Prospective, Open-Label, Randomized, Proof of Concept Study Exploring Application of TrueTear™ for the Treatment of Meibomian Gland Disease
Phase: NA
Conditions: Meibomian Glands, Dry Eye Syndromes
Sponsor: Allergan

NCT03226769 
 
Study ID: OCUN‐023 
 
 
 
Title:  Prospective, Open‐Label, Randomized, Proof of Concept Study Exploring Application of 
TrueTear™ for the Treatment of Meibomian Gland Disease 
 
Protocol Date: 01 Jun 2017 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 1 of 63 
01-JUN-2017   
 
 
ALLERGAN CONFIDENTIAL 
The following contains confidential, proprietary information 
which is the property of Allergan 
Prospective, Open-Label, Randomized, Proof of Concept Study Exploring 
Application of TrueTear™ for the Treatment of Meibomian Gland Disease 
 
Protocol Number: 
 
OCUN-023 
Original Protocol:  
June 1, 2017 
Device Name: 
TrueTear 
Sponsor: 
Allergan, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 2 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 3 of 63 
01-JUN-2017   
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 4 of 63 
01-JUN-2017   
SYNOPSIS 
Protocol Title: 
Prospective, Open-Label, Randomized, Proof of Concept 
Study Exploring Application of TrueTear™ for the 
Treatment of Meibomian Gland Disease 
Protocol Number: 
OCUN-023 
Study Device(s): 
TrueTear 
Study Objective: 
The primary objective of this study is to compare the safety 
and efficacy of TrueTear to standardized moist heat 
compress (Thermalon® Dry Eye Compress) for the 
treatment of Meibomian Gland Disease (MGD) 
Overall Study Design 
Structure: 
Prospective, open-label, randomized (1:1), parallel two arm 
design  
Duration: 
An individual participant’s participation is expected to last 
approximately 44 days 
Controls: 
Thermalon Dry Eye Compress 
 
 
Device Regimen: 
TrueTear: 
 Initial in-office application of approximately 8 minutes 
duration at Visit 2 
  
 Second in-office application of approximately 3 
minutes at Visit 3 
 
 Daily use of TrueTear per Patient Guide with 
assessments at Visit 3 (
, Visit 4 
 and 
Visit 5 (
   
Control Regimen: 
Thermalon Dry Eye Compress: 
 In-office applications at Visit 2 (
 and Visit 3 
 and daily use as per label instructions with 
assessments at Visit 3 
 Visit 4
 and 
Visit 5 (
   
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 5 of 63 
01-JUN-2017   
Study Population Characteristics 
Number of Participants: 
Approximately 70 participants (approximately 35 
participants per arm), will be enrolled at up to two sites in 
the US. 
Condition/Disease: 
Meibomian Gland Disease 
Evaluation Criteria 
 
 
  
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
General Statistical Methods and Types of Analyses 
 
Sample Size 
As this is a proof of concept study, no formal calculation of sample size was conducted. 
Approximately 70 participants will be enrolled to achieve approximately 60 completed 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 6 of 63 
01-JUN-2017   
participants. 
 
General Statistical Methods  
Statistical analyses will use a two-tailed test and will be evaluated at an α of 0.05 unless 
otherwise specified. The mean, standard deviation (SD), median, minimum and maximum will 
be presented for continuous variables such as participant age. For categorical variables, such as 
sex, the number for each category, the total number evaluated, and the percentage will be 
presented. 
 
 
 
 
 
 
 
 
 
 
 
. 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 7 of 63 
01-JUN-2017   
TABLE OF CONTENTS 
SYNOPSIS .................................................................................................................................4 
TABLE OF CONTENTS ...........................................................................................................7 
TABLE OF FIGURES ...............................................................................................................9 
LIST OF ABBREVIATIONS ..................................................................................................10 
1.0 INTRODUCTION ...........................................................................................................11 
1.1 
Background ............................................................................................................11 
1.2 
Rationale ................................................................................................................11 
2.0 STUDY OBJECTIVES ....................................................................................................12 
3.0 CLINICAL HYPOTHESES ............................................................................................12 
4.0 OVERALL STUDY DESIGN .........................................................................................12 
5.0 STUDY POPULATION ..................................................................................................14 
5.1 
Number of Participants ..........................................................................................14 
5.2 
Study Population Characteristics ...........................................................................14 
5.3 
Inclusion Criteria ...................................................................................................14 
5.4 
Exclusion Criteria ..................................................................................................15 
5.5 
Inclusion/Exclusion Exceptions .............................................................................17 
5.6 
Discontinuation Criteria (if applicable) .................................................................17 
 
 
 
 
 
 
7.0 DEVICE DESCRIPTION ................................................................................................19 
7.1 
TrueTear Investigational Device ............................................................................19 
7.2 
TrueTear Accountability ........................................................................................20 
7.3 
Control Description - Thermalon Dry Eye Compress ...........................................20 
7.4 
Other Study Supplies .............................................................................................21 
8.0 STUDY METHODS AND PROCEDURES ...................................................................21 
8.1 
Participant Entry Procedures..................................................................................21 
 
Overview ......................................................................................................21 
8.1.1
 
Informed Consent.........................................................................................21 
8.1.2
 
 
 
Procedures for Final Study Entry .................................................................22 
8.1.4
 
Methods for Assignment to Application Groups .........................................22 
8.1.5
8.2 
Masking..................................................................................................................23 
8.3 
Participant Training, Dispensing and Home Use of TrueTear ..............................23 
8.4 
Participant Training, Dispensing and Home Use of Thermalon Dry Eye Compress24 
8.5 
Concurrent Therapies .............................................................................................24 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 8 of 63 
01-JUN-2017   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.8 
Completed Participants ..........................................................................................29 
8.9 
Study Termination .................................................................................................29 
8.10 
Study Duration .......................................................................................................29 
8.11 
Monitoring and Quality Assurance ........................................................................29 
 
Study Monitoring .........................................................................................29 
8.11.1
 
Recording of Data ........................................................................................30 
8.11.2
9.0 ADVERSE EVENTS .......................................................................................................30 
9.1 
Adverse Event Recording ......................................................................................30 
9.2 
Adverse Event Evaluation......................................................................................30 
9.3 
Relationship of the AE to the investigational device .............................................31 
9.4 
Serious and Unanticipated Adverse Device Effects ..............................................31 
9.5 
Adverse Event Reporting .......................................................................................32 
9.6 
Anticipated Adverse Events ...................................................................................33 
10.0 PREGNANCY .................................................................................................................34 
11.0 STATISTICAL HYPOTHESIS AND METHODS OF ANALYSES .............................34 
11.1 
Power Calculation and Determination of Sample Size ..........................................34 
11.2 
Statistical Hypotheses and Level of Significance ..................................................34 
11.3 
Randomization .......................................................................................................35 
11.4 
GENERAL STATISTICAL CONSIDERATIONS ...............................................35 
11.5 
Participant Accountability and Missing Data ........................................................35 
11.6 
Participant Demographic and Baseline Characteristics .........................................35 
 
 
 
 
 
 
12.0 FINAL CLINICAL STUDY REPORT ...........................................................................36 
13.0 COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ...........................................36 
13.1 
Protection of Human Participants ..........................................................................36 
 Participant Informed Consent ................................................................................36 
13.1.1

