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

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
diazepam nasal spray (BA)	diazepam nasal spray	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).
diazepam nasal spray (AB)	diazepam nasal spray	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).

Primary Outcome Measures

Name	Time	Method
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
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
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

Secondary Outcome Measures

Name	Time	Method
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	from 5 minutes up to 24 hours post-dose	If patient reports a change in taste associated with diazepam nasal spray, questionnaire to be completed by research staff.

Recruitment & Eligibility