Evaluation of Dry Eye Symptoms in CAE With Application of Intranasal Neurostimulation

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02910713
• Collaborator: (none)
• Enrollment: 185
• Locations: 3
• Arms: 2
• Actual Duration (Months): 1
• Patients Per Site: 61.7
• Patients Per Site Per Month: 60.5

Study Details

Study Description

Brief Summary

This study evaluates the safety and effectiveness of the Intranasal Tear Neurostimulator applied intranasally (active) compared with the same device applied extranasally (control) relating to symptoms of dry eye exacerbated by the Controlled Adverse Environment model.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Device: Intranasal Tear Neurostimulator	N/A

Detailed Description

Participants will be randomized to a single application sequence, either sequence "A" (intranasal application followed by control application) or sequence "B" (control application followed by intranasal application) using the device. Upon entering the CAE, participants will complete dry eye questionnaires every five minutes and will administer the device either intranasally or extranasally in randomized sequence when a certain level of ocular discomfort has been reached.

Study Design

• Study Type: Interventional
• Actual Enrollment: 185 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Controlled, Single-Masked, Cross-Over Clinical Trial to Evaluate Dry Eye Symptoms With Application of the Oculeve Intranasal Tear Neurostimulator During Exposure to a Controlled Adverse Environment (CAE®)
• Actual Study Start Date: Sep 30, 2016
• Actual Primary Completion Date: Oct 31, 2016
• Actual Study Completion Date: Oct 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intranasal Application Intranasal Tear Neurostimulator applied intranasally device (active), intranasal application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.	Device: Intranasal Tear Neurostimulator; The device delivers small electrical currents, activating nerves that stimulate the body's natural tear production system.
Sham Comparator: Extranasal Application Intranasal Tear Neurostimulator device applied extranasally (control) for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.	Device: Intranasal Tear Neurostimulator; The device delivers small electrical currents, activating nerves that stimulate the body's natural tear production system.

Outcome Measures

Primary Outcome Measures

1. Change From Pre-Application to Post-Application in Eye Dryness Score (EDS) Using a Visual Analog Scale (VAS) [Pre-application to Post-application on Day 0]

   The participant rated their eye dryness (both eyes simultaneously) at all visits and every 5 minutes during CAE exposure by placing a vertical mark on the 100 mm horizontal line to indicate the level of eye dryness. 0 corresponds to "no dryness" and 100 corresponds to "maximal dryness". A negative change from Baseline indicates improvement. A cross-over linear model was used with symptom relief as the response variable; sequence, application location, period, and the application location by period interaction as fixed effects; and participant (sequence) as a random effect.

Secondary Outcome Measures

1. Change From Pre-Application to Post-Application in the Ora Calibra Ocular Discomfort Scale (ODS) Score [Pre-application to Post-application on Day 0]

   The participant graded their eye discomfort prior to CAE entry, during CAE exposure to threshold, then starting 1 minute after treatment application every 5 minutes in each eye separately using the Ora Calibra ODS where: 0=no discomfort to 4=constant discomfort. Data from the analysis eye was used to determine effectiveness. The analysis eye was defined as the eye that reached the threshold triggering the first application or if both eyes reach the threshold at the same time, the eye with the higher discomfort score or if both eyes are the same, the right eye was used. A negative change from Baseline indicates improvement. A cross-over linear model was used with symptom relief as the response variable; sequence, application location, period, and the application location by period interaction as fixed effects; and participant (sequence) as a random effect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Moderate to severe dry eye disease

• Normal lid/lash anatomy, blinking function and closure as determined by the Investigator

• Literate, able to speak English, and able to complete questionnaires independently

Exclusion Criteria:

• Chronic or recurrent epistaxis, coagulation disorders or other conditions that, in the opinion of the Investigator, may lead to risk of clinically significant increased bleeding

• Nasal or sinus surgery (including history of application of nasal cautery) or significant trauma to these areas

• Implanted metallic or electronic device in the head, a cardiac demand pacemaker, or an implanted defibrillator

• Corneal transplant in either or both eyes

• A woman who is pregnant, nursing an infant, or planning a pregnancy at the Screening Visit

• Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days prior to the Screening Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Eye Care Institute	Louisville	Kentucky	United States	40206
2	Total Eye Care, PA	Memphis	Tennessee	United States	38119
3	Nashville Vision Associates	Nashville	Tennessee	United States	37205

Sponsors and Collaborators

• Allergan

Investigators

• Study Chair: Michelle Senchyna, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT02910713
• Other Study ID Numbers: OCUN-011
• First Posted: Sep 22, 2016
• Last Update Posted: Jan 31, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca

Study Results

Participant Flow

Pre-assignment Detail	Intranasal and Extranasal data for this crossover study are combined because there is only access to combined arm data for this study. The study was acquired from another organization and limited results data are available.

Arm/Group Title	All Participants
Arm/Group Description	Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes at Day 0 when the participant experienced an Ocular Discomfort Score (ODS) ≥ 3 at 2 or more consecutive time points in at least one eye during controlled adverse environment (CAE) exposure; followed by Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during CAE exposure. Randomization determined the order of intranasal or extranasal application.
Period Title: Overall Study
STARTED	185
Safety Population: Entered CAE	171
COMPLETED	143
NOT COMPLETED	42

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes at Day 0 when the participant experienced an Ocular Discomfort Score (ODS) ≥ 3 at 2 or more consecutive time points in at least one eye during CAE exposure; followed by Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during CAE exposure. Randomization determined the order of intranasal or extranasal application.
Overall Participants	185
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (12.2)
Sex: Female, Male (Count of Participants)
Female	138 74.6%
Male	47 25.4%

Outcome Measures

1. Primary Outcome

Title	Change From Pre-Application to Post-Application in Eye Dryness Score (EDS) Using a Visual Analog Scale (VAS)
Description	The participant rated their eye dryness (both eyes simultaneously) at all visits and every 5 minutes during CAE exposure by placing a vertical mark on the 100 mm horizontal line to indicate the level of eye dryness. 0 corresponds to "no dryness" and 100 corresponds to "maximal dryness". A negative change from Baseline indicates improvement. A cross-over linear model was used with symptom relief as the response variable; sequence, application location, period, and the application location by period interaction as fixed effects; and participant (sequence) as a random effect.
Time Frame	Pre-application to Post-application on Day 0

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS) Population, all randomized participants who initiated a study application, who received both intranasal and extranasal applications.

Arm/Group Title	Intranasal Application	Extranasal Application
Arm/Group Description	Intranasal Tear Neurostimulator applied intranasally device (active), intranasal application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.	Intranasal Tear Neurostimulator device applied extranasally (control) for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.
Measure Participants	143	143
Least Squares Mean (Standard Error) [score on a scale]	-16.48 (1.692)	-3.12 (1.692)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intranasal Application, Extranasal Application
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided p-value for the difference between Intranasal and Extranasal.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-13.36
	Confidence Interval	(2-Sided) 95%; -17.31 to -9.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.999
	Estimation Comments

2. Secondary Outcome

Title	Change From Pre-Application to Post-Application in the Ora Calibra Ocular Discomfort Scale (ODS) Score
Description	The participant graded their eye discomfort prior to CAE entry, during CAE exposure to threshold, then starting 1 minute after treatment application every 5 minutes in each eye separately using the Ora Calibra ODS where: 0=no discomfort to 4=constant discomfort. Data from the analysis eye was used to determine effectiveness. The analysis eye was defined as the eye that reached the threshold triggering the first application or if both eyes reach the threshold at the same time, the eye with the higher discomfort score or if both eyes are the same, the right eye was used. A negative change from Baseline indicates improvement. A cross-over linear model was used with symptom relief as the response variable; sequence, application location, period, and the application location by period interaction as fixed effects; and participant (sequence) as a random effect.
Time Frame	Pre-application to Post-application on Day 0

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (FAS) Population, all randomized participants who initiated a study application, who received both intranasal and extranasal applications.

Arm/Group Title	Intranasal Application	Extranasal Application
Arm/Group Description	Intranasal Tear Neurostimulator applied intranasally device (active), intranasal application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.	Intranasal Tear Neurostimulator device applied extranasally (control) for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during the CAE exposure.
Measure Participants	143	143
Least Squares Mean (Standard Error) [score on a scale]	-0.93 (0.080)	-0.34 (0.080)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intranasal Application
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	One-sided p-value for the difference between Intranasal and Extranasal.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -0.80 to -0.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.101
	Estimation Comments

Adverse Events

Time Frame	Day 0
Adverse Event Reporting Description	Safety population included all randomized participants who entered the CAE. Intranasal and Extranasal Adverse Event (AEs) data for this crossover study are combined because there is only access to combined arm data for this study. The study was acquired from another organization and limited results data are available.
Arm/Group Title	All Participants
Arm/Group Description	Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes at Day 0 when the participant experienced an Ocular Discomfort Score (ODS) ≥ 3 at 2 or more consecutive time points in at least one eye during CAE exposure; followed by Intranasal Tear Neurostimulator device, intranasal or extranasal (control) application for approximately 3 minutes on Day 0 when the participant experienced an ODS ≥ 3 at 2 or more consecutive time points in at least one eye during CAE exposure. Randomization determined the order of intranasal or extranasal application.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	0/171 (0%)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/171 (0%)
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	0/171 (0%)

Limitations/Caveats

Intranasal and Extranasal data for this crossover study are combined because there is only access to combined arm data for this study. The study was acquired from another organization and limited results data are available.

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.