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 9 of 63 
01-JUN-2017   
 Institutional Review Board (IRB) Approval ..........................................................36 
13.1.2
 Ethical Conduct of the Study .................................................................................36 
13.1.3
 Participant Confidentiality .....................................................................................36 
13.1.4
13.2 
Documentation .......................................................................................................37 
 
Retention of Documentation ........................................................................37 
13.2.1
13.3 
REGULATORY STATUS ....................................................................................37 
13.4 
Labeling, Packaging, Storage, Accountability, and Return or Disposal of Study 
Device ....................................................................................................................37 
13.5 
Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Thermalon Dry Eye Compresses ...........................................................................38 
13.6 
Recording of Data on Source Documents and Case Report Forms (CRFs) ..........38 
13.7 
Amendments to the Protocol ..................................................................................38 
13.8 
Publications ............................................................................................................38 
14.0 REFERENCES ................................................................................................................38 
15.0 APPENDICES .................................................................................................................40 
15.1 
Appendix 1: Schedule of Visits and Measurements ..............................................41 
15.2 
Appendix 2: Examination Procedures, Tests, Equipment, and Techniques ..........43 
 
Visual Acuity Procedures ............................................................................43 
15.2.1
 
Slit Lamp Biomicroscopy ............................................................................44 
15.2.2
 
Tear Film Breakup Time Evaluated .............................................................44 
15.2.3
 
Corneal and Conjunctival Sodium Fluorescein Staining .............................45 
15.2.4
 
Three-Minute Schirmer Test with Topical Anesthesia ................................46 
15.2.5
 
Symptom Questionnaires .............................................................................48 
15.2.6
15.2.6   Tearscope .....................................................................................................58 
 
Lower Lid Assessment and Photography ....................................................58 
15.2.7
 
Lower Lid Meibography with LipiScan ......................................................59 
15.2.8
 
Lower Lid Margin Meibomian Gland Expression .......................................60 
15.2.9
 Thermal Video Acquisition (FLIR) .............................................................61 
15.2.10
 Intranasal Examination ................................................................................61 
15.2.11
15.3 
Appendix 3: Sponsor and 
 Approvals ..............................................................62 
15.4 
Appendix 4: Investigator’s Signature ....................................................................63 
 
TABLE OF FIGURES 
Figure 1 
The TrueTear System Components ............................................................................ 20 
Figure 2 
Use of TrueTear .......................................................................................................... 24 
  
 
 
 
  
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 10 of 63 
01-JUN-2017   
 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
ADE 
Adverse device effect 
CDVA 
Corrected distance visual acuity 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CN 
Cranial nerve 
DED 
Dry eye disease 
DHHS 
Department of Health and Human Services 
CRF 
Case report form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FDA 
Food and Drug Administration 
GCP 
Good clinical practice 
HIPAA 
Health Information Portability and Accountability Act 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IPL 
Intense pulsed light 
IRB 
Institutional/independent review board 
LASEK 
Laser-assisted sub-epithelial keratectomy 
LASIK 
Laser-assisted in-situ keratomileusis 
LED 
Light-emitting diode 
LFU 
Lacrimal functional unit 
LLT 
Lipid layer thickness 
logMAR 
Logarithm of the minimum angle of resolution 
MGD 
Meibomian gland disease 
Mm 
Millimeter 
 
 
OTC 
Over-the-counter 
PP 
Per protocol 
PRK 
Photorefractive keratectomy 
SAE 
Serious adverse event 
SD 
Standard deviation 
 
  
TBUT 
Tear film breakup time 
TENS 
Transcutaneous electrical nerve stimulation 
US 
United States 
WOCBP 
Women of childbearing potential 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 11 of 63 
01-JUN-2017   
1.0 INTRODUCTION 
1.1 
Background 
Meibomian gland disease (MGD) is a chronic, diffuse abnormality of the meibomian glands, 
commonly characterized by terminal duct obstruction and/or qualitative/quantitative changes in 
glandular secretion.1 MGD is a common eyelid disorder that has widespread prevalence of 37% 
to 47% in the United States (US) alone.2 The incidence of MGD has been found to increase with 
age3-9 and is markedly higher in Asian populations (46.2% to 69.3%).10-12 MGD may result in 
alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and 
ocular surface disease.13 Combined, these manifestations afflict millions of people worldwide, 
with more than 10 million in the US alone.2,13  
Current recommendations for the management and treatment of MGD include: 1) lid-heating, 
massage, and cleaning, 2) topical antibiotic and/or topical steroids, 3) systemic anti-
inflammatory antibiotics (e.g., tetracycline), 4) lubricants as adjunctive treatment, 5) LipiFlow® 
Thermal Pulsation System, 6) meibomian gland probing and 7) meibomian gland expression.  
Lid warming, lid hygiene, and lubricants are often found to be suboptimal / only partially 
effective.2 Meibomian gland probing and expression can lead to patient discomfort and/or 
damage to the lid margin. Topical antibiotic and/or an antibiotic-steroid combination are 
prescribed for acute exacerbated cases or for anterior blepharitis, but are short-term and may not 
address the underlying cause(s) of MGD. Systemic antibiotics may lead to systemic side effects 
including gastrointestinal disturbance (e.g., from tetracyclines). Therefore, there remains a need 
for new treatment strategies targeting the treatment of MGD. 
1.2 
Rationale 
The nasolacrimal reflex is a well-established pathway by which nasal stimuli promote both 
resting basal14 and bolus tear secretion. The reflex plays a functional role in expelling foreign 
bodies or irritants from the nose by secreting tears into the nasal cavity via the nasolacrimal duct 
upon stimulation by the irritant.   
Reflex activation of the lacrimal glands is also one of the body’s primary compensatory 
mechanisms for addressing ocular surface dryness. Unfortunately, over time, an arid 
environment and resulting inflammation results in damage to the afferent nerves innervating the 
cornea, compromising the reflex response and ultimately leading to an even drier ocular surface. 
Studies have demonstrated that intranasal stimulation via use of the TrueTear application results 
in a statistically significant increase in tear production measured by the Schirmer test.15,16 To 
date, however, little is known regarding the role intranasal neurostimulation may have on 
secretion of meibum. The meibomian glands are not innervated directly17 and the mechanism by 
which meibum that is secreted into the glands and expressed onto the eyelids is a two-stage 
process. First meibum is continually secreted by sebaceous cells into the meibomian glands for 
storage prior to expression.18,19 Second, meibum expression is achieved though coordinated 
muscular activity (which can be initiated by numerous stimuli such as blinking), of the 
orbicularis muscle (the eyelid) contracting, and Riolan’s muscle (a sphincter at the orifice of the 
glands just below the lid margin) relaxing. The innervation to the musculi orbicularis and 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 12 of 63 
01-JUN-2017   
Riolan’s is provided by the facial nerve (cranial nerve CN-VII) whose fibers transmit action 
potentials to contract said musculi upon neural activity in the superior salivatory nucleus in the 
brainstem.18,20 This nucleus is responsible for the secretion of tears and tear components and 
shows neural activity when sensory nerve endings of the anterior ethmoidal nerve, a sub-branch 
of the trigeminal nerve, are stimulated.21-23 The TrueTear stimulates the anterior ethmoidal nerve 
inside the nose, thereby increasing neural activity in the superior salivary nucleus, which in turn 
drives action potentials on the facial nerve to the lacrimal gland as well as provides the signals 
for coordinated activation of the orbicularis and the Riolan’s muscles, thereby expressing 
meibum from the meibomian glands. As such, there is reason to believe that meibum expression 
may be achieved following stimulation of anterior ethmoidal afferences inside the nose.  
A clinical study conducted by the Sponsor measuring meibomian gland activity and tear film 
lipid layer thickness stimulated with use of TrueTear supports this assumption. Specifically, in 
this study, evidence of increased meibomian gland secretion activity and increased tear film lipid 
layer thickness was measured following a single use of TrueTear relative to both pre-application 
of TrueTear and an extranasal control.24 It is thus of interest to the Sponsor to investigate the 
effectiveness of TrueTear as a potential novel treatment strategy for MGD. 
 
