Trial Outcomes & Findings for Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects (NCT NCT02724423)

Last Updated: 2021-10-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

57 participants

Primary outcome timeframe

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 posted on

2021-10-05

Participant Flow

Participant milestones

Participant milestones
Measure	NRL-1 Single intranasal doses of NRL-1 (diazepam nasal spray) in epilepsy subjects during the ictal/peri-ictal period and single intranasal doses of NRL-1 (diazepam nasal spray) to the same subjects during the inter-ictal period.
Overall Study STARTED	57
Overall Study COMPLETED	54
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Repeat-Dose Pharmacokinetics Study of NRL-1 in Epilepsy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NRL-1 n=57 Participants Single intranasal doses of NRL-1 (diazepam nasal spray) in epilepsy subjects during the ictal/peri-ictal period and single intranasal doses of NRL-1 (diazepam nasal spray) to the same subjects during the inter-ictal period.
Age, Categorical <=18 years	20 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	28.1 years STANDARD_DEVIATION 15.33 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	57 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: Of the 57 subjects who received NRL-1 and were included in the safety analysis dataset, there were 47 subjects per arm (82.5%) in the pharmacokinetic analysis dataset.

Outcome measures

Outcome measures
Measure	NRL-1 ICTAL/PERI-ICTAL n=47 Participants NRL-1 ICTAL/PERI-ICTAL: This was a Phase 1, open-label, PK Study of Diazepam After Single Intranasal Doses of NRL-1 Administered to epilepsy Subjects During the Ictal or Peri-ictal Period.	NRL-1 INTER-ICTAL n=47 Participants NRL-1 INTER-ICTAL: This was a Phase 1, open-label, PK Study of Diazepam After Single Intranasal Doses of NRL-1 Administered to epilepsy Subjects During the Inter-ictal Period.
Cmax of Diazepam After Single Intranasal Doses of NRL-1 (Diazepam Nasal Spray) Administered to Epilepsy Subjects During the Ictal or Peri-ictal Period	135 ng/mL Geometric Coefficient of Variation 88.6	153 ng/mL Geometric Coefficient of Variation 81.2

SECONDARY outcome

Population: Of the 57 subjects who received NRL-1 and were included in the safety analysis dataset, there were 47 subjects per arm (82.5%) in the pharmacokinetic analysis dataset.

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.

Outcome measures

Outcome measures
Measure	NRL-1 ICTAL/PERI-ICTAL n=47 Participants NRL-1 ICTAL/PERI-ICTAL: This was a Phase 1, open-label, PK Study of Diazepam After Single Intranasal Doses of NRL-1 Administered to epilepsy Subjects During the Ictal or Peri-ictal Period.	NRL-1 INTER-ICTAL n=47 Participants NRL-1 INTER-ICTAL: This was a Phase 1, open-label, PK Study of Diazepam After Single Intranasal Doses of NRL-1 Administered to epilepsy Subjects During the Inter-ictal Period.
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	435 ng*hr/mL Geometric Coefficient of Variation 85.0	502 ng*hr/mL Geometric Coefficient of Variation 78.1

Adverse Events

NRL-1

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	NRL-1 n=57 participants at risk 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
Nervous system disorders Recurrent seizures	1.8% 1/57 • Number of events 1 • Up to 65 days
Nervous system disorders Static encephalopathy	1.8% 1/57 • Number of events 1 • Up to 65 days

Other adverse events

Other adverse events
Measure	NRL-1 n=57 participants at risk 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
Nervous system disorders Dysgeusia	5.3% 3/57 • Number of events 3 • Up to 65 days
Infections and infestations Nasopharyngitis	3.5% 2/57 • Number of events 2 • Up to 65 days
Respiratory, thoracic and mediastinal disorders Nasal Discomfort	3.5% 2/57 • Number of events 2 • Up to 65 days
Nervous system disorders Seizure	3.5% 2/57 • Number of events 2 • Up to 65 days

Additional Information

Sunita Misra, M.D. Medical Director

Neurelis, Inc.

Phone: (832) 257-1975

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place