormality that could interfere with nasal spray administration, or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
- 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 documented on the Baseline/Screening C-SSRS. The children 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.
- Any Suicidal Ideation of 3, 4, or 5 or any Suicidal Behavior in Lifetime using C-SSRS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NRL-1Also: Intranasal diazepam | Drug | NRL-1 Ictal, NRL-1 Inter-Ictal |
Primary outcome
Cmax of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period
Time frame: Blood samples were obtained at 0, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, and 6 hours after dosing. If feasible, samples were drawn at 8 and 12 hours post-dose but were excluded from PK analysis.
Evaluate the pharmacokinetics (PK), in terms of Cmax, of diazepam following a single intranasal dose of NRL-1 (diazepam nasal spray) administered to epilepsy subjects in the ictal or peri-ictal state (defined as either during or immediately following a seizure), where the seizure involved motor activity or alteration of awareness compared with the normal (non-seizing) state. The epileptic condition (ictal/peri-ictal, interictal) had minimal impact on diazepam nasal spray pharmacokinetics.
1 secondary outcome
The AUC of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period
Time frame: Blood samples were obtained at 0, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, and 6 hours after dosing. If feasible, samples were drawn at 8 and 12 hours post-dose but were excluded from PK analysis.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32338380Hogan RE, Tarquinio D, Sperling MR, Klein P, Miller I, Segal EB, Rabinowicz AL, Carrazana E. Pharmacokinetics and safety of VALTOCO (NRL-1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri-ictal) and nonseizure (interictal) conditions: A phase 1, open-label study. Epilepsia. 2020 May;61(5):935-943. doi: 10.1111/epi.16506. Epub 2020 Apr 27.
- Individual participant dataSharing planned: Undecided
Related trials for Acute Repetitive Seizures
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NRL-1 in people with Acute Repetitive Seizures, run by Neurelis, Inc. at 4 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 18 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 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 5 Oct 2021). 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?
Cmax of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period (time frame: Blood samples were obtained at 0, 15, 30, and 45 minutes, and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, and 6 hours after dosing. If feasible, samples were drawn at 8 and 12 hours post-dose but were excluded from PK analysis.). 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 NCT02724423, which also lists 1 linked publication.
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 5 Oct 2021.