2.0 STUDY OBJECTIVES 
The primary objective of this study is to compare the safety and efficacy of TrueTear (intranasal 
tear neurostimulation) to standardized moist heat compress (Thermalon Dry Eye Compress) for 
the treatment of Meibomian Gland Disease (MGD). 
3.0 CLINICAL HYPOTHESES 
Thirty days of TrueTear application provides efficacious treatment of MGD compared to moist 
heat compress control as measured by signs and/or symptoms of MGD.   
4.0 OVERALL STUDY DESIGN 
This is a prospective, randomized, parallel two-arm study conducted at up to two sites, designed 
to characterize the effectiveness of TrueTear on the signs and symptoms of MGD. 
Approximately 70 male and female participants at least 22 years of age with a participant-
reported history of dry eye or MGD and meeting all other study eligibility criteria will be 
randomized in a 1:1 ratio to either the TrueTear or moist heat compress control treatment groups. 
Following the initial application of treatment in clinic at Day 0, participants will apply the 
randomized treatment for approximately 30 days. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 13 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 14 of 63 
01-JUN-2017   
 
5.0 STUDY POPULATION 
5.1 
Number of Participants 
It is estimated that approximately 70 participants will be enrolled at up to two sites in the 
US to complete approximately 60 participants. 
Participants will be randomized in a 1:1 ratio to one of two possible treatment groups:  
 
TrueTear  
 
Thermalon Dry Eye Compress (moist heat compress)  
5.2 
Study Population Characteristics  
All participants should meet all inclusion criteria and none of the exclusion criteria. 
 
5.3 
Inclusion Criteria 
Participants should: 
1. Be twenty-two (22) years of age or older at the Screening Visit 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 15 of 63 
01-JUN-2017   
2. At the Screening and Baseline Visits, have a Standard Patient Evaluation for Dryness 
(SPEED) 
 
3. In at least one eye, meet all of the following objective measures in the same eye: 
 
A basal Schirmer test 
 
  
 
 
 
 
 
 
 
Tear film breakup time (TBUT) ≥
 
 
4. Have used an artificial tear product, lid hygiene 
 
; omega-3 supplementation; antibiotics 
 
 
 for the treatment of dry eye disease or meibomian gland 
disease within one year of the Screening Visit 
 
 
 
 
 
 
 
5.4 
Exclusion Criteria 
Participants should not: 
1. Have chronic or recurrent epistaxis, coagulation disorders or other conditions that, in the 
opinion of the Investigator, may lead to clinically significant risk of increased bleeding 
2. Have had nasal or sinus surgery (including history of application of nasal cautery) or 
significant trauma to these areas  
3. Have a vascularized polyp, severely deviated septum or severe nasal airway obstruction 
as confirmed by intranasal examination performed at the Screening Visit 
4. Have had any intraocular surgery (such as cataract surgery), extraocular surgery (
 
) in either eye within three months of the Screening Visit or refractive 
surgery 
 within twelve months of the 
Screening Visit 
 
 
 
 
  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 16 of 63 
01-JUN-2017   
16. Have a cardiac demand pacemaker, implanted defibrillator, or other active implanted 
metallic or active implanted electronic device in the head  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 17 of 63 
01-JUN-2017   
 
  
 
 
 
 
   
 
    
 
 
 
 
5.5 
Inclusion/Exclusion Exceptions 
The Investigator has the right to exclude a potential participant’s enrollment in the study if s/he 
deems it in the best interest of the participant. Reasons for exclusion on this basis will be 
recorded.   
5.6 
Discontinuation Criteria (if applicable) 
Participants are free to discontinue their participation in this study at any time and for any 
reason, specified or unspecified, without prejudice. In addition, the Investigator may decide to 
discontinue a participant from the study for safety reasons or when it is in the best interest of the 
participant. No constraints will be placed on ordinary patient management.  
Reasons for participant withdrawal may include but are not limited to the following: 
 
Either at the Investigator's request, for safety reasons (e.g., serious or severe AE), or 
at the participant’s request 
 
Non-compliance (e.g., failure to follow application instructions, missing visits, 
using prohibited medications) 
 
When a concomitant therapy likely to interfere with the results of the study is 
reported or required by the participant; the Investigator will report all such 
information on the source documents/case report forms (CRFs) and decide, in 
conjunction with the Sponsor, whether the participant is to be withdrawn 
 
Sound medical reason 
 
A confirmed positive pregnancy test at any time during the study 
 
When a participant is lost to follow-up. The Investigator (or designee) will make 
repeated attempts to reach the participant by telephone, email and/or letter before 
considering the participant as lost to follow-up. These actions will be documented 
and recorded on the End of Study CRF. Copies of follow-up letters, if any, should 
be maintained in the Investigator's file. 
 
When a participant is erroneously admitted into the study or does not meet the 
eligibility criteria 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 18 of 63 
01-JUN-2017   
In addition, the Sponsor also reserves the right to discontinue the study at any time for clinical or 
administrative reasons. 
All early discontinuations and their reasons should be carefully documented by the Investigator 
on the End of Study CRF and, if applicable, on the Adverse Event (AE) CRF. Notification of a 
participant’s discontinuation and the reason for discontinuation will be made to
 and/or 
Sponsor. No participant who has been randomized can be replaced by another participant if the 
participant is discontinued prematurely for any reason. 
6.0 STUDY PARAMETERS 
 
 
 
  
 
   
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

&OLQLFDO7ULDO3URWRFRO2&81

6SRQVRU$OOHUJDQ,QF
9HUVLRQ
&RQILGHQWLDO 
3DJHRI
-81  
 '(9,&('(6&5,37,21

7UXH7HDU,QYHVWLJDWLRQDO'HYLFH 
7KH7UXH7HDUGHYLFHGHOLYHUVVPDOOHOHFWULFDOFXUUHQWVWRWKHLQQHUFDYLW\RIWKHQRVHDFWLYDWLQJ
QHUYHVWKDWVWLPXODWHWKHERG\¶VQDWXUDOWHDUSURGXFWLRQV\VWHP
7KHGHYLFHFRQVLVWVRIIRXUGLVWLQFWSDUWV)LJXUH
 $UHXVDEOH%DVH8QLWZKLFKSURGXFHVWKHHOHFWULFDOVWLPXODWLRQZDYHIRUP
 $GLVSRVDEOH7LSWKDWLQVHUWVLQWRWKHQDVDOFDYLW\DQGVWLPXODWHVWKHWDUJHWLQWUDQDVDO
WLVVXH
 $UHXVDEOH&RYHUWRSURWHFWWKH7LS 
 $&KDUJHUZKLFKUHFKDUJHVWKHEDWWHU\LQVLGHWKH%DVH8QLW






%DVH8QLWZLWK'LVSRVDEOH7LSV)URQWDQG%DFN
%DVH8QLWZLWK&RYHU
7UXH7HDU6\VWHP

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 20 of 63 
01-JUN-2017   
 
Figure 1 
The TrueTear System Components 
 
 
Base Unit 
7.1.1
When activated, the Base Unit provides electrical pulses to the Tip. The strength of these pulses 
is controlled by two buttons, with five different intensity levels available, indicated by the 
number of illuminated LEDs on the Base Unit. The device internally records the time and 
duration of device use.   
 
