Nasal Gel Under Military Operational Conditions for the Prevention of Nausea Associated With Motion Sickness

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Safety and Efficacy of DPI-386 Nasal Gel Under Military Operational Conditions for the Prevention of Nausea Associated With Motion Sickness

This multi-site Phase 3 clinical trial is a randomized, double-blind, placebo-controlled and open label active-controlled study to identify the safety and efficacy of a repeated-dose regimen of DPI-386 nasal gel (intranasal scopolamine gel) for the prevention and treatment of motion sickness. The study will be conducted aboard Navy fleet or Marine ships undergoing military operations to obtain data in an operationally relevant real world environment.

The study will have three arms: DPI-386 nasal gel, placebo nasal gel, and Transderm Scop® (1.5 mg/72 hours; transdermal scopolamine patch [TDS], the current standard of care for the treatment of motion sickness). The study will include 100 subjects per arm, for a total of 300 subjects (n=300). Multiple ships and ships' crews will be used, until the required enrollment is completed. The DPI-386 Nasal Gel and placebo nasal gel arms will be double-blinded, whereas the TDS arm will remain unblinded. Both DPI-386 Nasal Gel and placebo nasal gel will be administered twice daily over the six consecutive Treatment Days. The two daily doses of DPI-386 Nasal Gel or placebo nasal gel will be separated by a minimum of six hours ± 15 minutes, and will occur during the subject's on-duty period. The TDS patch will be administered on Treatment Days 1 and 4.

Inclusion Criteria:

1. Provision of signed and dated ICD.

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

3. Male or female, aged 18 to 59 (inclusive).

4. Active duty military or reserves on active status. All potential subjects must be able to provide a current military ID to be viewed by PI or qualified designee prior to signing the ICD.

5. At least minimally susceptible to provocative motion as evidenced by a minimum score of 3.0 on the Motion Sickness Susceptibility Questionnaire (MSSQ).

6. In good general health as evidenced by medical history with no recent history or current diagnosis of clinical problems as recommended by the PI or qualified designee.

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

8. For females of child-bearing potential: willingness to provide a urine sample for the hCG pregnancy test. Test must be negative.

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

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

Exclusion Criteria:

1. Pregnancy, lactation, or positive urine pregnancy test at screening.

2. Known allergic reactions to scopolamine or other anticholinergics.

3. Currently prescribed any of the following medication types: belladonna alkaloids, antihistamines (including meclizine), tricyclic antidepressants, and muscle relaxants.

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

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

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

7. Having any of the following medical conditions within the last two years or deemed clinically significant by the PI or qualified designee as being exclusionary:

   1. Significant gastrointestinal disorder, asthma, or seizure disorders.
   2. History of vestibular disorders.
   3. History of narrow-angle glaucoma.
   4. History of urinary retention problems.
   5. History of alcohol or drug abuse.
   6. Nasal, nasal sinus, or nasal mucosa surgery.