A Pharmacokinetic Study to Assess Dose Proportionality, Safety and Tolerability of Diazepam Nasal Spray in Healthy Adult Volunteers

Study Overview
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Brief Summary
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This is a single-center, two-period, randomized, open-label, crossover pharmacokinetic (PK) study in healthy adult volunteers to evaluate dose proportionality of diazepam nasal spray using two dose levels

Official Title
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A Two-Period, Randomized, Open-Label, Crossover Pharmacokinetic Study to Assess Dose Proportionality, Safety and Tolerability of Diazepam Nasal Spray in Healthy Adult Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: diazepam nasal spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening body weight 88 to 111 kg, inclusive; General good health with no clinically significant abnormalities that would affect ability to complete study as determined by medical history, physical examination, visual evaluation of the septum and turbinates to document baseline anatomy, electrocardiogram, clinical laboratory test results; Negative drug and alcohol testing; Negative pregnancy test for female subjects of childbearing potential. Exclusion Criteria: Subject who is not surgically sterile or female subject who is less than 2 years postmenopausal, and who does not agree to use a highly effective birth control method during the study and up to 3 months after the last dose of investigational product; In the judgment of the Investigator, any clinically significant abnormality (such as septal perforations) or illness that would interfere with participation in this study as determined by medical history, physical examination (including visual exam of septum and turbinates), ECG, clinical laboratory results, or other screening safety tests; Any other condition and/or situation that causes the investigator to deem a subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: diazepam nasal spray (AB)<br>Each subject will receive two single doses of investigational product (DL1, DL2) with a 14-day washout between the doses. The order in which the doses are administered will be randomized, with subjects assigned to 1 of 2 treatment sequences: DL1 (A) followed by DL2 (B), or the reverse order (BA). | Drug: diazepam nasal spray<br>* diazepam nasal spray at two dose levels (DL). One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.<br>* Other names: PLUMIAZ™ (diazepam) Nasal Spray;|
| Experimental: diazepam nasal spray (BA)<br>Each subject will receive two single doses of investigational product (DL1, DL2) with a 14-day washout between the doses. The order in which the doses are administered will be randomized, with subjects assigned to 1 of 2 treatment sequences: DL1 (A) followed by DL2 (B), or the reverse order (BA). | Drug: diazepam nasal spray<br>* diazepam nasal spray at two dose levels (DL). One dose of diazepam nasal spray is administered as two intranasal sprays; one in each nostril using a nasal spray device.<br>* Other names: PLUMIAZ™ (diazepam) Nasal Spray;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured plasma concentration (Cmax) |  | within 15 minutes prior to dosing and at specified time points up to 24 hours post-dose | 
| Area under the concentration curve from time 0 to the concentration at 24 hours (AUC0-24) |  | within 15 minutes prior to dosing and at specified time points up to 24 hours post-dose | 
| Area under the concentration curve from time 0 to infinity (AUCinf) |  | within 15 minutes prior to dosing and at specified time points up to 24 hours post-dose | 
| Apparent total body clearance of drug from plasma (CL/F) |  | within 15 minutes prior to dosing and at specified time points up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) including serious AEs |  | up to 21 days | 
| Change in focused nasal exam |  | within 30 minutes prior to dosing and at specified time points up to 24 hours post-dose | 
| Taste change questionnaire | If patient reports a change in taste associated with diazepam nasal spray, questionnaire to be completed by research staff. | from 5 minutes up to 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dose proportionality, diazepam nasal spray