An Open-Label, Safety and Tolerability Study of Chronic Intermittent Use of Diazepam Nasal Spray.

Study Overview
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Brief Summary
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This study will assess long-term safety and tolerability of repeat dose diazepam nasal spray in adolescents and adults with cluster seizures, with a focus on potential local effects (changes in nasal mucosa, olfaction, and taste).

Official Title
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Multi-center, Open-label, Study of Safety and Tolerability of Chronic Intermittent Usage of Diazepam Nasal Spray in Adolescents and Adult Patients With Cluster Seizures, Including Assessment of Olfaction and Reported Changes in Taste.

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: diazepam nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of drug-resistant epilepsy Patients who experience multiple episodes of acute repetitive seizures requiring at least one concomitant antiepileptic drug (AED) Occurrence of at least 3 seizure clusters within the past 12 months, including at least one cluster in the 4 months prior to the Screening Visit A caregiver must consent to participate together with the subject for purposes of observation and data collection The caregiver must be present when the investigational product is administered Screening body weight between 26 to 111 kg, inclusive Exclusion Criteria: Female subject who is pregnant, breastfeeding, or planning to become pregnant Presence or history of any abnormality or illness that may affect the absorption, distribution, metabolism or elimination of diazepam Known allergy or hypersensitivity to diazepam, related drugs, or any of the formulation components Positive screening test for ethanol or other drugs of abuse Unable to receive medications intranasally

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: diazepam nasal spray (Adults)<br>One dose of diazepam nasal spray is two intranasal sprays; one in each nostril using a nasal spray device. The dose is administered while the subject is sitting up or lying down. | Drug: diazepam nasal spray<br> <br> |
| Experimental: Diazepam Nasal Spray (Adolescents)<br>One dose of diazepam nasal spray is two intranasal sprays; one in each nostril using a nasal spray device. The dose is administered while the subject is sitting up or lying down. | Drug: diazepam nasal spray<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Olfactory Changes as Measured by the Smell Identification Test (SIT) | The SIT is a 50-item multiple-choice standardized test of olfactory function. Scoring of the test in the ability to smell ranges from normal (Normosmia: score 35 - 40 Women; 34 - 40 Men); to inability to smell (Anosmia score 6 - 18); or Malingering (not engaged in the test) ranges 0 - 5. | Screening, weeks 12, 24, 36, 48 and 51 | 
| Change From Baseline (Screening) in Nasal Mucosa. | Change from baseline treatment visits using a focused nasal exam was based on a scale of nasal irritation none to Grade 4 septal perforation. | Screening, Weeks 12, 24, 36, 48 and 51 | 
| Change in Taste as Measured by a Taste Change Questionnaire | Change in taste questionnaire was administered to subjects at every study visit only if the subject complained of a change in taste or as needed to report a related AE. The taste change profile included sweet, salty, sour, bitter, oily, sharp, chalky, metallic. The subject rated the change on a 10-point scale ranging from a weak change (1) to very strong (10). | Weeks 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clusters, Acute repetitive seizures, Cluster Seizures, Seizures