Disposable Tip  
7.1.2
The disposable Tip is specially designed to allow the participant to easily apply stimulation to 
the target areas within the nose. The Tip attaches to the Base Unit and contains hydrogel (similar 
to the material used in contact lenses) that contacts the inside of the nose to provide stimulation. 
Each tip may be used up to 24 hours. After 24 hours, the used tip should be discarded and a fresh 
tip should be attached. A separate Cover can be used to protect the Tip and Base Unit when the 
device is not in use. 
 
Cover 
7.1.3
The Cover may be placed over the top of the Tip attached to the Base Unit for protection in 
between uses. 
 
Charger 
7.1.4
The Base Unit may be recharged by removing the Tip and placing the Base Unit onto the 
Charger. Charging typically takes under 4 hours, and a green LED indicates that the process has 
completed. 
  
7.2 
TrueTear Accountability 
Each Base Unit and Charger have unique serial numbers. The serial numbers of the Base 
Unit/Charger used by each participant will be recorded on the appropriate case report form and 
device accountability log. The disposable Tip is provided in a sealed pouch, which is labeled 
with a lot number and expiration date. The lot number of the Tips provided to the participant will 
also be recorded on the appropriate case report forms and on the device accountability log. Tips 
should not be used beyond the expiration date provided on the pouch.   
7.3 
Control Description - Thermalon Dry Eye Compress 
As described on the label, the Thermalon Dry Eye Compress
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 21 of 63 
01-JUN-2017   
 
.   
7.4 
Other Study Supplies 
The following will be provided by the Investigator: 
 Urine pregnancy test kits 
 Schirmer test strips 
 Weck-Cel eye spears 
 Proparacaine 
 Liquid sodium fluorescein 
 Calibrated 1-10 µL pipette and sterile pipette tips 
 
8.0 STUDY METHODS AND PROCEDURES 
8.1 
Participant Entry Procedures 
 
Overview 
8.1.1
Participants as defined by the criteria in section 5.2, 5.3, and 5.4 will be considered for entry 
into this study. 
 
Informed Consent 
8.1.2
Prior to a participant’s participation in the trial (i.e., prior to study-related procedures), the 
study will be discussed with each potential participant and participants wishing to 
participate should give written informed consent using an IRB approved informed consent 
form (ICF). The ICF should be the most recent version that has received approval by a 
properly constituted IRB. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 22 of 63 
01-JUN-2017   
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Procedures for Final Study Entry 
8.1.4
Participants should meet all inclusion and none of the exclusion criteria. 
 
Methods for Assignment to Application Groups 
8.1.5
At the Screening Visit, participants who provide written informed consent will be assigned a 
unique 5-digit screening number, 
. Screening 
numbers should be assigned in ascending consecutive order. Participants who meet all of the 
eligibility criteria will be scheduled to return for Visit 2 (Day 0).   
At Visit 2 (Day 0), participants who meet all eligibility criteria will be randomized to one of 
two treatment groups (TrueTear or Thermalon Dry Eye Compress control) in a 1:1 ratio. At 
Visit 2 (Day 0), participants will be randomized in sequential order. The randomization 
number will be recorded on the CRF/source document.  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 23 of 63 
01-JUN-2017   
8.2 
Masking  
Because the two devices are dissimilar and administered in very different ways, it will not be 
possible to mask the participant or the Investigator to the intervention assignment. As a means of 
minimizing bias where feasible, de-identified videos from the Tearscope assessment (lipid layer 
thickness) will be graded using the Guillon scale in a masked fashion. 
8.3 
Participant Training, Dispensing and Home Use of TrueTear 
At Visit 2 (Day 0), participants randomized to the TrueTear application group will be provided a 
TrueTear device and disposable tips to take home with them and use daily. Participants will be 
instructed to use the device as described in the Patient Guide. They will receive training to 
perform intranasal neurostimulation and will receive a copy of the Patient Guide. 
For the device application, participants will be told to turn on the unit by holding down the + 
button for approximately two seconds. There are five stimulation intensity levels and participants 
may adjust the level by pressing the + or – buttons to obtain a gentle tingling sensation. They 
will be instructed to fully insert the tips of the TrueTear into both nostrils simultaneously 
towards the top and front of the nose (as in Figure 2). Participants will be told they can cease 
stimulation by holding down the – button for approximately two seconds on the base unit or by 
withdrawing the tips from the nostrils. Participants will be instructed to replace the Tips with a 
new one if they do not feel any sensation.   
For the initial in-office device application at Visit 2 (Day 0), each participant will be told that the 
application will take place for approximately eight minutes and that the entire procedure will 
occur while the participant is seated and positioned in a slit lamp to allow for simultaneous 
viewing of meibomian gland activity in the lower lid and for collection of lid and tear film 
temperature data.  
At Visit 3 (Day 7), prior to in-office application and evaluation of tear secretion, trained clinical 
personnel will review procedures for the proper use of the device (e.g., correct positioning 
intranasally, frequency and duration of use, daily replacement and disposal of tips, etc.) with 
participants. As the device internally records the frequency and duration of device use, study 
staff may review this information with participants. Participants will be told that the in-office 
application of TrueTear at this visit should last for approximately three minutes.  
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 24 of 63 
01-JUN-2017   
 
 
Figure 2 
Use of TrueTear 
          (L) Starting position and (R) Correct application position by inserting the 
disposable tips fully into the nasal cavity and to the front of the nose.  
 
Note: Sponsor representatives may be present at visits to assist in training participants on the use 
of the device. 
 
8.4 
Participant Training, Dispensing and Home Use of Thermalon Dry Eye 
Compress 
At Visit 2 (Day 0), participants randomized to the Thermalon Dry Eye Compress application 
group will be provided a Thermalon Dry Eye Compress device to take home with them and use 
daily. Participants will be trained to follow the instructions for proper use and storage as 
described on the package insert or 
The following additional points will be 
noted:  
 Between study visits, participants will be asked to use the moist heat compress daily as 
described on the package insert 
 
 If participants wish to wash their compress, instructions can be found on the package insert 
or
 
 Participants will be reminded to fill out a diary to record daily use of the moist heat compress 
throughout the study duration. 
 Participants will be asked to return the moist heat compress at the end of the study.  
8.5 
Concurrent Therapies 
The use of any concurrent medication, prescription or OTC, is to be recorded on the participant’s 
CRF along with the reason the medication was taken. Concomitant medications that are 
considered necessary for the participant’s welfare, but will not interfere with study assessments 
and evaluations, will be allowed during the study at the Investigator’s discretion. 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 25 of 63 
01-JUN-2017   
Concurrent enrollment in another investigational drug or device study is not permitted. 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 26 of 63 
01-JUN-2017   
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
   
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 27 of 63 
01-JUN-2017   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 28 of 63 
01-JUN-2017   
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 29 of 63 
01-JUN-2017   
 
