A 40-week Open-Label Extension Study to Evaluate TNX-102 SL 5.6 mg Taken Daily at Bedtime in Patients With PTSD
Phase: PHASE3
Conditions: PTSD
Sponsor: Tonix Pharmaceuticals, Inc.



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INVESTIGATOR’S AGREEMENT 
I have read the TNX-CY-P306 protocol and agree to conduct the study as outlined.  I agree to 
maintain the confidentiality of all information received or developed in connection with this 
protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 

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PROCEDURES IN CASE OF EMERGENCY 
Table 1: Emergency Contact Information 
 
 
 
 
 
 
 
 
 
 
 
 

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2. 
SYNOPSIS 
Name of Sponsor/Company: 
Tonix Pharmaceuticals, Inc. 
Name of Investigational Product: 
Tonmya®/TNX-102 SL (Cyclobenzaprine HCl Sublingual Tablets) 
Name of Active Ingredient: 
Cyclobenzaprine HCl 
Title of Study: 
A 40 to 52-Week Open-Label Extension Study to Evaluate TNX-102 SL Taken Daily at Bedtime 
in Patients with PTSD 
Study period (months): 18 
Estimated date first patient enrolled:  April 2018 
Estimated date last patient completed: September 2019 
Phase of development: 3 
 
Objectives 
Primary: 
The primary objective of the study is to evaluate the long-term safety of TNX-102 SL 5.6 mg taken 
daily at bedtime over an additional 40 to 52 weeks in patients with PTSD who have participated in a 
double-blind lead-in P301 or HONOR study.  Some patients will have also participated in an initial 
12-week open-label extension study (TNX-CY-P303).  This will provide at least 52 weeks of TNX-
102 SL 5.6 mg exposure data for at least 50 patients.   
Methodology:  
This is an open-label, extension trial designed to evaluate safety of additional 40 to 52 weeks of TNX-
102 SL 5.6 mg taken daily at bedtime for the treatment of PTSD. There are two possible “tracks” 
patients can use to enroll into this study: 
Track A:  patients that complete the double-blind lead-in HONOR study and complete or are 
active (at the time of study discontinuation) in the 12-week open-label extension study, P303, 
and received active drug in the 12-week double-blind lead-in study, P301/HONOR. 
Track B:  patients that are currently enrolled in the double-blind lead-in P301/HONOR study that 
has been discontinued due to results of an interim analysis or are active (at the time of study 
discontinuation) in the 12-week open-label extension study, P303, and received placebo in the 
12-week double-blind lead-in study, P301/HONOR. 
The study will consist of 5 or 6 in-clinic study visits, including Baseline Visit 1 (Day 0, which is 
anticipated to be the same visit as the last visit of the 12-week open-label extension study P303 for 
Track A patients), followed by in-clinic visits after 7, 16, 28 and 40 weeks of open-label treatment.  
Patients who are active in the 12-week double-blind lead-in study (P301/HONOR) at the time of 
enrollment to P306 will also have a 2-week phone check-in visit. All Track B patients will have 52 
weeks of open-label treatment and a Visit 7.  For patients enrolled from the discontinued double-blind 
lead-in study, P301/HONOR, the P306 Baseline Visit will occur in lieu of an early termination visit.   
Patient safety parameters recorded at the final visit in the double-blind lead-in HONOR study (which 
is the baseline visit in the 12-week open-label extension study P303) can also be used as the baseline 
safety values for the P306 extension study for Track A patients.  Patients will attend clinic visits at 7-, 
9-, and 12-week intervals as indicated in the study visit schedule.  Eligible patients who provide 
written informed consent will be provided with a supply of TNX-102 SL 2.8 mg tablets sufficient for 

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dosing until their next scheduled in-clinic study visit. At each clinic visit, patients will return their 
TNX-102 SL medication and will receive sufficient supplies to last them until the next scheduled 
visit.  Patients will also have the option to have blood drawn for pharmacogenomic testing.   
Number of patients (planned):  
The study will enroll up to 200 patients. 
Inclusion/Exclusion Criteria: 
Inclusion criteria: 
1. The patient has either a) completed a double-blind lead-in HONOR study and completed or is 
active (at the time of study discontinuation) in the 12-week open-label extension study, P303, 
or b) is currently enrolled in the double-blind lead-in HONOR study that has been 
discontinued due to results of an interim analysis, and is judged by the investigator as 
reasonably compliant, with at least 60% compliance with study medication usage (based on 
drug accountability). 
2. The patient has provided written informed consent to participate in this extension study.  
Note: Separate written, signed informed consent will be required if the patient is to participate 
in the optional pharmacogenomic assessment.  A decision not to participate in the optional 
pharmacogenomic testing will not affect the patient’s eligibility for the main study. 
3. The patient met all prior inclusion and exclusion requirements for the double-blind lead-in 
HONOR study, or the site received medical monitor approval for the patient to remain in the 
lead-in study after the retrospective discovery of an entry violation that did not pose any 
threat to the patient’s safety or well-being.  
4. During the course of the lead-in HONOR study or 12-week open-label extension P303 study, 
the patient has had no intervening medical conditions including pregnancy, clinically 
significant increase in suicidal ideation (plan or intent) or significant worsening of 
depression, newly arising clinically significant abnormal laboratory tests, or any clinically 
significant, uncontrolled, or unstable medical or surgical condition that could affect the 
patient’s ability to participate in the study or potentially compromise the patient’s well-being 
during the study. 
5. The patient does not require treatment with a potent (strong) cytochrome P450 subtype 3A4 
(CYP3A4) inhibitor, or St. John’s wort. 
6. The patient is willing to refrain from use of all other formulations of cyclobenzaprine for the 
duration of the study. 
7. The patient is willing to refrain from use of monoamine oxidase inhibitors for the duration of 
the study. 
8. Female patients of childbearing potential continue to agree to practice one of the medically 
acceptable methods of birth control detailed in the lead-in study. 
 
Exclusion Criteria:  
There are no exclusion criteria for this study. 
 
Investigational product, dosage and mode of administration: 

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Name: Tonmya®1/TNX-102 SL (cyclobenzaprine HCl sublingual tablets) 
Dose, route, frequency: 2 tablets of TNX-102 SL 2.8 mg taken simultaneously and sublingually 
(under the tongue) each day at bedtime starting on Day 0 for 40 to 52 weeks. 
Duration of treatment: 
40 to 52 weeks 
Reference therapy, dosage and mode of administration: None 
Criteria for evaluation: 
The primary objective of the study is to evaluate the safety of bedtime treatment with TNX-102 SL 
5.6 mg for an additional 40 to 52 weeks in patients with PTSD who have either completed the double-
blind lead-in HONOR study and completed or are active (at the time of study discontinuation) in the 
12-week open-label extension study, P303, or were enrolled in the double-blind lead-in HONOR 
study that has been discontinued due to results of an interim analysis.  Safety will be assessed by the 
monitoring and recording of AEs, clinical laboratory tests, vital signs, the monitoring of suicidality 
using the Columbia Suicide Rating Scale (C-SSRS) scale, and the monitoring of depressive 
symptoms using the Beck Depression Inventory (BDI-II). Safety as well as durability of response will 
also be assessed by the monitoring of PTSD symptoms using the PTSD Checklist-Specific Version 
(PCL-S) at Visit 5 (Week 28) and Visit 6 (Week 40) in order to monitor for any potential worsening 
of PTSD symptoms or its symptoms clusters during the final 12-weeks of the study. Patients enrolled 
under Track B will also have an additional PCL-S evaluated for safety at their Visit 7 (Week 52). 
Limited efficacy assessments consisting of the CGI-I, SDS, PROMIS Sleep Disturbance and the BDI-
II will be collected at each visit. The PCL-S will be used for efficacy assessments at Visits 5 and 6 
only. 
Statistics 
Analysis Population:  
The Safety Population will comprise all patients who have been exposed to TNX-102 SL. 
 
