Pharmacokinetic and Efficacy Profile Intranasal Scopolamine Spray

• Sponsor: Repurposed Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02155309
• Collaborator: (none)
• Enrollment: 63
• Location: 1
• Arms: 2
• Duration (Months): 21
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Motion Sickness	Drug: Scopolamine; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetic and Efficacy Profile of Low-Dose Intranasal Scopolamine Spray for Motion Sickness
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Scopolamine 0.2 mg intranasal scopolamine, single dose	Drug: Scopolamine
Placebo Comparator: Placebo placebo intranasal (0.1 mg per nostril), single dose	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 59 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Naval Medical Research Unit	Dayton	Ohio	United States	45433

Sponsors and Collaborators

• Repurposed Therapeutics, Inc.

Investigators

• Principal Investigator: Willliam J Becker, Phd, Naval Medical Research Unit - Dayton

Study Documents (Full-Text)

None provided.

More Information

Publications

• Klöcker N, Hanschke W, Toussaint S, Verse T. Scopolamine nasal spray in motion sickness: a randomised, controlled, and crossover study for the comparison of two scopolamine nasal sprays with oral dimenhydrinate and placebo. Eur J Pharm Sci. 2001 May;13(2):227-32.

• Responsible Party: Repurposed Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02155309
• Other Study ID Numbers: NAMRUD.2013.0004
• First Posted: Jun 4, 2014
• Last Update Posted: Jan 17, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Repurposed Therapeutics, Inc.: scopolamine; motion; sickness
• Additional relevant MeSH terms: Motion Sickness; Scopolamine; Butylscopolammonium Bromide

Study Results

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 Detail	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.

Arm/Group Title	PK: Scopolamine Only, Open-label	Efficacy: Scopolamine, Then Placebo	Efficacy: Placebo, Then Scopolamine
Arm/Group Description	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.	Subjects received one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril) for the first of two Efficacy sessions, and then one dose of 0.2 mg placebo intranasal (0.1 mg per nostril) for the second Efficacy session. A minimum of one week separated the two sessions. Each session was identical except for contents of intranasal spray. 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.	Subjects received one dose of 0.2 mg intranasal placebo (0.1 mg per nostril) for the first of two Efficacy sessions, and then one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril) for the second Efficacy session. A minimum of one week separated the two sessions. Each session was identical except for contents of intranasal spray. 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.
Period Title: Overall Study
STARTED	13	10	13
COMPLETED	13	10	12
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	PK: Scopolamine Only, Open-label	Efficacy: All Study Participants (Crossover, Double-Blind)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	13	23	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	23 100%	36 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	30.31 (12.59)	30.96 (10.86)	30.72 (11.16)
Sex: Female, Male (Count of Participants)
Female	3 23.1%	5 21.7%	8 22.2%
Male	10 76.9%	17 73.9%	27 75%
Region of Enrollment (Count of Participants)
United States	13 100%	23 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Efficacy: Number of Head Movements During Rotation
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PK: Scopolamine Only, Open-label	Efficacy: Scopolamine and Placebo (Crossover, Double-blind)
Arm/Group Description	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.	Subjects received either one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril) or one dose of 0.2 mg placebo intranasal (0.1 mg per nostril) for two Efficacy sessions. Each session identical except for contents of intranasal spray. 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. One week minimum separated the two Efficacy sessions.
Measure Participants	0	22
Head Tilts: Scopolamine Condition	222.5 (105)
Head Tilts: Placebo Condition	191.7 (95.1)

Adverse Events

Arm/Group Title	PK: Scopolamine Only, Open-label		Efficacy: Scopolamine (Crossover, Double-blind)		Efficacy: Placebo (Crossover, Double-blind)
Arm/Group Description	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.		Subjects received either one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril) or one dose of 0.2 mg placebo intranasal (0.1 mg per nostril) for two Efficacy sessions. Each session identical except for contents of intranasal spray. 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. One week minimum separated the two Efficacy sessions.		Subjects received either one dose of 0.2 mg intranasal scopolamine (0.1 mg per nostril) or one dose of 0.2 mg placebo intranasal (0.1 mg per nostril) for two Efficacy sessions. Each session identical except for contents of intranasal spray. 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. One week minimum separated the two Efficacy sessions.
All Cause Mortality
	PK: Scopolamine Only, Open-label		Efficacy: Scopolamine (Crossover, Double-blind)		Efficacy: Placebo (Crossover, Double-blind)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/23 (0%)		0/23 (0%)
Serious Adverse Events
	PK: Scopolamine Only, Open-label		Efficacy: Scopolamine (Crossover, Double-blind)		Efficacy: Placebo (Crossover, Double-blind)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/23 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	PK: Scopolamine Only, Open-label		Efficacy: Scopolamine (Crossover, Double-blind)		Efficacy: Placebo (Crossover, Double-blind)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/13 (84.6%)		18/23 (78.3%)		19/23 (82.6%)
General disorders
Nonserious AEs	11/13 (84.6%)	42	18/23 (78.3%)	82	19/23 (82.6%)	65

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.