 
 
 
 
 
 
 
 
 
 
 
 
8.8 
Completed Participants 
A completed participant is one who has not been discontinued from the study and has 
successfully completed Day 30. 
8.9 
Study Termination 
The study may be stopped at any time by the Investigator, the Sponsor, and/or 
with 
appropriate notification. 
8.10 
Study Duration 
An individual participant’s participation will involve up to five visits over approximately a 44 
day period. 
8.11 
Monitoring and Quality Assurance 
 
Study Monitoring 
8.11.1
Allergan personnel (or designees) will monitor this study in a manner consistent with 
applicable health authority regulations and the procedures adopted by the SOPs of Allergan. 
Prior to the start of the study, member(s) of 
 (or designees) will review the protocol, 
CRFs, regulatory obligations, and other material or equipment relevant to the conduct of the 
study with the Principal Investigator/Sub-Investigator(s) and pertinent study staff. 
Monitoring visits will occur as necessary during the course of the investigation to verify: 
 
The rights and well-being of participants are protected 
 
The conduct of the investigation is in compliance with the currently approved 
protocol/amendment, GCP and IRB/IEC requirements 
 
The integrity of the data 
 
Study device accountability  

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 30 of 63 
01-JUN-2017   
 
Adequate study documentation 
During the course of the study, if the Sponsor (or designee) determines that the Investigator 
is non-compliant with the study plan and/or applicable regulatory requirements, the Sponsor 
(or designee) will take written action to correct the non-compliance and to secure 
compliance. In addition, the Sponsor (or designee) may terminate the Investigator’s 
participation in the study if appropriate, or if the Investigator remains non-compliant despite 
the Sponsor’s actions. This termination will be documented in a memo or follow-up letter to 
the Principal Investigator. 
 
Recording of Data  
8.11.2
Participant data recorded on CRFs during the study will be documented in an anonymous 
fashion. The participant will only be identified by the participant number. If, as an 
exception, it is necessary for safety or regulatory reasons to identify the participant, the 
Sponsor or its representatives, and the Investigator, are bound to keep this information 
confidential. 
 
9.0 ADVERSE EVENTS  
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory 
finding) symptom, or disease temporally associated with the use of an investigational product but 
not necessarily related to the investigational product. An AE may also be called a complication. 
The capture of AEs will begin with the participant’s entry into the study. 
9.1 
Adverse Event Recording 
All AEs spontaneously reported by the participant and/or in response to an open question from 
study personnel or revealed by observation, physical examination or other diagnostic procedures 
will be recorded on the appropriate pages of the CRF. Any clinically relevant deterioration in 
clinical finding is considered an AE and should be recorded. When possible, signs and symptoms 
indicating a common underlying pathology should be noted as one comprehensive event. 
9.2 
Adverse Event Evaluation 
The Investigator should evaluate if each AE is serious, related to the applicable study device and 
anticipated using the following definitions. 
A serious adverse event (SAE) is defined as any untoward medical occurrence that: 
 
It results in death (i.e., the AE actually causes or leads to death); 
 
It is life threatening (i.e., the AE places the participant at immediate risk of death); 
 
It requires or prolongs inpatient hospitalization. If a participant is hospitalized to 
undergo a medical or surgical procedure as a result of an AE, the event responsible 
for the procedure, not the procedure itself, should be recorded as the event.  For 
example, if a participant is hospitalized to undergo coronary bypass surgery, the 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 31 of 63 
01-JUN-2017   
heart condition that necessitated the bypass should be recorded. Hospitalizations for 
diagnostic or elective surgical procedures or hospitalizations required to allow 
outcome measurement for the study should not be recorded as SAEs: 
 
It results in persistent or significant disability/incapacity (i.e., the AE results in 
substantial disruption of the participant’s ability to conduct normal life functions); 
 
It results in a congenital anomaly/birth defect in a neonate/infant born to a mother 
exposed to the investigational device; 
 
It is considered a significant medical event by the Investigator based on medical 
judgment (e.g. may jeopardize the participant or may require medical/surgical 
intervention to prevent one of the outcomes listed above); 
 
It is considered sight-threatening by the Investigator. 
9.3 
Relationship of the AE to the investigational device 
Definite 
A clear-cut causal relationship with the study device 
and no other possible cause 
Probable 
A causal relationship with the study device is likely 
although alternate etiologies are also possible  
Possible 
A causal relationship with study device is not 
definite, alternate etiologies are also possible 
Not related 
The AE has no causal relationship to study device 
and/or there is evidence of alternative etiology such 
as concurrent medication or illness. 
Not 
applicable 
The participant has not been exposed to the study 
device. 
The AE will be determined to be device related, making it an adverse device effect (ADE), if it is 
identified to have had a definite, probable or possible causal relationship to the study device. 
An AE is unanticipated if the nature, severity, or frequency of the event is not consistent with 
either the known or foreseeable risk of AEs associated with the procedures involved in the 
research that are described in (a) the protocol-related documents, such as the IRB-approved 
research protocol, user manuals and the current IRB-approved informed consent document, and 
(b) other relevant sources of information such as product labeling and package inserts; or the 
expected natural progression of any underlying disease, disorder, or condition of the 
participant(s) experiencing the AE and the participant’s predisposing risk factor profile for the 
AE. 
9.4 
Serious and Unanticipated Adverse Device Effects 
A serious and unanticipated adverse device effect is defined as “any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device 
if that effect, problem, or death was not previously identified in nature, severity, or degree of 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 32 of 63 
01-JUN-2017   
incidence in the investigational plan, or any other unanticipated serious problem associated with 
a device that relates to the rights, safety or welfare of participants.” 
9.5 
Adverse Event Reporting 
All AEs that occur during the course of the study should be reported on the Adverse Event CRF. 
The Investigator should determine the intensity of the event. 
Mild 
Awareness of sign or symptom, but easily tolerated  
Moderate 
Discomfort enough to cause interference with 
normal daily activities  
Severe 
Inability to perform normal daily activities 
All SAEs and adverse device effects (ADEs) should be reported by the Investigator to 
 
and the Sponsor in writing within 24 hours from the point in time when the Investigator becomes 
aware of the event.  
It is the responsibility of the Investigator to promptly notify the Institutional Review Board (IRB) 
of all unanticipated SAEs and unanticipated problems, per the IRBs reporting requirements.  
Throughout the course of the proposed study, all efforts will be made to remain alert to possible 
adverse experiences or untoward findings. If adverse experiences occur, the first concern will be 
the safety and welfare of the participant. Appropriate medical intervention will be made.   
 and the Sponsor will immediately conduct an evaluation of any unanticipated adverse 
device effect. The results of the evaluation will be reported to the IRB within 10 days of
 
. and/or the Sponsor becoming aware of the event. If it is determined by 
 and the 
Sponsor to present an unreasonable risk to study participants, all investigations or parts of the 
investigation presenting that risk will be terminated as soon as possible. Termination will occur 
not later than five working days after 
. and the Sponsor makes this determination, and 
not later than 15 working days after first receiving notice of the event. 
 and the Sponsor 
will not resume an investigation terminated under these conditions without an additional IRB 
approval.  
Contact information for reporting Serious Adverse Events: 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 33 of 63 
01-JUN-2017   
  
9.6 
Anticipated Adverse Events  
The following is a list of potential AEs associated with the use of the device:  
 
Nasal discomfort or pain 
 
Epistaxis 
 
Excessive sneezing    
 
Nasal irritation, paresthesia or numbness post-stimulation 
 
Nasal infection, abrasion or inflammation 
 
Skin irritation or hypersensitivity 
 
Headache (e.g., tension, migraine, etc.)  
 
