DPI 386 Nasal Gel for the Prevention of Nausea Associated With Motion Sickness

Study Overview
=================
Brief Summary
-----------------
Determine the efficacy, in terms of time to nausea (inclination to vomit), of DPI-386 Nasal Gel as compared to the current standard of care (TDS) and placebo nasal gel. • Describe the pharmacokinetics (PK) of a multi-dose schedule of DPI-386 Nasal Gel (0.2 mg twice a day for six consecutive days) as compared to the current standard of care (TDS). Determine the safety of a multi-dose schedule of DPI-386 Nasal Gel with an emphasis on cognitive adverse events as compared to the current standard of care (TDS) and placebo nasal gel. Determine how alertness is affected by administration of DPI-386 Nasal Gel, as compared to the current standard of care (TDS) and placebo nasal gel.

Detailed Description
-----------------
Each subject eligible for the study on Day 0 will be assigned a subject number (starting with 101 for male subjects and 201 for female subjects) in consecutive order which will randomize the subject to one of the three study arms: double-blind DPI-386 Nasal Gel; double-blind placebo nasal gel; or Transderm Scop® (TDS). The subject number will link the nasal gel (active or placebo) treatment arms (double-blind) to a multi digit random number (study drug kit number) different from the subject number. The nasal gel vials, contained in the study drug kit, will be labelled with the same study drug kit number. Each 0.12 gram of the gel contains 0.2 mg of scopolamine HBr as the active ingredient along with the excipients sodium citrate, citric acid, sodium metabisulfite, glycerin, benzalkonium chloride, polyvinyl alcohol, and purified water.

Official Title
-----------------
A Randomized, Double-Blind Placebo-Controlled Phase 3 Study of the Safety, Pharmacokinetics, and Efficacy of DPI 386 Nasal Gel for the Prevention of Nausea Associated With Motion Sickness

Conditions
-----------------
Motion Sickness

Intervention / Treatment
-----------------
* Drug: DPI-386 Nasal Gel
* Drug: DPI-386 Placebo Nasal Gel
* Drug: Transderm Scop®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated ICD. Stated willingness to comply with all study procedures and availability for the duration of the study. Male or female, aged 18 to 59 (inclusive). Active duty military, reserves on active status, or dependents covered by Tricare health insurance. All potential subjects must be able to provide a current military or DoD dependent ID to be viewed by the PI or qualified designee prior to signing the ICD. At least minimally susceptible to provocative motion as evidenced by a minimum score of 3.0 on the Motion Sickness Susceptibility Questionnaire (MSSQ). In good general health as evidenced by medical history with no recent history or current diagnosis of clinical problems that would affect rotation in a vestibular study (e.g., vestibular pathology, seizure disorder, sinus congestion), as assessed by the PI or qualified designee. Laboratory test results that are determined by the PI or qualified designee to be normal or - if slightly out of the normal range - determined to be not clinically significant. The following laboratory tests will be performed: Hematology panel (WBC, RBC, HGB, Hct) Biochemistry panel (liver function: bilirubin [total and direct], ALT, AST, ALP, and GGT; Albumin, Creatinine, BUN, and Cortisol) Electrolytes (Na+, K+, Cl-, Ca2+, and PO4) Ability to take intranasal medication and willingness to adhere to the study schedule and time constraints. For females of child-bearing potential: willingness to provide a urine sample for the hCG pregnancy test upon every visit to NAMRU-D. Test must be negative. Agreement to adhere to the following lifestyle considerations: 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. Caffeine intake limited to 900 mg per day (six 8-ounce cups per day [daily total of 1.4 liters]) during the six treatment days. Abstain from alcohol for 24 hours prior to first dose of study medication and during the six treatment days. Cigarettes limited to no more than one pack per day; cigars to one per day; and chewing tobacco to no more than a quarter of a can per day 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, muscle relaxants and nasal decongestants. 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. Use of a nicotine patch. 8. 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 vestibular disorders. History of narrow-angle glaucoma. History of urinary retention. History of alcohol or drug abuse. Nasal, nasal sinus, or nasal mucosa surgery.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The sample size of 54 allows for an equal distribution of subjects within gender and treatment arm: 18 subjects per treatment arm with 9 per gender.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPI-386 Nasal Gel<br>Active DPI-386 Nasal Gel | Drug: DPI-386 Nasal Gel<br>* Nasal gel<br>|
| Placebo Comparator: DPI-386 Placebo Nasal Gel<br>Placebo Nasal Gel | Drug: DPI-386 Placebo Nasal Gel<br>* DPI-386 Placebo Nasal Gel<br>|
| Active Comparator: Transderm Scop® (TDS)<br>FDA approved Transderm Scop® (TDS). | Drug: Transderm Scop®<br>* Transderm Scop®<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The length of time spent in mechanical rotation until nausea (inclination to vomit) is achieved, or 20 minutes have elapsed. |  | up to 20 minutes |