Nasal Gel for the Prevention and Treatment of Nausea Associated With Motion Sickness

Study Overview
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Brief Summary
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Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study 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.

Detailed Description
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This Phase 3 clinical trial is a randomized, double-blind, placebo-controlled study 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 three arms: DPI-386 nasal gel, placebo nasal gel, and TDS patch (1.5 mg/72 hours), the current standard of care for the treatment of motion sickness. The study will include 34 subjects per arm, for a total of 102 subjects (n=102). A double dummy design will be used to mask the treatment assignment. All subjects will receive both a patch and nasal gel randomized to one of the following three arms: DPI-386 Nasal Gel + placebo patch, placebo nasal gel + placebo patch, or placebo nasal gel + TDS patch. Treatment Day 1 will be conducted aboard an ocean-going vessel to obtain data in an operationally relevant real world environment immediately followed by Treatment Days 2 and 3 at a clinical site or one of its two satellite locations.

Official Title
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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

Conditions
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Motion Sickness

Intervention / Treatment
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* Drug: DPI-386 Nasal Gel
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of a signed and dated Informed Consent Form (ICF). Stated willingness to comply with all study procedures and availability for the duration of the study. Male or female, aged 18 to 59 (inclusive). At least two responses on the MSSQ must be Sometimes or Frequently. 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. 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. The test must be negative within seven days of the Treatment Day 1. 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: Pregnancy, lactation, or positive urine pregnancy test within seven days of Treatment Day 1. Known allergic reactions to scopolamine or other anticholinergics. 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) Hospitalization or significant surgery requiring hospital admittance within the past six months. Treatment with another investigational drug or other intervention within the past 30 days. Having donated blood or plasma or suffered significant blood loss within the past 30 days. 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.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DPI-386 Nasal Gel + placebo patch<br>DPI-386 Nasal Gel: Each 0.12 gram of the gel contains 0.2 mg of scopolamine HBr | Drug: DPI-386 Nasal Gel<br>* 1.5 mg reservoir of scopolamine to be delivered over a 72-hour period<br>* Other names: Transderm Scop®;Drug: Placebos<br>* Placebo Nasal Gel and placebo patch<br>|
| Placebo Comparator: Placebo nasal gel + Placebo patch<br>Placebo | Drug: Placebos<br>* Placebo Nasal Gel and placebo patch<br>|
| Active Comparator: placebo nasal gel + TDS patch<br>Transderm Scop® is a commercial transdermal scopolamine (TDS) patch worn behind the ear containing a 1.5 mg reservoir of scopolamine to be delivered over a 72-hour period. | Drug: DPI-386 Nasal Gel<br>* 1.5 mg reservoir of scopolamine to be delivered over a 72-hour period<br>* Other names: Transderm Scop®;Drug: Placebos<br>* Placebo Nasal Gel and placebo patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of subjects who developed motion sickness. | Number of Subjects who developed motion sickness | 8 hours | 
| Adverse Event (AE) Reporting of DPI-386 | Number of subjects with indicated AEs receiving DPI-386 | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of nausea as measured by the Visual Analog Scale (VAS) | VAS - Respondents specify their degree of nausea by indicating a point along a continuous 100 mm line between two end-points; left one is for No nausea and the right one for Very severe nausea. Scoring is based on the length from left point and a higher score means more severe degree of nausea (Spinks & Wasiak, 2011). | During the 8 hour voyage on Treatment Day 1. | 
| Severity of motion sickness as measured by the Motion Sickness Assessment Questionnaire (MSAQ) over the treatment period. | MSAQ - The MSAQ was designed to measure motion sickness as a multi-dimensional construct, with the understanding that when an individual states they are experiencing motion sickness, it is unlikely a single symptom, but rather a complex set of symptoms, with varying levels of severity. Sixteen symptoms are listed, with symptoms differentiated along four dimensions: gastrointestinal, central, peripheral, and sopite-related. Each symptom is scored from 1 to 9 in severity and scores then calculated. All 16 items were collected from the general public instead of experts, allowing for a more accurate wording of the symptomology experienced by persons outside of physiological sciences. The MSAQ has been repeatedly validated and is strongly correlated with both the Pensacola Diagnostic index (r = 0.81, p < 0.001) and the Nausea Profile (r = 0.92, p < 0.001). | During the 8 hour voyage on Treatment Day 1. | 
| 3. Cognition as measured by the Automated Neuropsychological Assessment Metrics (ANAM). | This battery consists of the ANAM CORE battery plus the Running Memory Continuous Performance Test (CPT). | During all three Treatment Days. | 
| Pharmacokinetic parameters of DPI-386 to be measured will include Maximum Observed Plasma Concentrations (Cmax) | Pharmacokinetics will be assessed by the amount of total free scopolamine at each time point blood is collected and plasma samples will be assayed for scopolamine using a fully validated LC/MS method. | On Treatment Days 2 -3, PK draws will occur at the following time points: -60, 30, 60, 90, 120, 180, 330, 390, 450, 480 and 600 minutes. | 
| Pharmacokinetic parameters of DPI-386 to be measured will include Time to Reach Maximum Observed Plasma Concentration (tmax). | Pharmacokinetics will be assessed by the amount of total free scopolamine at each time point blood is collected and plasma samples will be assayed for scopolamine using a fully validated LC/MS method. | On Treatment Days 2 -3, PK draws will occur at the following time points: -60, 30, 60, 90, 120, 180, 330, 390, 450, 480 and 600 minutes. | 
| Pharmacokinetic parameters of DPI-386 to be measured will include Area Under the Curve (AUC). | Pharmacokinetics will be assessed by the amount of total free scopolamine at each time point blood is collected and plasma samples will be assayed for scopolamine using a fully validated LC/MS method. | On Treatment Days 2 -3, PK draws will occur at the following time points: -60, 30, 60, 90, 120, 180, 330, 390, 450, 480 and 600 minutes. |