Facial pain 
 
Excessive salivation 
 
Sensation of teeth vibrating 
 
Excessive rhinorrhea 
 
Temporary aggravation of nasal allergies 
 
Allergic reaction to contact materials 
 
As described on the Thermalon Dry Eye Compress label, the following potential AE associated 
with the use of Thermalon Dry Eye Compress may occur: 
 
Blurry vision 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 34 of 63 
01-JUN-2017   
10.0 PREGNANCY 
Women of Childbearing Potential (WOCBP) include any females who have experienced 
menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral 
tubal ligation or bilateral oophorectomy) or are not postmenopausal at least 12 months since last 
menses. WOCBP will be required to use designated methods of birth control during the course of 
the study such as abstinence, sterile male partner, oral contraceptive pills, contraceptive patches, 
injectable contraception, vaginal rings, intrauterine contraception, or barrier methods. All women 
who are pregnant, nursing an infant, or planning a pregnancy during the duration of this study 
will be excluded from participation.  
If a participant or Investigator suspects that the participant may be pregnant prior to study device 
administration, the study device should be withheld until the results of pregnancy testing are 
available. If pregnancy is confirmed, the participant should not administer the study device and 
should not be enrolled in the study. 
If a female participant becomes pregnant during the study, the Investigator will notify Allergan 
immediately after the pregnancy is confirmed. The Investigator will (1) obtain a consent from the 
female participant for pregnancy follow-up and (2) follow the progress of the pregnancy to term. 
The Investigator must document the outcome of the pregnancy and provide a copy of the 
documentation to Allergan. 
  
11.0 STATISTICAL HYPOTHESIS AND METHODS OF ANALYSES 
11.1 
Power Calculation and Determination of Sample Size 
As this is a proof of concept study, no formal calculation of sample size was conducted. 
Approximately 70 participants will be enrolled to achieve approximately 60 completed 
participants.  
11.2 
Statistical Hypotheses and Level of Significance 
The null hypothesis is that there is no difference between the two devices, TrueTear and 
Thermalon, in the outcome of the exploratory measures.  The alternative hypothesis is there is a 
difference in the outcome. 
The hypothesis can be expressed as: 
H0: EN = ET  
HA: EN ≠ ET  
where EN represents the exploratory outcome result for the TrueTear neurostimulation group and 
ET represents the result for the Thermalon application group. 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 35 of 63 
01-JUN-2017   
11.3 
Randomization 
A computer-generated randomization will be used to assign study participants to their device 
application group. Study participants who meet the eligibility criteria and return for Visit 2 (Day 
0) will be randomized in a 1:1 ratio to either application of the TrueTear or the Thermalon 
device. 
11.4 
GENERAL STATISTICAL CONSIDERATIONS 
Statistical analyses will use a two-tailed test and will be evaluated at an α of 0.05 unless 
otherwise specified. The mean, standard deviation (SD), median, minimum and maximum will 
be presented for continuous variables such as participant age. For categorical variables, such as 
sex, the number for each category, the total number evaluated, and the percentage will be 
presented. 
11.5 
Participant Accountability and Missing Data 
Participants who withdraw from the study will be tabulated with the reasons for the withdrawal. 
Missing data will not be imputed. 
11.6 
Participant Demographic and Baseline Characteristics 
The demographic and baseline characteristics of the study population observed will be 
summarized by device group and for both groups combined.   
11.7 
Effectiveness Analyses 
This study does not include any effectiveness measures. 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 36 of 63 
01-JUN-2017   
12.0 FINAL CLINICAL STUDY REPORT 
A final clinical study report will be prepared after completion of the study. 
13.0 COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES 
13.1 
Protection of Human Participants 
 
Participant Informed Consent 
13.1.1
Informed consent should take place before any study-specific procedures are initiated. Signed 
and dated written informed consent should be obtained from each participant and/or from the 
participant’s parent or legal guardian prior to enrollment into the study. 
All ICFs should be approved for use by the Sponsor and receive approval/favorable opinion from 
an IRB prior to their use. If the consent form requires revision (e.g., due to a protocol 
amendment or significant new safety information), it is the Investigator’s responsibility to ensure 
that the amended informed consent is reviewed and approved by Sponsor and 
prior to 
submission to the governing IRB and that it is read, signed and dated by all participants 
subsequently enrolled in the study as well as those currently enrolled in the study. 
If informed consent is taken under special circumstances (oral informed consent), then the 
procedures to be followed should be determined by 
and/or study Sponsor and provided in 
writing by
 and/or study Sponsor prior to the consent process. 
 
Institutional Review Board (IRB) Approval 
13.1.2
This study is to be conducted in accordance with IRB regulations (U.S. 21 Code of Federal 
Regulations [CFR] Part 56.103). The Investigator should obtain appropriate IRB approval before 
initiating the study and re-approval at least annually. 
 
Ethical Conduct of the Study 
13.1.3
This study will be conducted in compliance with the protocol, Good Clinical Practices (GCPs), 
including the International Conference on Harmonisation (ICH) Guidelines, and the ethical 
principles that originated with the Declaration of Helsinki. 
 
Participant Confidentiality 
13.1.4
All personal study participant data collected and processed for the purposes of this study should 
be maintained by the Investigator and his/her staff with adequate precautions to ensure that the 
confidentiality of the data is in accordance with local, state, and federal laws and regulations. 
Monitors, auditors and other authorized representatives of Allergan, 
 IRB approving this 
study, the Food and Drug Administration (FDA), the Department of Health and Human Services 
(DHHS), and other domestic government agencies, will be granted direct access to the study 
participant’s original medical and study records for verification of the data and/or clinical trial 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 37 of 63 
01-JUN-2017   
procedures. Access to this information will be permitted to the aforementioned individuals to the 
extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health authorities 
in any country in which the study device may ultimately be marketed, but the participant’s 
identity will not be disclosed in these documents. 
13.2 
Documentation 
Source documents may include a participant’s medical records, hospital charts, clinic charts, the 
Investigator’s study participant files, as well as the results of diagnostic tests such as X-rays, 
laboratory tests, and electrocardiographs. The Investigator’s copy of the CRFs serves as the 
Investigator’s record of a participant’s study-related data. 
 