Safety Analyses:   
Safety data will be summarized as a single treatment group receiving 1 or more doses of TNX-102 SL 
5.6 mg.  Adverse events will be coded using the same version of the Medical Dictionary for 
Regulatory Activities (MedDRA) as used for the lead-in HONOR study and will be summarized 
overall and by preferred term and system organ class (SOC).  Adverse events will also be summarized 
by severity and relationship to study drug.  Serious AEs and AEs leading to discontinuation of study 
drug will also be summarized. Adverse events that are ongoing in the 12-week open-label extension 
study P303 or the lead-in double blind HONOR study will be transcribed into the eCRF.  All other 
adverse events that are reported after starting TNX-102 SL in this extension study, or that worsen 
after entry into this extension study, will be considered newly emergent AEs (NEAEs), even if the 
type of event was previously reported (and resolved) during either the HONOR study or the 12-week 
open-label extension study. 
Actual values and change from baseline for clinical laboratory test results, vital sign measurements, 
depression status via the BDI-II and PTSD symptom status via the PCL-S, will be summarized at 
endpoint using descriptive statistics (n, mean, SD, median, minimum, and maximum).  The number of 
                                                 
1 Tonmya is the FDA conditionally accepted proposed proprietary name for TNX-102 SL for the treatment of 
PTSD. 

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patients with baseline and treatment-emergent suicidal ideation and/or suicidal behavior or self-
injurious behavior, based on the C-SSRS, will be summarized by treatment group. 
 
Efficacy Analyses: 
Descriptive statistics by study visit will be displayed for: 
▪ 
Proportion of patients with a CGI-I score of “very much improved” or “much improved” 
from baseline 
▪ 
Change from baseline in the SDS 
▪ 
Change from baseline in patients’ quality of sleep score using the PROMIS Sleep 
Disturbance scale  
▪ 
Change from baseline in BDI-II total score 
▪ 
Change from Visit 5 to Visit 6 in PCL-S total score 
 
Pharmacogenomic Analyses: 
Potential genetic determinants of treatment response will be examined by the assessment of genetic 
variants in relation to treatment outcome. A blood sample will be obtained from patients who have 
signed a separate informed consent form for the pharmacogenomic analyses.  The blood sample can 
be obtained as soon as the patient has agreed to be tested and has signed the separate informed 
consent form; i.e., the blood draw is not tied to any specific study visit, hence it can be obtained at 
any time.   
 
The first step of the pharmacogenomic analyses will involve exome sequencing and analysis for 
allelic polymorphisms related to treatment response to TNX-102 SL. It is presumed that unused 
sample will be stored up to fifteen years, and potentially utilized to develop a pharmacogenomic test 
for determining likelihood of treatment response to TNX-102 SL.   

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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................4 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................8 
4. 
INTRODUCTION ......................................................................................................14 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................15 
5.1. 
Primary Objective .......................................................................................................15 
5.2. 
Secondary Objectives .................................................................................................15 
6. 
INVESTIGATIONAL PLAN .....................................................................................16 
6.1. 
Overall Study Design ..................................................................................................16 
6.2. 
Number of Patients and Treatment Assignment .........................................................16 
6.3. 
Study Endpoints ..........................................................................................................17 
6.3.1. 
Safety ..........................................................................................................................17 
6.3.2. 
Efficacy .......................................................................................................................17 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................17 
7.1. 
Informed Consent .......................................................................................................17 
7.2. 
Inclusion Criteria ........................................................................................................18 
7.3. 
Patient Exclusion Criteria ...........................................................................................18 
7.4. 
Withdrawal Criteria ....................................................................................................19 
8. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................20 
8.1. 
Study Drug Packaging, and Labeling and Storage .....................................................20 
8.2. 
Dosing Instructions .....................................................................................................20 
8.3. 
Dispensing Instructions ..............................................................................................21 
8.4. 
Release of Clinical Study Supplies to the Investigator ...............................................21 
8.5. 
Concomitant Medications ...........................................................................................21 
8.6. 
Study Drug Accountability and Reconciliation ..........................................................22 
9. 
STUDY VISITS AND PROCEDURES .....................................................................23 
9.1. 
Visit 1 – Screening/Baseline (Week 0, Day 1) ...........................................................23 
9.1.1. 
Informed Consent .......................................................................................................23 
9.1.2. 
Screening Overview ....................................................................................................23 

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9.1.3. 
Patient Numbering ......................................................................................................23 
9.1.4. 
Pharmacogenomic Assessment ...................................................................................24 
9.1.5. 
Visit 1 Baseline Assessments/Procedures (Week 0) ..................................................24 
9.2. 
Visit 2 (Telephone Visit: Week 2) ..............................................................................25 
9.3. 
Visits 3, 4, and 5 (Weeks 7, 16, and 28) .....................................................................25 
9.4. 
Visit 6 (Week 40) ........................................................................................................26 
9.5. 
Early Termination (ET) ..............................................................................................27 
9.6. 
Unscheduled Visits .....................................................................................................28 
10. 
STUDY ASSESSMENTS ..........................................................................................29 
10.1. 
Screening Assessments ...............................................................................................29 
10.2. 
Efficacy Assessments .................................................................................................29 
10.2.1. 
Clinical Global Impression of Improvement (CGI-I) .................................................29 
10.2.2. 
Sheehan Disability Scale (SDS) .................................................................................29 
10.2.3. 
PROMIS Sleep Disturbance Scale ..............................................................................29 
10.2.4. 
Beck Depression Index (BDI-II) ................................................................................30 
10.2.5. 
PTSD Checklist-Specific Version (PCL-S) ................................................................30 
10.3. 
Pharmacogenomics Testing ........................................................................................30 
10.4. 
Safety Parameters .......................................................................................................30 
10.4.1. 
Adverse Events (AEs) .................................................................................................31 
10.4.1.1. 
Columbia-Suicide Severity Rating Scale (C-SSRS) ...................................................31 
10.4.1.2. 
Safety Planning Intervention (SPI) .............................................................................31 
10.4.1.3. 
Visual Examination of Oral Cavity ............................................................................32 
10.4.1.4. 
Vital Signs ..................................................................................................................32 
10.4.1.5. 
Clinical Laboratory Assessments ...............................................................................32 
11. 
DEFINITIONS, RECORDING, AND REPORTING OF ADVERSE 
EVENTS AND PREGNANCY ..................................................................................33 
11.1. 
Definition of Adverse Events .....................................................................................33 
11.2. 
Adverse Event Recording ...........................................................................................34 
11.2.1. 
Coding the Adverse Event ..........................................................................................34 
11.2.2. 
Severity of Adverse Event ..........................................................................................34 
11.2.3. 
Relationship of Adverse Events to Study Drug ..........................................................34 
11.3. 
Serious Adverse Events (SAEs) and Serious Adverse Drug Reactions .....................35 
11.4. 
Pregnancy ...................................................................................................................37 

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12. 
STATISTICS ..............................................................................................................38 
12.1. 
Evaluation of Safety ...................................................................................................38 
12.2. 
Evaluation of Efficacy ................................................................................................38 
12.3. 
Estimate of Sample Size .............................................................................................38 
12.4. 
Assessment of Demographic and Baseline Characteristics and Patient 
Disposition ..................................................................................................................39 
13. 
PROCEDURES FOR MODIFYING THE PROTOCOL OR 
TERMINATING THE STUDY .................................................................................40 
13.1. 
Protocol Modifications and Deviations ......................................................................40 
13.2. 
Study Termination ......................................................................................................40 
14. 
ETHICAL CONSIDERATIONS................................................................................41 
14.1. 
Ethical Conduct of the Study ......................................................................................41 
14.2. 
Ethics Committee/Institutional Review Board (EC/IRB) Review .............................41 
14.3. 
Written Informed Consent ..........................................................................................41 
15. 
DATA HANDLING AND RECORDKEEPING .......................................................43 
15.1. 
Maintaining Privacy and Confidentiality....................................................................43 
15.2. 
Maintaining Essential Clinical Documents ................................................................43 
15.3. 
Data Handling .............................................................................................................44 
15.4. 
Case Report Forms (CRFs) .........................................................................................44 
15.5. 
Screening Records ......................................................................................................44 
15.6. 
Clinical Laboratory Certification ................................................................................44 
15.7. 
Site Monitoring and Tonix’s Right to Review Records .............................................45 
15.8. 
Audits and Inspections ................................................................................................45 
16. 
CONFIDENTIALITY ................................................................................................46 
16.1. 
Protection of Patient Anonymity ................................................................................46 
16.2. 
Confidentiality of Study Information .........................................................................46 
16.3. 
Publication of Data and Protection of Trade Secrets ..................................................46 
17. 
LIST OF REFERENCES ............................................................................................48 
18. 
APPENDICES ............................................................................................................49 
APPENDIX 1. STUDY DESIGN AND SCHEDULE OF ASSESSMENTS .............................49 
APPENDIX 2. LIST OF CYP3A INHIBITORS ........................................................................51 
APPENDIX 3. AMRIX® PACKAGE INSERT (DATED MAY 2018) .....................................52 
 

