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

Overview

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

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Crossover Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: April 2016

Interventions

• Drug: diazepam nasal spray
  • 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.

Arms, Groups and Cohorts

• Experimental: diazepam nasal spray (AB)
  • 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).
• Experimental: diazepam nasal spray (BA)
  • 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).

Clinical Trial Outcome Measures

Primary Measures

• Maximum measured plasma concentration (Cmax)
  • Time Frame: 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)
  • Time Frame: 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)
  • Time Frame: 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)
  • Time Frame: within 15 minutes prior to dosing and at specified time points up to 24 hours post-dose

Secondary Measures

• Number of patients with adverse events (AEs) including serious AEs
  • Time Frame: up to 21 days
• Change in focused nasal exam
  • Time Frame: within 30 minutes prior to dosing and at specified time points up to 24 hours post-dose
• Taste change questionnaire
  • Time Frame: 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • Acorda Therapeutics
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • David Squillacote, MD, Study Director, Acorda Therapeutics