Retention of Documentation 
13.2.1
All study-related correspondence, participant records, consent forms, record of the 
distribution and use of all study device and copies of CRFs should be maintained on file for 
at least two years after the last approval of a marketing application in an ICH region and 
until there are no pending or contemplated marketing applications in an ICH region; or until 
at least two years have elapsed since the formal discontinuation of clinical development of 
the study device. These documents will be retained for a longer period if required by the 
applicable regulatory requirements or by an agreement with the Sponsor. It is the 
responsibility of the Sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
If the responsible Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping study records, custody should be transferred to a person who will 
accept the responsibility. The Sponsor should be notified in writing of the name and address 
of the new custodian. 
13.3 
REGULATORY STATUS 
A previous version of the TrueTear (formerly known as the Oculeve Intranasal Lacrimal 
Neurostimulator) received 
 It has been approved 
for marketing in Canada and Australia as well. The current version of TrueTear is an 
investigational device in the US. 
The Thermalon Dry Eye Compress is legally sold by its manufacturer 
 
 as a class I device in the USA and does not require 
premarket approval or notification. 
13.4 
Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Study Device 
All investigational devices will be clearly labeled “For Investigational Use Only.” The 
distribution and return of all devices will be recorded. Used disposable tips should be discarded 
after use; unused disposable tips should be returned to the Sponsor at the conclusion of the study. 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 38 of 63 
01-JUN-2017   
A device accountability log will be maintained by the site and will be filed in the Trial Master 
File. 
13.5 
Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Thermalon Dry Eye Compresses 
Thermalon Dry Eye Compresses will be purchased commercially and will be dispensed to 
participants in commercial packaging with a study label. Participants will be referred to the 
package insert or 
for product use and storage information. At the end of the 
study, participants will be asked to return their compress.  
13.6 
Recording of Data on Source Documents and Case Report Forms (CRFs) 
All participant data will be captured in the participant CRFs (i.e. source document). The 
Investigator is responsible for ensuring that study data is completely and accurately recorded on 
each participant’s CRF and all study-related materials. All study data should also be attributable, 
legible, contemporaneous, original and accurate. Recorded datum should only be corrected in a 
manner that does not obliterate, destroy, or render illegible the previous entry (e.g., by drawing a 
single line through the incorrect entry and writing the revision next to the corrected data). An 
individual who has corrected a data entry should make clear who made the correction and when 
by adding to the correction his/her initials as well as the date of the correction. 
13.7 
Amendments to the Protocol 
Any amendment containing major modifications (particularly if it may involve an increased risk 
to the participants) should be approved by the IRB before it may be implemented. No change in 
the conduct of the study can be instituted without written approval from the Sponsor. 
13.8 
Publications 
Information collected during this clinical study concerning TrueTear and results of the data 
obtained are proprietary and strictly confidential. The Sponsor reserves all rights to any such 
information. Authorship and manuscript composition will reflect cooperation among all parties 
involved in the study. Authorship will be established before writing the manuscript. Sponsor and 
will have the final decision regarding the manuscript and publication. 
14.0 REFERENCES 
 
1. 
Nelson JD, Shimazaki J, Benitez-del-Castillo JM, et al. The international workshop on 
meibomian gland dysfunction: report of the definition and classification subcommittee. 
Invest Ophthalmol Vis Sci. 2011;52(4):1930-1937. 
2. 
Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based 
perspective on prevalence and treatment. Ocul Surf. 2009;7(2 Suppl):S1-S14. 
3. 
Den S, Shimizu K, Ikeda T, Tsubota K, Shimmura S, Shimazaki J. Association between 
meibomian gland changes and aging, sex, or tear function. Cornea. 2006;25(6):651-655. 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 39 of 63 
01-JUN-2017   
4. 
DEWS. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee 
of the International Dry Eye WorkShop (2007). Ocul Surf. 2007;5(2):93-107. 
5. 
Hykin PG, Bron AJ. Age-related morphological changes in lid margin and meibomian 
gland anatomy. Cornea. 1992;11(4):334-342. 
6. 
Nien CJ, Massei S, Lin G, et al. Effects of age and dysfunction on human meibomian 
glands. Arch Ophthalmol. 2011;129(4):462-469. 
7. 
Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among 
US men: estimates from the Physicians' Health Studies. Arch Ophthalmol. 
2009;127(6):763-768. 
8. 
Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome 
among US women. Am J Ophthalmol. 2003;136(2):318-326. 
9. 
Sullivan BD, Evans JE, Dana MR, Sullivan DA. Influence of aging on the polar and 
neutral lipid profiles in human meibomian gland secretions. Arch Ophthalmol. 
2006;124(9):1286-1292. 
10. 
Lekhanont K, Rojanaporn D, Chuck RS, Vongthongsri A. Prevalence of dry eye in 
Bangkok, Thailand. Cornea. 2006;25(10):1162-1167. 
11. 
Lin PY, Tsai SY, Cheng CY, Liu JH, Chou P, Hsu WM. Prevalence of dry eye among an 
elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology. 
2003;110(6):1096-1101. 
12. 
Uchino M, Dogru M, Yagi Y, et al. The features of dry eye disease in a Japanese elderly 
population. Optom Vis Sci. 2006;83(11):797-802. 
13. 
Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland 
dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011;52(4):1922-1929. 
14. 
Gupta A, Heigle T, Pflugfelder SC. Nasolacrimal stimulation of aqueous tear production. 
Cornea. 1997;16(6):645-648. 
15. 
Friedman NJ, Butron K, Robledo N, Loudin J, Baba SN, A C. A nonrandomized, open-
label study to evaluate the effect of nasal stimulation on tear production in subjects with 
dry eye disease. Clinical Ophthalmology. 2016;10:795-798. 
16. 
Allergan. Studies OCUN-009 and OCUN-010. Data on File. 
17. 
LeDoux MS, Zhou Q, Murphy RB, Greene ML, Ryan P. Parasympathetic innervation of 
the meibomian glands in rats. Invest Ophthalmol Vis Sci. 2001;42(11):2434-2441. 
18. 
Foulks GN, Bron AJ. Meibomian gland dysfunction: a clinical scheme for description, 
diagnosis, classification, and grading. Ocul Surf. 2003;1(3):107-126. 
19. 
Linton RG, Curnow DH, Riley WJ. The Meibomian Glands: An Investigation into the 
Secretion and Some Aspects of the Physiology. Br J Ophthalmol. 1961;45(11):718-723. 
20. 
Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye 
syndrome. Prog Retin Eye Res. 2004;23(4):449-474. 
21. 
Dartt DA. Neural regulation of lacrimal gland secretory processes: relevance in dry eye 
diseases. Prog Retin Eye Res. 2009;28(3):155-177. 
22. 
Rocha EM, Alves M, Rios JD, Dartt DA. The aging lacrimal gland: changes in structure 
and function. Ocul Surf. 2008;6(4):162-174. 
23. 
Kossler AL, Wang J, Feuer W, Tse DT. Neurostimulation of the lacrimal nerve for 
enhanced tear production. Ophthal Plast Reconstr Surg. 2015;31(2):145-151. 
24. 
Allergan. Study OCUN-016. Data on File. 
25. 
Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and 
validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-621. 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 40 of 63 
01-JUN-2017   
 
15.0 APPENDICES 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 41 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 42 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 43 of 63 
01-JUN-2017   
15.2 
Appendix 2: Examination Procedures, Tests, Equipment, and Techniques 
 