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LIST OF TABLES 
Table 1: 
Emergency Contact Information ...................................................................................3 
Table 2: 
Clinical Laboratory Assessments ...............................................................................32 
Table 3: 
Medical Monitoring Contact Information ..................................................................36 

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 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviation or 
Specialist Term 
Explanation 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BDI-II 
Beck Depression Inventory–II 
BMI 
Body Mass Index 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CGI-I 
Clinical Global Impression- Improvement from Initiation of Treatment 
CK 
Creatinine Kinase 
CoC 
Certificate of Confidentiality 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CYP3A4 
Cytochrome P450 subtype 3A4 
e.g. 
Exempli gratia (for example) 
EC 
Ethics Committee 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HCl 
Hydrochloride 
HIPAA 
Health Insurance Portability and Accountability Act 
i.e. 
id est (that is) 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
MCH 
Mean corpuscular hemoglobin 

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Abbreviation or 
Specialist Term 
Explanation 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
Milligram(s) 
N, n 
Number (of patients) 
NA 
Not applicable 
NEAE 
Newly Emergent Adverse Event 
PCL-S 
PTSD Checklist-Specific Version 
PROMIS 
Patient-Reported Outcome Measurement Information System 
PTSD 
Posttraumatic Stress Disorder 
RBC 
Red blood cell 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SDS 
Sheehan Disability Scale 
SL 
Sublingual 
SNRIs 
Serotonin–norepinephrine reuptake inhibitors 
SOC 
System Organ Class 
SOP 
Standard Operating Procedures 
SPI 
Safety Planning Intervention 
SSRIs 
Selective serotonin reuptake inhibitors 
TNX-102 SL 
Cyclobenzaprine HCl sublingual tablets 
Tonmya 
FDA conditionally accepted proposed proprietary name for TNX-102 SL for the 
treatment of PTSD 
US 
United States 
VA 
Veteran’s Administration 
WBC 
White blood cell 
WHO 
World Health Organization 

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4. 
INTRODUCTION 
The background information provided in the lead-in study protocol and the most current TNX-
102 SL Investigator’s Brochure is relevant to this extension study.  
 
 
 
 
 
 
 

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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
The primary objective of the study is to evaluate the long-term safety of TNX-102 SL taken daily 
at bedtime over an additional 40 to 52 weeks in patients with PTSD who have participated in a 
double-blind lead-in HONOR study and possibly a 12-week open-label extension study P303. 
5.2. 
Secondary Objectives 
The secondary objective of the study is to evaluate the long-term effect of TNX-102 SL taken 
daily at bedtime over an additional 40 to 52 weeks in patients with PTSD who have participated 
in a double-blind lead-in HONOR study and possibly a 12-week open-label extension study 
P303. 

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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a 40 to 52-week, multicenter, open-label extension study designed to establish long-term 
safety exposure and to examine the long-term effect with daily bedtime dosing of TNX-102 SL 
5.6 mg (2 x 2.8mg tablets) in patients with PTSD.  This study will be conducted at approximately 
35 sites in the United States (US).  
Patients who have either: (a) completed the double-blind lead-in study and complete, or are 
active (at the time of study discontinuation) in the 12-week open-label extension study, P303; or 
(b) are currently enrolled in the double-blind lead-in study (HONOR study) that has been 
discontinued due to results of an interim analysis , will be eligible.  For Track A patients, this 
extension study consists of 5 in-clinic visits, including the Screening/Baseline visit and visits 
after 7, 16, 28 and 40 weeks of treatment (Visits 3-6).  There will also be a telephone visit after 
two weeks of treatment (Visit 2) for patients enrolling from the double-blind lead-in study, 
P301/HONOR.  The total treatment duration of this study will be 40 weeks for patients enrolled 
under Track A criteria, and 52 weeks for patients enrolled under Track B criteria.  Therefore, the 
maximum total duration of continuous treatment with TNX-102 SL could be approximately 64 
weeks for those patients assigned to TNX-102 SL in the lead-in HONOR study who then also 
completed the 12-week open-label extension study P303.  
For patients enrolling from the open-label extension study, P303, there is no need to repeat 
assessments at Visit 1 for this study, if the patient enrolls and initiates study treatment within 
fourteen days of completing the 12-week open-label extension study P303.  For patients who are 
active in the double-blind lead-in study, P301/HONOR, all Baseline procedures and assessments 
will be completed at Visit 1. 
After the patient has participated in the lead-in HONOR study or the open-label extension study, 
P303, and has consented to participate in this open-label extension study, patients will be 
dispensed a 7-week supply of open-label TNX-102 SL tablets (3 bottles) and will be instructed to 
take 2 tablets of study drug sublingually daily at bedtime, starting on the evening of Visit 1.  A 
phone visit will be completed after 2 weeks of treatment for patients enrolling from the double-
blind lead-in study, P301/HONOR.  All patients will return to the study center for safety and 
efficacy assessments at Weeks 7, 16, 28, and 40 (or early termination). Patients enrolled under 
Track B criteria will continue to dose for an additional 12 weeks and have the last study visit at 
Week 52.  Patients will return their TNX-102 SL medication (including empty bottles) at these 
visits.  Patients will also receive a 9-week supply of TNX-102 SL (4 bottles) at the Week 7 visit, 
and a 12-week supply (5 bottles) at the Week 16, 28 and 40 (Week 40 for Track B patients only) 
visits.  Patients will be allowed to take other medications deemed appropriate by their health care 
providers to manage their PTSD and other conditions, including currently approved PTSD 
therapies.  See Section 8.5 for a discussion of allowed concomitant treatments.  
The study timeline and events schedule is provided in Appendix 1. 
6.2. 
Number of Patients and Treatment Assignment 
Up to 200 patients will enroll into this study.  Eligible patients will either have completed a 
double-blind lead-in HONOR study and participated in a 12-week open-label study P303 or will 

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have been currently enrolled in a double-blind lead-in HONOR study when that study was 
discontinued due to results of an interim analysis. 
All patients will be assigned to TNX-102 SL, 5.6 mg regardless of which treatment arm they 
were randomized to in the lead-in HONOR study.   
6.3. 
Study Endpoints 
6.3.1. 
 Safety 
Safety will be assessed by: 
▪ Adverse events (AEs) and serious AEs (SAEs) throughout the entire duration of the 
study, including assessment of AEs involving the oral cavity 
▪ Change from baseline in clinical laboratory test results 
▪ Changes from baseline indicative of increased suicidal ideation or behavior as assessed 
by the Columbia Suicide Severity Rating Scale (C-SSRS) 
▪ Change from baseline in Beck Depression Inventory-II (BDI-II) 
▪ Changes from baseline in vital signs and weight 
▪ Track A patients only: Change from Visit 5 to Visit 6 in PTSD Checklist-Specific 
Version (PCL-S) 
▪ Track B patients only: Change from Visit 5 to Visit 7 in PTSD Checklist-Specific 
Version (PCL-S) 
6.3.2. 
Efficacy  
Descriptive statistics by treatment and study visit will be displayed for a number of efficacy 
endpoints including: 
▪ Proportion of patients with a Clinical Global Impression-Improvement from Initiation of 
Treatment (CGI-I) score of “very much improved” or “much improved” from baseline 
▪ Change from baseline in the Sheehan Disability Scale (SDS)  
▪ Change from baseline in patients’ quality of sleep using the Patient-Reported Outcome 
Measurement Information System (PROMIS) Sleep Disturbance scale  
▪ Change from baseline in BDI-II score 
▪ Change from Visit 5 to Visit 6 in PTSD Checklist-Specific Version (PCL-S) 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1. 
Informed Consent 
A potential patient may be screened for eligibility only after the nature of the study, its purpose, 
and any other information relevant to the patient’s decision to participate have been explained to 
him or her and the patient has voluntarily confirmed his or her willingness to participate.  The 
investigator will determine the potential patient’s suitability for the study by interviewing the 

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patient and by reviewing the patient’s experience in the double-blind lead-in HONOR study 
and/or 12-week open-label extension study P303.  
Informed consent is documented by means of a written, signed, and dated informed consent form 
(ICF).  Separate written, signed informed consent must be obtained if the patient is to participate 
in the optional pharmacogenomic assessment.  Additional information is provided in 
Section 14.3. 
7.2. 
Inclusion Criteria 
1. The patient has either a) completed the double-blind lead-in study and completed or is 
active (at the time of study discontinuation) in the 12-week open-label extension study 
(P303), or b) is currently enrolled in the double-blind lead-in study that was discontinued 
due to results of an interim analysis, and is judged by the investigator as reasonably 
compliant, with at least 60% compliance with study medication usage (based on drug 
accountability). 
2. The patient has provided written informed consent to participate in this extension study.  
Note: Separate written, signed informed consent will be required if the patient is to 
participate in the optional pharmacogenomic assessment.  A decision not to participate in 
the optional pharmacogenomic testing will not affect the patient’s eligibility for the main 
study. 
3. The patient met all prior inclusion and exclusion requirements for the double-blind lead-
in study, or the site received medical monitor approval for the patient to remain in the 
lead-in study after the retrospective discovery of an entry violation that did not pose any 
threat to the patient’s safety or well-being.  
4. During the course of the lead-in study or 12-week open-label extension study, the patient 
has had no intervening medical conditions including pregnancy, clinically significant 
increase in suicidal ideation (plan or intent) or significant worsening of depression, newly 
arising clinically significant abnormal laboratory tests, or any clinically significant, 
uncontrolled, or unstable medical or surgical condition that could affect the patient’s 
ability to participate in the study or potentially compromise the patient’s well-being 
during the study. 
5. The patient does not require treatment with a potent (strong) cytochrome P450 subtype 
3A4 (CYP3A4) inhibitor, or St. John’s wort. 
6. The patient is willing to refrain from use of all other formulations of cyclobenzaprine for 
the duration of the study. 
7. The patient is willing to refrain from use of monoamine oxidase inhibitors for the 
duration of the study. 
8. Female patients of childbearing potential continue to agree to practice one of the 
medically acceptable methods of birth control detailed in the lead-in study. 
7.3. 
Patient Exclusion Criteria  
There are no exclusion criteria for this study. 

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7.4. 
Withdrawal Criteria 
There are no pre-specified withdrawal criteria for this study.  In accordance with the Declaration 
of Helsinki, human patients have the right to withdraw from the study at any time for any reason.  
The investigator and Tonix also have the right to remove patients from the study.  Additional 
information regarding withdrawal or discontinuation of patients is described in detail in 
Section 9.6. 

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8. 
STUDY DRUG MATERIALS AND MANAGEMENT 
8.1. 
Study Drug Packaging, and Labeling and Storage 
The study medication bottles will be labeled minimally with the following information:  study 
number TNX-CY-P306 (P306), sponsor name and address, bottle number, drug name, quantity, 
storage conditions, usage instructions, and caution statements for investigational new drug, i.e., 
Caution: New Drug Limited by United States Law to Investigational Use, and Keep Out of 
Reach of Children and Pets. 
Each study medication bottle will contain 40 tablets.  Since the patient will dose with two tablets 
sublingually each night, three bottles will be dispensed to each patient at Visit 1/Baseline.  Four 
bottles will be dispensed at Week 7 and five bottles at Weeks 16, 28 and 40 (Week 40 for Track 
B patients only); this will provide the patient with enough study drug between visits, plus 
additional tablets to cover loss and/or visit window variability.  The patient should be instructed 
to take all the tablets in one bottle before opening another bottle.  The patient should be 
instructed to keep this study medication in a safe location out of extreme environmental 
conditions and out of the reach of children and pets, and that this medication is not to be taken by 
any individual other than the study patient.  Each patient will also be instructed that they will be 
expected to return all bottles and all unused study medication at each clinic visit; unused 
medication will be counted to assess compliance with study drug treatment. 
Storage of the study drug at the investigational site should be under locked and secure conditions 
with limited staff access.  Study drug should be stored at 20-25°C/68-77°F in a temperature/ 
humidity-monitored room; however, brief excursion (15-30°C/59-86°F) as defined in the Study’s 
Reference Manual (IP Receipt and Storage) is permitted without sponsor’s approval. 
8.2. 
Dosing Instructions 
Patients will be instructed to take two (2) TNX-102 SL 2.8 mg tablets sublingually, placed 
simultaneously under the tongue, each evening at bedtime starting on evening of Day 0 and 
continuing without interruption for 40 to 52 weeks.  The study drug should be taken at bedtime 
after teeth brushing and other oral care has been completed.  The mouth/sublingual area should 
be moist at the time of dosing, so the patient should drink a few sips of water prior to dosing, 
especially if prone to dry mouth.  Patients will be instructed to place the two TNX-102 SL 2.8 
mg tablets under their tongue and keep them there until they have dissolved.  They should not 
swallow, crush or chew the tablets.  Patients should not eat or drink (or chew gum) for at least 15 
minutes after dosing, and preferably not until morning.  Patients will be reminded that only two 
(2) tablets are allowed per day. Note: In the event that the patient misses a dose, instruct the 
patient to continue dosing with two (2) tablets the next evening; i.e., they should not take more to 
make up for the missed dose. 
Patients should also be reminded to keep the desiccant in the bottle after opening and to screw 
the cap on tightly after dosing. 
 

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8.3. 
Dispensing Instructions 
Each enrolled patient will be assigned 3, 4 or 5 bottles of TNX-102 SL at each dispensing visit.  
Bottles of TNX-102 SL tablets are numbered and will be supplied to sites as open stock.  Patients 
are reminded to open and use one bottle of TNX-102 SL tablets at a time. 
8.4. 
Release of Clinical Study Supplies to the Investigator 
Tonix or Tonix’s designee’s standard operating procedures (SOP) for releasing clinical trial 
supplies to the site will be followed. 
8.5. 
Concomitant Medications  
Many of the restrictions in the lead-in study related to concomitant medications and trauma-
focused psychotherapy will be relaxed.  Therefore, patients may utilize antidepressants, mood 
stabilizers, anticonvulsants, benzodiazepines, stimulants, and opioids, if needed, unless 
specifically excluded as outlined below.  Patients may take medications to help them sleep, per 
the judgment of the investigator.  
Any concomitant medications or other treatments, including dietary supplements, must be 
recorded in the patient’s medical record and case report form along with the indication, dose and 
dates of treatment.  
The following medications are specifically excluded during the study and patients must agree to 
refrain from use of these medications during the study:   
• Any other forms of cyclobenzaprine (FLEXERIL®, AMRIX®, FEXMID®, or generic 
equivalents) continue to be specifically excluded during the study and patients must 
agree to refrain from use of these medications during the study.  
• Monoamine oxidase inhibitors (tranylcypromine, phenelzine, isocarboxazid, and 
selegiline)   
• Cytochrome P450 3A4 inhibitors (strong ones only) (refer to Appendix 2 for a list).  
• St. John’s wort  
NOTE: Patients initiating treatment with antidepressants, tramadol or other opioids, triptans, or 
any other serotonergic medication should be cautioned about the possibility of serotonin 
syndrome which has been reported in patients receiving cyclobenzaprine with selective serotonin 
reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and other 
serotoninergic agents. (See Appendix 3, AMRIX® Package Insert, Warnings Section).  The 
patient should be instructed to call the clinic immediately in the event of any of the warning 
signs or symptoms of serotonin syndrome, as outlined in the informed consent.  The investigator 
should carefully review the patient’s complete list of medications when considering new 
treatments and the site should ask the patient to call the site (or return for an unscheduled clinic 
visit) within one week after adding a new serotonergic therapy (or increasing the dose of a prior 
treatment).  

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8.6. 
Study Drug Accountability and Reconciliation 
All patients will be expected to bring their bottles of study medication with them to study visits.  
The site staff will inspect the medication bottles and perform a count of the tablets remaining in 
the bottles and the number of tablets that the patient should have returned (based on the number 
of days since the previous visit).  The number of tablets dispensed, the number returned, and the 
number expected to be returned will be recorded in the patient’s record.  An assessment of 
medication adherence should be done by the study staff to ensure that the patient understands all 
dosing instructions and is taking the medication as prescribed.  If it is found that the patient is not 
taking the study medication as prescribed, the patient will be re-counseled on correct 
administration, and this should be noted in the patients’ record, and discussed with the medical 
monitor, if necessary.  
If the patient fails to return all unused study drug as expected, the patient should be questioned 
regarding the reason for the lower than expected tablet number and about potential misuse, abuse 
or diversion.  In situations where more than 2 tablets per week cannot be accounted for, the 
investigator will be asked to evaluate the situation, and a written summary should be added to the 
source and entered onto the case report form (CRF).  In addition, the medical monitor should be 
contacted any time a patient requests replacement medication for any reason (e.g., loss of bottles 
or damage to study drug).  Situations where replacement drug is requested, or when more than 2 
tablets per week cannot be accounted for, should be recorded as deviations.   
All study medication, including partial and empty bottles, must be maintained at the study site 
until Tonix or its designee verifies drug accountability and provides instruction for the 
destruction or the return of the investigational product to the Sponsor’s drug distribution depot.  
Tonix or their designee will perform drug accountability which entails reconciliation between the 
amount of drug shipped to the study site, study drug assigned and dispensed to the patient 
(including returned unused assigned study drug), and study supplies that were never dispensed 
and/or assigned to patients.  
 

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9. 
STUDY VISITS AND PROCEDURES 
The overall and detailed schedule for study procedures and visits is provided in Appendix 1. 
9.1. 
Visit 1 – Screening/Baseline (Week 0, Day 1) 
9.1.1. 
Informed Consent 
Before the potential patient has undergone any study-related screening procedures, the nature of 
the study and the potential risks associated with it will be explained to the patient, and the patient 
will be given an opportunity to ask questions to his or her satisfaction.  After all questions are 
answered, but before proceeding further, the patient must read and sign a written informed 
consent form.  This signed informed consent form will be retained in the Investigator’s study 
file, and the date the patient signed the form will be entered into the CRF.  The patient will be 
provided with a copy of his or her signed and dated informed consent form.  The patient will be 
required to sign all updated informed consents. 
Separate written, signed informed consent must be obtained if the patient is to participate in the 
optional pharmacogenomic assessment.   
 
9.1.2. 
Screening Overview 
The first study visit, Visit 1, will be where the study is explained to the prospective study patient, 
where written informed consent will be obtained and documented, and where protocol-specified 
study procedures and assessments will be completed.   
For patients enrolling into this study from the 12-week open label extension study, P303, the 
P306 Baseline Visit (Visit 1) date is intended to be the same date as the final visit of the 12-week 
open label extension study, P303.  However, if there are extenuating circumstances, Visit 1 of 
P306 may occur within fourteen days of their final visit in P303 without repeating baseline 
assessments.   If more than fourteen days elapse between the final visit of P303 and start of the 
P306 study, medical monitor approval will be required and baseline assessments will need to be 
repeated.   
For patients enrolling directly from the double-blind lead-in study, P301, all Visit 1 assessments 
will be performed.  These patients are also expected to enter the P306 study at the same time as 
their final P301 visit; however, if there are extenuating circumstances, then Visit 1 of P306 may 
occur within fourteen days of their final P301 visit.    
Once the patient has provided written informed consent to participate and has met all relevant 
inclusion criteria, this patient is eligible to begin the open-label treatment period, starting at 
bedtime on the day of enrollment.  The patient should be dispensed three bottles of TNX-102 SL 
tablets, along with dosing and storage instructions.  The end-of-study information collected at the 
final visit of the 12-week open label extension study P303, or the Visit 1 assessments completed 
as part of this protocol, will be considered the baseline values for Study P306. 
9.1.3. 
Patient Numbering 
All patients who participated in the double-blind lead-in HONOR study will retain their original 
concatenated 6-digit site-patient number, i.e., all patients entering P306.   

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9.1.4. 
Pharmacogenomic Assessment  
Patients should be offered the opportunity to participate in the pharmacogenomic assessment as 
soon as Protocol Amendment 01 has been approved and implemented at the clinical site.  The 
blood draw for this assessment is not tied to any specific visit; instead, it should be obtained after 
the patient has reviewed and signed the separate pharmacogenomic testing informed consent 
form, irrespective of the visit at which the consent is signed.    
9.1.5. 
Visit 1 Baseline Assessments/Procedures (Week 0) 
 
The following assessments/procedures will be completed at Visit 1.   
 
For all patients: 
▪ Obtain written informed consent to participate 
▪ Inclusion criteria 
▪ Review and transcribe new concomitant medications as well as those which are to be 
continued from the double-blind lead-in HONOR study or the 12-week open-label 
extension study P303 
▪ Review and transcribe new AEs as well as those which are ongoing from the double-
blind lead-in HONOR study or the 12-week open-label extension study P303 
 
For patients enrolling from the double-blind lead-in study, P301/HONOR only (or  patients 
rolling over to study P306 more than 14 days after the final visit of the 12-week open-label 
extension study P303): 
▪ Obtain vital signs, including weight. The height collected at baseline from the lead-in 
study will be utilized for body mass index (BMI) calculations in this study. 
▪ Perform a visual exam of the oral cavity  
▪ Have the patient complete the PROMIS-Sleep Disturbance scale and the SDS.  
Review each scale for completeness once done.  
▪ Have the patient complete the BDI-II  
▪ Conduct the C-SSRS after reviewing the results of the BDI-II 
▪ Draw blood for clinical laboratory testing  
▪ Review patient’s lifetime psychiatric treatment history, demographic information and 
medical history to ensure the information recorded during the double-blind lead-in 
study is accurate and complete, as it will also be included in the extension study’s 
database.   
Only those patients meeting all of the inclusion criteria will be eligible to continue.   
 
For all patients: 
 
After all study requirements for Visit 1 of P306 have been fulfilled, the patient will:  

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▪ Be dispensed 3 bottles of TNX-102 SL tablets and be instructed to begin dosing with 
study medication at bedtime, starting the evening of Visit 1;  
▪ Receive instruction regarding proper sublingual dosing technique and the time of 
expected dosing; and  
▪ Schedule the telephone Visit 2 (for patients enrolled from the double-blind lead-in 
study, P301/HONOR, only) and receive an appointment to return to the clinic for 
Visit 3. 
9.2. 
Visit 2 (Telephone Visit: Week 2) 
For patients enrolled from the double-blind lead-in study, P301/HONOR only:  Visit 2 will be 
done as a telephone call to the patient and should be conducted after 2 weeks of treatment, on 
Day 14 ± 3 days. 
The following steps should be completed: 
▪ Assess changes in concomitant medications 
▪ Assess study drug compliance based on patient verbal report 
▪ Assess occurrence of AEs, including any oral AEs and whether an unscheduled visit 
is indicated for an examination of the oral cavity 
▪ Review patient instructions regarding drug dosing and storage  
▪ Administer the ‘Since Last Visit’ C-SSRS telephonically 
9.3. 
Visits 3, 4, and 5 (Weeks 7, 16, and 28) 
These visits are conducted after 7, 16, and 28 weeks (± 7 days) of treatment respectively.  The 
following assessments and procedures are to be conducted at each of these visits in the following 
general order:  
▪ Collect returned study medication from patient and perform drug accountability 
▪ Assess study drug compliance  
▪ Assess for changes in concomitant medications 
▪ Assess for occurrence of AEs  
if any oral AEs have been reported (other than numbness, tingling or bitter taste), 
perform and document an examination of the oral cavity  
▪ Have the patient complete the “baseline” PCL-S (Visit 5 only) 
▪ Have the patient complete the PROMIS-Sleep Disturbance Scale and the SDS.  
Review each scale for completeness once done. 
▪ Have the patient complete the BDI-II 
▪ Conduct the C-SSRS after reviewing the results of the BDI-II  
▪ Vital signs and weight 

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▪ Draw blood for clinical laboratory tests (Visit 5 only) 
▪ Urine pregnancy test (for women of child-bearing potential) 
▪ Inspect the oral cavity and document findings, if any (Visit 5 only) 
▪ Conduct the CGI-I, using the P306 baseline visit as comparison  
▪ Dispense 4 new bottles of TNX-102 SL tablets at Week 7 (Visit 3).  At Weeks 16 
(Visit 4) and 28 (Visit 5), dispense 5 new bottles. 
 
Review patient instructions regarding drug dosing and storage, and schedule appointment for 
next clinic visit.  
 
9.4. 
Visit 6 (Week 40) 
 
Visit 6 is to be conducted after 40 weeks (±7 days) of treatment in the extension study. At this 
visit, the patient (Track A only) will return all remaining study drug and the following 
assessments and procedures are to be completed in the following general order:  
▪ Collect returned study medication from patient and perform drug accountability 
▪ Assess study drug compliance  
▪ Assess for occurrence of AEs  
▪ Assess for changes in concomitant medications  
▪ Obtain vital signs including weight 
▪ Track A patients only: Draw blood for clinical laboratory tests 
▪ For women of child-bearing potential, conduct urine pregnancy test 
▪ Track A patients only: Inspect the oral cavity and document findings, if any 
▪ Have the patient complete the PCL-S 
▪ Have the patient complete the PROMIS-Sleep Disturbance Scale and SDS 
▪ Have the patient complete the BDI-II 
▪ Conduct the C-SSRS after reviewing the results of the BDI-II 
▪ Conduct CGI-I comparing to the P306 baseline 
▪ Track B patients only: Dispense 5 new bottles of TNX-102 SL tablets  
 
9.5. 
Visit 7 (Week 52) 
 
Track B patients only: Visit 7 is to be conducted after 52 weeks (±7 days) of treatment in the 
extension study. At this visit, the patient will return all remaining study drug and the following 
assessments and procedures are to be completed in the following general order:  
▪ Collect returned study medication from patient and perform drug accountability 

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▪ Assess study drug compliance  
▪ Assess for occurrence of AEs  
▪ Assess for changes in concomitant medications  
▪ Obtain vital signs including weight 
▪ Draw blood for clinical laboratory tests 
▪ For women of child-bearing potential, conduct urine pregnancy test 
▪ Inspect the oral cavity and document findings, if any 
▪ Have the patient complete the PCL-S 
▪ Have the patient complete the PROMIS-Sleep Disturbance Scale and SDS 
▪ Have the patient complete the BDI-II 
▪ Conduct the C-SSRS after reviewing the results of the BDI-II 
▪ Conduct CGI-I comparing to the P306 baseline 
 
9.6. 
Early Termination (ET) 
In accordance with the Declaration of Helsinki, patients have the right to withdraw from the 
study at any time for any reason, and they will be advised of this right.  The investigator and 
Tonix also have the right to remove patients from the study.  Specific reasons for removal of a 
patient from the study could include, but are not limited to: 
▪ An AE 
▪ An illness that, in the judgment of the investigator or Tonix, might invalidate the 
study results or place the patient at risk 
▪ The request of the patient, investigator, or Tonix, whether for administrative or other 
reasons 
▪ Pregnancy 
Patients who wish to terminate their participation in the study should be instructed to come to the 
clinic for an Early Termination Visit.  The purpose of the Early Termination visit is to obtain 
critical information about the patient’s participation, and should be scheduled preferably before 
there has been a substantial lapse in study medication usage.  However, even if there has been a 
medication lapse, the patient should be encouraged to return to the clinic for this visit, and should 
be instructed to return all remaining study medication.  
The following assessments and procedures are completed at this visit in the following general 
order:  
▪ Collect returned study medication from patient and perform drug accountability 
▪ Assess study drug compliance  
▪ Assess for occurrence of AEs  

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▪ Assess for changes in concomitant medications  
▪ Obtain vital signs including weight 
▪ Draw blood for clinical laboratory tests 
▪ For women of child-bearing potential, conduct urine pregnancy test 
▪ Inspect the oral cavity and document findings, if any 
▪ Have the patient complete the PROMIS-Sleep Disturbance Scale and SDS 
▪ Have the patient complete the BDI-II 
▪ Conduct the C-SSRS after reviewing the results of the BDI-II 
▪ Conduct CGI-I comparing to the P306 baseline 
Once these assessments have been completed, the patient may be discharged from the study, 
provided there is no need for additional follow-up to continue to monitor an AE or other 
condition. 
9.7. 
Unscheduled Visits 
Patients may need to be seen at other times than the scheduled study visits for additional safety 
assessments or to follow-up, as medically necessary, on clinical laboratory, physical 
examination, or other findings.  In addition, if a patient calls between scheduled visits to report a 
visible lesion in the oral cavity or other concerning oral cavity AE, the patient should be asked to 
return to the clinic as soon as possible for an unscheduled oral cavity examination.  Unscheduled 
examinations are NOT required for reports of oral numbness, tingling, bitter taste, or for other 
mild or transient AEs that are not concerning to the patient.  If an additional study visit occurs, 
the date and nature of the visit will be documented in the CRF and in the source documents.  The 
patient should be advised to bring study medication with them to the unscheduled visit. 

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10. 
STUDY ASSESSMENTS 
10.1. 
Screening Assessments 
The results of the screening assessments should be reviewed to ensure that the patient continues 
to satisfy all entry criteria and otherwise remains a satisfactory patient for the extension study.  
Laboratory assessments obtained at the final visit of the double-blind lead-in HONOR study or 
the 12-week open-label extension study P303 will not be available prior to the patient’s entry 
into the extension study, but should be reviewed within 7 days when they become available, to 
ensure the patient’s ongoing well-being. 
10.2. 
Efficacy Assessments 
A secondary objective of this study is to evaluate the long-term effect of TNX-102 SL and these 
endpoints are derived from both clinician-administered and subjective patient-completed 
assessments.  The clinician-administered assessments must be administered by qualified and 
trained individuals at each clinical site.  Study specific training will be required before new staff 
that were not trained for the lead-in study are allowed to administer these scales.  In an attempt to 
minimize variability in responses of a given patient over time, it is important that the same rater 
administer the scales to a given patient throughout the study as much as possible.  It is also 
important that the assessments, including those that are patient-completed, be conducted in the 
specified order, according to specific instructions, and in a setting where the patient has minimal 
distractions and sufficient time to complete them.  After completion of these assessments, the 
study coordinator should review the responses for completeness with the patient.  
10.2.1. 
Clinical Global Impression of Improvement (CGI-I) 
The CGI-I is a commonly used clinician-rated scale designed to assess overall clinical 
improvement (change) since baseline.  The CGI-I will be completed at each in-clinic visit after 
baseline.  It will be the responsibility of the Principal Investigator or his qualified designee to 
assess change in the subject’s overall status. 
10.2.2. 
Sheehan Disability Scale (SDS) 
The SDS scale is a self-report questionnaire that was designed to assess the subject’s view of the 
degree to which symptoms have disrupted work, social life/ leisure activities, and family life/ 
home responsibilities during the past week.  In addition, the SDS asks the subject to provide the 
number of days or work lost as well as unproductive days.  The SDS will be administered at each 
in-clinic visit. 
10.2.3. 
PROMIS Sleep Disturbance Scale  
PROMIS refers to the Patient-Reported Outcome Measurement Information System 
(www.nihpromis.org), an NIH-funded initiative to develop instruments to be used across chronic 
conditions.  The PROMIS scale for sleep disturbance (form 8a) will be administered at all in-
clinic visits. 

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10.2.4. 
Beck Depression Index (BDI-II) 
BDI-II refers to the patient-rated assessments of depressive symptomology.  The BDI-II will be 
administered at all in-clinic visits.  Each patient’s response to the BDI suicidality question (item 
9) should be reviewed and compared to the C-SSRS responses to ensure careful assessment of 
any suicidal ideation and resolution of any discrepancies between the self-reported BDI-II and 
the C-SSRS interview. 
10.2.5. 
PTSD Checklist-Specific Version (PCL-S) 
Developed by the National Center for Posttraumatic Stress Disorder, the PCL-S is a 17-item self-
report measure reflecting DSM-IV symptoms of PTSD. The PCL-S aims to link symptom 
endorsements to a specified event or stressful experience, which for P306 has been identified by 
the subject as their Index Trauma during the lead-in double blind study (TNX-CY-P301). 
Respondents rate each item from 1 ("not at all") to 5 ("extremely") to indicate the degree to 
which they have been bothered by that particular symptom over the past month.  
In addition, the long-term safety of TNX-102 SL on PTSD based on PCL-S completed by 
patients in Visit 5 (Week 28) and Visit 6 (Week 40) and Visit 7 (Week 52 for patients enrolled 
under Track B), is assessed with this scale. The mean change in PCL-S total score and PCL-S 
clusters scores from Visit 5 (Week 28) to Visit 6 (Week 40), or to Visit 7 for Track B patients 
will detect any potential worsening in total PTSD score or symptoms clusters in the final 12-
weeks, or 24-weeks for Track B patients, of the study.  Since PCL-S is added to the study when a 
significant number of patients have passed the Visit 4 (Week 16 time point, Visit 5 (Week 28) is 
chosen as the “baseline” for PCL-S in order to capture the vast majority of the patients who 
enrolled in the study from its beginning. 
10.3. 
Pharmacogenomics Testing 
For pharmacogenomic analysis, a single blood draw collected in two PAXgene DNA tubes will 
be obtained from each patient after they have provided separate written, signed informed consent 
for pharmacogenomic analysis.  The purpose of this testing is to allow exome sequencing and 
analysis for genetic variants related to treatment response to TNX-102 SL. It is presumed that 
unused sample will be stored up to fifteen years, and potentially utilized to develop a 
pharmacogenomic test for determining likelihood of treatment response to TNX-102 SL.  A 
decision not to participate in optional pharmacogenomic testing will not affect the patient’s 
eligibility for the main study. Patients have the right to stop participating at any time during the 
study or during the time of sample storage, and, if a patient decides to withdraw from the 
pharmacogenomics portion of this study, any remaining sample will be destroyed and not used 
for further research.  Data collected before a patient’s withdrawal from the pharmacogenomics 
portion of this study will remain in the research database. 
10.4. 
Safety Parameters  
Safety will be assessed by evaluation of adverse events, responses on the C-SSRS, clinical 
laboratory tests, examinations of the oral cavity, vital signs, weight, patient-rated assessments of 
depressive symptomology (BDI-II) and PTSD symptomology (PCL-S).  

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10.4.1. 
Adverse Events (AEs)  
Patients will be monitored for AEs throughout the study, from the time the patient signs an 
informed consent onward.  AEs that are spontaneously reported, elicited or observed are to be 
recorded on the CRF with the date, time of onset, date and time of resolution, severity, 
seriousness, causality (relationship to study medication), actions required, and outcome.  
To elicit AEs, non-leading, simple questions with minimal connotations should be used as the 
initial questions at all evaluation points during the study.  Examples of these questions can be:  
▪ How have you felt since your last visit?  
▪ Have you had any health problems since your last visit?  
If an AE occurs, the investigator will institute support and/or treatment as deemed appropriate.  
If a non-serious AE is unresolved on the last day of the study, an effort should be made to follow 
up until the AE is resolved or stabilized, the patient is lost to follow-up, or there is some other 
resolution of the event.  
There are many symptoms associated with PTSD that can vary in intensity and frequency over 
time.  Only symptoms that significantly worsen or become more frequent, and in the opinion of 
the patient are outside of their normal experience, should be reported as adverse events.  
If a patient reports an oral adverse event other than numbness, tingling or bitter taste, the 
Investigator should examine the oral cavity to confirm presence or absence of any lesion or other 
abnormality, and document the exam.  Additional details related to onset, duration, severity and 
reversibility of the oral event will also be documented.  
10.4.1.1. Columbia-Suicide Severity Rating Scale (C-SSRS)  
The C-SSRS is a clinician-administered interview developed by researchers at Columbia 
University to assess suicide risk and to track suicidal ideation and behavior during clinical trials.  
This scale is intended to be administered by individuals who have received training in its 
administration.  The questions contained in the Columbia-Suicide Severity Rating Scale are 
suggested probes.  Ultimately, the determination of the presence of suicidal ideation or behavior 
depends on the judgment of the individual administering the scale.  
The “since last visit” version of the C-SSRS will be completed at all study visits.  Note that if 
there has been a significant change in responses to this scale indicative of increased suicide risk, 
appropriate intervention should be prescribed Section 10.4.1.2 and an AE should be recorded.   
The patient’s response to BDI-II item 9 (suicidal ideation) should be reviewed prior to 
conducting the C-SSRS at the in-clinic visits to ensure the patient’s responses are consistent 
between the BDI and the C-SSRS (and/or the reason for any inconsistency documented in the 
patient’s chart).        
10.4.1.2. Safety Planning Intervention (SPI)  
The C-SSRS is completed at every visit in order to assess for changes in suicidality during the 
study.  If a patient scores a 4 or 5 on the Suicidal Ideation section of the C-SSRS at a clinic visit 
following enrollment, the patient should be withdrawn from the study and referred for 
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If a patient scores a 2 or 3 on the Suicidal Ideation section of the C-SSRS at any visit, the 
investigator should consider the implementation of a Safety Planning Intervention (SPI).  The 
recommended SPI for this study is the plan developed by Barbara Stanley, PhD and Gregory 
Brown, PhD which has been adopted by the US Veteran’s Administration (VA) (Stanley & 
Brown, 2012).  The VA SPI is a brief clinical intervention aimed at mitigating suicide risk.  It 
consists of a written, prioritized list of coping strategies and sources of support that patients can 
use to alleviate a suicidal crisis.  Sites may use an internally-developed SPI if similar in scope 
and purpose to the VA SPI.  
10.4.1.3. Visual Examination of Oral Cavity  
A visual examination of the oral cavity should be done at Baseline/Visit 1 (or the Week 12 Visit 
of the 12-week open label study) and after 28 weeks (Visit 5) and 40 weeks (Visit 6) for Track A 
patients, or after 52 weeks of treatment (Visit 7) for Track B patients, and/or at ET.  In addition 
to these regularly scheduled examinations, a visual inspection of the oral cavity (including the 
sublingual area) should be done any time a patient reports a lesion or other finding in the oral 
cavity other than numbness, tingling or bitter taste, in order to document the presence or absence 
of any visible abnormalities.  Additional details related to onset, duration, severity and 
reversibility of oral events will also be documented in the CRF.  
10.4.1.4. Vital Signs  
Vital signs (sitting blood pressure and heart rate, respiratory rate, oral temperature, and weight) 
will be assessed at Visits 1, 3, 4, 5, 6 and 7 (Visit 7 for Track B patients only).  Height will be 
transferred from the lead-in study database for BMI calculations (done at Baseline and Visit 6 for 
Track A patients or Visit 7 for Track B patients).  
10.4.1.5. Clinical Laboratory Assessments  
The clinical laboratory evaluations to be performed in this study are listed in Table 2.  All tests 
will be performed at Baseline/Visit 1 (or the Week 12 Visit of the 12-week open label HONOR 
study), after 28 weeks (Visit 5) and after 40 weeks of treatment (Visit 6) for Track A patients, or 
after 52 weeks of treatment (Visit 7) for Track B patients, or ET.  
With the exception of the urine pregnancy tests, all clinical laboratory evaluations will be 
analyzed via a central clinical laboratory, and information regarding appropriate sample volume, 
collection tubes, sample labeling and handling, and shipment will be provided in a study manual. 
Each clinically significant abnormal laboratory value or other clinically meaningful abnormality 
should be followed until the abnormality resolves or until a decision is made that it is not likely 
to resolve.  If such abnormalities do not return to normal within a reasonable period, their 
etiology should be identified and Tonix or designee should be notified.  Treatment-emergent 
clinically significant abnormalities in laboratory values will be recorded as AEs.  
 
