Motion Sickness
Conditions
Keywords
scopolamine, motion, sickness
Brief summary
Part 1, the pharmacokinetic (PK) phase, will expand upon the pilot study conducted at Naval Medical Research Laboratory (NAMRL) and has the goal of determining bioavailability and time to Cmax in a larger representative sample. Part 2, the efficacy phase, is to determine the efficacy of the aqueous spray solution via exposure to a nausea-inducing stimulus.
Detailed description
Part 1: The pharmacokinetic (PK) phase Objective: To determine the bioavailability and amount of scopolamine absorbed after administration of 0.2 mg intranasal scopolamine at regular intervals across 8 hours post- dose. Hypothesis: Detectable levels of Intranasal scopolamine (INSCOP) will be present in subject plasma within 15 minutes post-dose; mean time to Cmax (maximum plasma concentration) will be less than 1.5 hr. Part 2: The Efficacy phase Objective: To determine the effectiveness, cognitive performance effects, and medication side-effect profile of 0.2 mg intranasal scopolamine spray as a motion sickness (MS) countermeasure. Hypothesis: The primary hypothesis is that the INSCOP spray will be more efficacious against MS than placebo, without statistically significant cognitive performance side-effects. Specifically, participants will tolerate significantly more provocative head tilts in the INSCOP condition than in the placebo condition.
Interventions
DRUGScopolamine
DRUGPlacebo
Sponsors
Repurposed Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females, 18 to 59 years old, inclusive, in good general health as determined by physical examination and without clinically significant laboratory profiles * Normal weight for body size, based on Physical Readiness Test Body Composition Assessment (PPRTBCA) table * Willing and able to comply with study requirements and restrictions; and read and sign the informed consent.
Exclusion criteria
* Known and/or documented drug allergies, especially to scopolamine * Use of an investigational drug within 30 days of starting the study * Smoking or use of tobacco products, including chew or snuff, within six months * Blood donation or significant blood loss within 30 days of starting the study * Significant gastrointestinal disorder, asthma, or seizure disorders * History of narrow-angle glaucoma * History of urinary retention problems * History of alcohol or other drug abuse * Pregnancy or suspected pregnancy, or lactation * Hematocrit values less than 41% for males and 37% for females * Recent nasal, nasal sinus or nasal mucosa surgery * Use of prescription, over-the-counter, or herbal medication in past 7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Number of Head Movements During Rotation | 40 min | During rotation, efficacy is measured by the number of head movements subjects are able to make (12 per minute). While seated yaw-axis rotating, a pre-recorded computerized voice informed subjects to make paced head tilts of 30 ̊ to the right and left at a rate of 0.125 Hz (right, center, left, and back to center over 16 seconds). |
Countries
United States
Participant flow
Recruitment details
This study enrolled subjects who were active-duty military or reserves on active duty status between the ages of 18 and 59 from the Wright-Patterson Air Force Base located in Dayton, Ohio. The last subjects completed in August 2015.
Pre-assignment details
For the Pharmacokinetics part, 21 subjects were screened, and 13 completed the pharmacokinetics portion. For Efficacy, 42 subjects were screened, and 23 completed, with one removed from efficacy tabulated results due to noncompliance with study protocol. All subjects randomized into treatment order with cross-over design.
Participants by arm
| Arm | Count |
|---|---|
| PK: Scopolamine Only, Open-label Baseline vitals, blood draw, and cognitive testing applied. Subjects then received one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril). No placebo or efficacy. Blood draws, vitals collection, cognitive testing, and subjective fatigue collected for approximately eight hours post-dose. | 13 |
| Efficacy: All Study Participants (Crossover, Double-Blind) Double-blind, placebo-controlled, cross-over design. Study medications (0.2 mg of intranasal scopolamine and 0.2 mg of intranasal placebo) were randomized, blinded, and delivered in identical containers. Each subject participated in two sessions separated by minimum of one week, each session identical except for contents of intranasal spray. Order of treatment and placebo administration randomized. Baseline vitals, blood draw, and cognitive testing applied prior to dosage. Approximately 40 minutes post-dose, subjects experience mechanical rotation via Coriolis cross-coupling in a stairwise progression until subject reported either full minute of unabated stomach awareness, or the maximum rotation of 40 rpm obtained. Blood draws, vitals collection, cognitive testing and subjective fatigue collected for approximately three hours post-rotation. | 23 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Efficacy: All Study Participants (Crossover, Double-Blind) | PK: Scopolamine Only, Open-label | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 13 Participants | 36 Participants |
| Age, Continuous | 30.96 Years STANDARD_DEVIATION 10.86 | 30.31 Years STANDARD_DEVIATION 12.59 | 30.72 Years STANDARD_DEVIATION 11.16 |
| Region of Enrollment United States | 23 Participants | 13 Participants | 36 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 17 Participants | 10 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 11 / 13 | 18 / 23 | 19 / 23 |
| serious Total, serious adverse events | 0 / 13 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Efficacy: Number of Head Movements During Rotation
During rotation, efficacy is measured by the number of head movements subjects are able to make (12 per minute). While seated yaw-axis rotating, a pre-recorded computerized voice informed subjects to make paced head tilts of 30 ̊ to the right and left at a rate of 0.125 Hz (right, center, left, and back to center over 16 seconds).
Time frame: 40 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Efficacy: Scopolamine and Placebo (Crossover, Double-blind) | Efficacy: Number of Head Movements During Rotation | Head Tilts: Scopolamine Condition | 222.5 Number of head tilts | Standard Deviation 105 |
| Efficacy: Scopolamine and Placebo (Crossover, Double-blind) | Efficacy: Number of Head Movements During Rotation | Head Tilts: Placebo Condition | 191.7 Number of head tilts | Standard Deviation 95.1 |