Visual Acuity Procedures 
15.2.1
LogMAR visual acuity should be assessed using an ETDRS chart. The procedure used will be 
consistent with the recommendations provided for using the ETDRS eye chart. Visual acuity 
should be evaluated at the beginning of each visit in the study (i.e., prior to slit lamp 
examination). Participants should use the most recent correction to attain their corrected distance 
visual acuity (CDVA); if they forget their spectacles, this prescription can be placed in a trial 
frame. 
Equipment 
The visual acuity chart to be used is the ETDRS chart. If smaller reproduction (18" by 18", e.g., 
from Prevent Blindness) wall charts are used, the participant viewing distance should be exactly 
10 feet (or as specified by the manufacturer). In ALL cases, for purposes of standardizing the 
testing conditions during the study, all sites should use only ETDRS Series 2000 Chart 1 & 2, 
and the right eye should be tested first. For reflectance (wall) charts, the chart should be placed 
frontally and be well illuminated. 
Measurement Technique 
The chart should be at a comfortable viewing angle. The right eye should be tested first. The 
participant should attempt to read each letter, line-by-line, left to right, beginning with line 1 at 
the top of the chart. The participant should be told that the chart has letters only, no numbers. If 
the participant reads a number, s/he should be reminded that the chart contains no numbers, and 
the examiner should then request a letter in lieu of the number. The participant should be asked 
to read slowly to achieve the best identification of each letter. S/he is not to proceed to the next 
letter until s/he has given a definite response. 
If the participant changes a response (e.g., 'that was a "C" not an "O"') before s/he has read aloud 
the next letter, then the change should be accepted. If the participant changes a response having 
read the next letter, then the change is not accepted. The examiner should never point to the chart 
or to specific letters on the chart during the test. 
A maximum effort should be made to identify each letter on the chart. When the participant says 
s/he cannot read a letter, s/he should be encouraged to guess. If the participant identifies a letter 
as one of two letters, s/he should be asked to choose one letter and, if necessary, to guess. When 
it becomes evident that no further meaningful readings can be made, despite encouragement to 
read or guess, the examiner should stop the test for that eye. However, all letters on the last line 
should be attempted as letter difficulties vary and the last may be the only one read correctly. 
The number of letters missed or read incorrectly should be noted. 
LogMAR Visual Acuity Calculations 
The last line in which a letter is read correctly will be taken as the base logMAR reading. To this 
value will be added the number "N x 0.02" where 'N' represents the total number of letters 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 44 of 63 
01-JUN-2017   
missed up to and including the last line read. This total sum represents the logMAR visual acuity 
for that eye. 
Example: Participant correctly reads 4 of 5 letters on the 0.2 line, and 2 of 5 letters on the 0.1 
line. 
Base logMAR 
= 0.1 
N (total number of letters incorrect on line 0.2 as well as 0.1) 
= 4 
N x T (T=0.02) 
= 0.08 
Base logMAR + (N x T) 
= 0.1 + 0.08 
logMAR visual acuity 
= 0.18 
 
Repeat the procedure for the left eye. 
To provide standardized and well-controlled assessments of visual acuity during the study, all 
visual acuity assessments at a single site should be consistently done using the same lighting 
conditions and same correction if possible during the entire study. If the same correction cannot 
be used (i.e., a participant broke his/her glasses), the reason for the change in correction should 
be documented. 
Note: A clinically significant visual acuity decrease (defined as an increase of 0.22 or greater in 
logMAR score) from the Screening Visit (Visit 1) should be evaluated by the Investigator as a 
potential AE. 
 
Slit Lamp Biomicroscopy 
15.2.2
Slit lamp biomicroscopy will be performed during the study. Observations will be graded as 
Normal or Abnormal. Abnormal findings, which are clinically significant, will be described. The 
following will be examined at each visit: 
 
Cornea  
 
Conjunctiva  
 
Anterior Chamber 
 
Lid 
 
 
Tear Film Breakup Time Evaluated  
15.2.3
Slit-lamp settings should be adjusted to a magnification of 10x to 16x using a cobalt blue filter 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 45 of 63 
01-JUN-2017   
and yellow barrier filter placed directly in front of the objective lens of the slit lamp. 
Participants will be asked to tilt their heads slightly back and, starting with the right eye, 5 µL of 
2% preservative-free liquid sodium fluorescein will be applied to the lower cul-de-sac using a 
micropipette and sterile disposable tip. To thoroughly mix the fluorescein with the tear film, the 
participant will be instructed to blink several times over approximately 15 seconds. The 
participant will be instructed to blink three times naturally, then stare and not blink. Using a 
stopwatch, TBUT will be measured by the Investigator as the time from the last blink until 
one or more black (dry) spots appear in the precorneal tear film. The time is to be recorded to 
two significant digits. After the first measurement, the participant will be instructed to blink 
naturally three additional times and a second measurement will be taken. The procedure will be 
repeated for a third measurement. After a 60-second rest period, the entire procedure will be 
repeated for the left eye. 
 
Corneal and Conjunctival Sodium Fluorescein Staining 
15.2.4
Immediately following completion of TBUT evaluation for both eyes, the entire cornea will be 
evaluated for staining, starting with the right eye. The examination will be performed with the 
slit lamp at approximately 10x magnification using a cobalt blue filter and yellow barrier filter 
placed directly in front of the objective lens of the slit lamp. Grading of the resulting corneal 
staining will be based on the National Eye Institute (NEI) grading system (score between 0 and 
3), where 0 corresponds to no staining, 1 corresponds to mild staining, 2 corresponds to moderate 
staining, and 3 corresponds to severe staining.  
The schematic representations of the five corneal and six conjunctival regions per eye are shown 
below. The upper eyelid is lifted slightly to grade the entire corneal surface. For corneal staining, 
the maximum possible score per eye is 15. This procedure should then be repeated in the other 
eye. Once grading of the cornea is complete, grading of the conjunctiva can occur.  
To grade conjunctival staining, the six nasal and temporal conjunctival regions will be graded. 
To grade the temporal zone, the participant should be instructed to look nasally; to grade the 
nasal zone, the participant should be instructed to look temporally. A standardized grading 
system of 0 to 3 is used for each for the six areas depicted per eye as shown in the diagram 
below. For conjunctival staining, the maximum possible score per eye is 18. This procedure 
should then be repeated in the other eye. 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 46 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 47 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 48 of 63 
01-JUN-2017   
 
 
Figure 3  Target Area of Cotton Swab Nasal Stimulation 
 
 
Symptom Questionnaires 
15.2.6
 
 
 
 
 
 
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 49 of 63 
01-JUN-2017   
 
 
 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 50 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 51 of 63 
01-JUN-2017   
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 52 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 53 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 54 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 55 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 56 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 57 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 58 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 59 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 60 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 61 of 63 
01-JUN-2017   

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 62 of 63 
01-JUN-2017   
15.3 
Appendix 3: Sponsor and 
Approvals 
Protocol Title: 
Prospective, Open-Label, Randomized, Proof of Concept Study Exploring 
Application of TrueTear™ for the Treatment of Meibomian Gland Disease 
Protocol Number: 
OCUN-023 
 

Clinical Trial Protocol: OCUN-023 
 
Sponsor: Allergan, Inc. 
Version 1.1 
Confidential  
Page 63 of 63 
01-JUN-2017   
15.4 
Appendix 4: Investigator’s Signature 
 
Protocol Title: 
Prospective, Open-Label, Randomized, Proof of Concept Study 
Exploring Application of TrueTear™ for the Treatment of Meibomian 
Gland Disease 
 
Protocol Number: 
OCUN-023 
 
 
I agree to implement and conduct the study diligently and in strict compliance with the protocol, 
good clinical practices and all applicable laws and regulations. I agree to maintain all 
information supplied by
 and the sponsor in confidence and, when this information is 
submitted to an Institutional Review Board (IRB) or another group, it will be submitted with a 
designation that the material is confidential. 
I have read this protocol in its entirety, including the above statement, and I agree to all aspects. 
Signed:   
        Date: 
 
 
 
Name:  
 
 
 
Title:  
 
 
 
Site:  
 
 
 
Address:  
 
 
 
Phone Number: