A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Safety, Efficacy and Pharmacokinetics of DPI 386 Nasal Gel for the Prevention and Treatment of Nausea Associated with Motion Sickness in Senior Subjects With Open-Label Follow-Up

This Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study with open-label follow-up to identify the safety, efficacy and pharmacokinetics of a repeated-dose regimen of DPI 386 nasal gel (intranasal scopolamine gel) for the prevention and treatment of nausea associated with motion sickness. The study will have two arms: DPI-386 nasal gel and placebo nasal gel for Treatment Day 1. Treatment Day 1 will include 50 subjects per arm, for a total of 100 subjects (n=100). All 100 subjects from Treatment Day 1 will receive open-label DPI-386 Nasal Gel for Treatment Days 2-4 (50 of these were originally randomized to receive placebo prior to receipt of the investigational product.).

Treatment Day 1 will be conducted aboard an ocean-going vessel to obtain data in an operationally relevant real world environment and within 30 days of Treatment Day 1, Treatment Days 2-4 will take place at the clinical site.

Inclusion Criteria:

1. Provision of a signed and dated Informed Consent Form (ICF).

2. Stated willingness to comply with all study procedures and availability for the duration of the study.

3. Male or female, aged 55 and over.

4. In good general health as evidenced by medical history with no recent history or current diagnosis of uncontrolled clinical problems as assessed by the Principal Investigator (PI) or qualified designee.

5. Ability to take intranasal medication and willingness to adhere to the study schedule and time constraints.

6. Agreement to adhere to the following lifestyle compliance considerations:

   • Refrain from consumption of grapefruit and any substance containing grapefruit for seven days prior to, during, and for seven days after the three Treatment Days.
   • Abstain from alcohol for 24 hours prior to first dose of study medication and during the three Treatment Days.

Exclusion Criteria:

1. Known allergic reactions to scopolamine or other anticholinergics.

2. Currently prescribed any of the following medication types and used within the specified washout periods below:

   • any form of scopolamine (including Transderm Scop®) (washout 5 days)
   • belladonna alkaloids (washout 2 weeks),
   • antihistamines (including meclizine) (washout 2 weeks),
   • tricyclic antidepressants (washout 2 weeks),
   • muscle relaxants (washout 4 days) and
   • nasal decongestants (washout 4 days)

3. Hospitalization or significant surgery requiring hospital admittance within the past six months.

4. Treatment with another investigational drug or other intervention within the past 30 days.

5. Having donated blood or plasma or suffered significant blood loss within the past 30 days.

6. Having any of the following medical conditions within the last two years or if any of the following medical conditions were experienced more than two years ago and are deemed clinically significant by the PI or qualified designee:

   • Significant gastrointestinal disorder, asthma, or seizure disorders.
   • History of cardiovascular disease.
   • History of vestibular disorders.
   • History of narrow-angle glaucoma.
   • History of urinary retention problems.
   • History of alcohol or drug abuse.
   • Nasal, nasal sinus, or nasal mucosa surgery.

Publication

This study is double-blinded placebo controlled for all treatment arms on Treatment Day 1. All DPI-386 Nasal Gel and placebo nasal gel vials are opaque and indistinguishable. The DPI-386 Nasal Gel and placebo nasal gels are identical in color and viscosity, and without identifiable smell. Treatment Days 2-4 are open-label.