Table 2:  
Clinical Laboratory Assessments  
Clinical chemistry 
Hematology  
Alanine aminotransferase (ALT)  
Hematocrit  

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Alkaline phosphatase  
Hemoglobin  
Aspartate aminotransferase (AST)   
MCH concentration (MCHC)  
Bilirubin (total)  
Mean corpuscular hemoglobin (MCH)  
Blood urea nitrogen (BUN)  
Mean corpuscular volume (MCV)  
Calcium  
Platelet count  
Chloride  
Red blood cell (RBC) count  
Cholesterol (total)  
White blood cell (WBC) count differential  
Creatinine kinase (CK)  
      Neutrophil count (absolute and %)  
Creatinine  
      Lymphocyte count (absolute and %)  
Glucose  
      Monocyte count (absolute and %)  
Phosphorus  
      Eosinophil count (absolute and %)  
Potassium  
      Basophil count (absolute and %)  
Protein (albumin and total)  
WBC count  
Sodium  
  
Urine Pregnancy Test (qualitative 
dipstick)a  
   
Pharmacogenomic testing (optional; 
can be obtained at any visit, including 
an early termination visit) 
 
a Pregnancy testing for females of child-bearing potential only.  A positive pregnancy test mandates withdrawal 
from the study (all visits). 
11. 
DEFINITIONS, RECORDING, AND REPORTING OF ADVERSE 
EVENTS AND PREGNANCY 
11.1. 
Definition of Adverse Events 
According to International Council on Harmonisation (ICH) guidance E2A, Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting, an AE is any untoward 
medical occurrence in a patient or clinical investigation patient administered a pharmaceutical 
product and which is not necessarily required to have a causal relationship with this treatment.  
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
A newly-emergent adverse event (NEAE) is defined as any new AE that starts after the patient’s 
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week open-label extension study and which then exhibits an increase in severity, frequency or 
relationship after the patient’s participation in P306 has begun.  NEAEs and “All AEs” will be 
tallied by System Organ Class (SOC) and preferred terms.  AEs that are ongoing at the time of 
the patient’s baseline visit for P306 but which resolve, or persist without change in severity, 
frequency or relationship to study drug during the extension study, will be included in the tally of 
all AEs.   
11.2. 
Adverse Event Recording 
11.2.1. 
Coding the Adverse Event 
Standard medical terminology should be used in describing AEs.  Medical Dictionary for 
Regulatory Activities (MedDRA)® will be used as the standard coding dictionary for AEs and in 
describing the patient’s medical history, and the World Health Organization (WHO) Drug 
Dictionary will be used to code concomitant medications.  Informal descriptions should be 
avoided. 
11.2.2. 
Severity of Adverse Event 
AEs should be graded as mild, moderate, or severe using the following definitions. 
• Mild: Awareness of signs or symptoms, but easily tolerated and of minor irritant type 
causing no loss of time from normal activities.  Symptoms do not require therapy or a 
medical evaluation; signs and symptoms are transient. 
• Moderate: Events introduce a low level of inconvenience or concern to the 
participant and may interfere with daily activities, but are usually improved by simple 
therapeutic measures; moderate experiences may cause some interference with 
functioning. 
• Severe: Events interrupt the participant’s normal daily activities and generally require 
systemic drug therapy or other treatment; they are usually incapacitating. 
To make sure there is no confusion or misunderstanding of the difference between the terms 
“serious “and “severe,” which are not synonymous, the following note of clarification is 
provided.  The term “severe” is often used to describe the intensity (severity) of a specific event 
(as in mild, moderate, or severe myocardial infarction); the event itself, however, maybe of 
relatively minor medical significance (such as severe headache).  This is not the same as 
“serious,” which is based on patient/event outcome or action criteria usually associated with 
events that pose a threat to a patient's life or functioning.  Seriousness (not severity) serves as a 
guide for defining regulatory reporting obligations. 
11.2.3. 
Relationship of Adverse Events to Study Drug 
The investigator will assess the potential relationship of the AE to study drug using the following 
descriptions. 
• Not Related: This category applies to an AE that is clearly not related to the 
investigational agent/procedure, beyond a reasonable doubt.  That is, another cause of 
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inconsistent with the onset of the event and the administration of study drug and/or a 
causal relationship is considered biologically implausible. 
• Unlikely Related: This category applies to an AE that could reasonably be considered 
caused by something else, and where there is no known or expected response pattern 
to the suspected study drug. 
• Possibly Related: This category applies to an AE that follows a reasonable temporal 
sequence from administration of the study drug and that follows a known or expected 
response pattern to the suspected study drug, but that could readily have been 
produced by a number of other factors. 
11.3. 
Serious Adverse Events (SAEs) and Serious Adverse Drug Reactions 
Any SAE that occurs at any time during the study, or within 28 days after the patient’s last 
exposure to study drug, including a clinically significantly abnormal laboratory test result that is 
considered serious, must be reported to Tonix or its designee(s) so that Tonix may comply with 
regulatory obligations.  If the SAE is life-threatening or fatal, it must be reported to Tonix or its 
designee(s) immediately, by email or telephone.  For these and all other SAEs, an SAE report 
form must be completed and sent by facsimile or email to Tonix or its designee(s) within 24 
hours of the site’s initial awareness of the event.  These requirements apply equally to all 
patients, regardless of the study phase or the at-risk patient’s treatment assignment. 
A serious adverse event (experience) or reaction is any untoward medical occurrence that, at any 
dose: 
• Results in death, 
• Is life-threatening, 
• Requires in-patient hospitalization or prolongation of existing hospitalization, 
• Results in persistent or significant disability/incapacity, 
• Is a congenital anomaly/birth defect, or 
• Is an important medical event 
NOTE: The term “life-threatening” in the definition of “serious” refers to an event in which the 
patient was at risk of death at the time of the event.  It does not refer to an event that 
hypothetically might have caused death if it were more severe. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the other outcomes listed in the definition above.  These should 
also usually be considered serious.  Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization, or development of drug dependency or drug abuse. 
A death occurring during the study or reported to the Investigator after study participation (no 
required post-study time limit) must be reported to Tonix or its designee(s) immediately, whether 
or not it is considered treatment-related.  Initial SAE reports must be followed by detailed 

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descriptions.  These should include copies of hospital case records and other documents when 
requested.  The Contract Research Organization (CRO) will confirm via email or facsimile when 
it has received SAE documentation.  If such confirmation is not received at the site in a timely 
manner, it is then the responsibility of the site to contact the CRO to ensure that the SAE 
documentation was indeed received by the CRO.   
The Investigator or other study personnel must immediately inform one of the Tonix Medical 
Monitors by phone or email of any AE considered serious or otherwise significant, as described 
above.  In addition, a completed SAE report form must be submitted to
 
 within 24 hours of the site’s initial awareness of the event. 
 
Contact information for the Medical Monitors is provided below: 
 
 
For questions pertaining to the reporting of SAEs or the completion of SAE documentation, 
site personnel should call the 
 
The investigator, or the sponsor or designee in the case of a central Institutional Review Board 
(IRB), also must notify the Ethics Committee (EC)/IRB of the occurrence of the SAE, in writing, 
as soon as is practicable and in accordance with local law.  A copy of this notification must be 
provided to Tonix or its designee. 
In the event of an SAE that meets the criteria for expedited reporting, an Investigational New 
Drug (IND) Safety Report will be prepared for submission to the FDA. 

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11.4. 
Pregnancy 
The active pharmaceutical ingredient in TNX-102 SL 2.8 mg tablets is cyclobenzaprine HCl, 
which is in Pregnancy Category B (See Appendix 3 for AMRIX® Package Insert).  All 
pregnancies occurring during the study (after exposure to study drug) or within 30 days after 
discontinuation of study drug must be followed until resolution (i.e., birth or voluntary or 
spontaneous termination of the pregnancy).  Any patient found to be pregnant at any time during 
the study will be withdrawn from the study immediately.  Any pregnancy outcome that meets the 
criteria for an SAE will be reported as an SAE. 

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12. 
STATISTICS 
A description of any statistical analyses to be performed will be provided in a statistical analysis 
plan (SAP), which will be finalized prior to database lock.    
12.1. 
Evaluation of Safety  
Safety data will be summarized as a single treatment group receiving 1 or more doses of TNX-
102 SL (patients that have taken only 1 tablet of TNX-102 SL will be included).   
Safety will be assessed by the monitoring and recording of AEs, clinical laboratory tests, vital 
signs, visual examination of the oral cavity findings, the monitoring of suicidality using the 
Columbia C-SSRS scale, and patient-rated assessments of depressive symptomology (BDI-II) 
and PTSD symptomology (PCL-S). 
AEs will be coded using the MedDRA and will be summarized overall and by preferred term and 
SOC. AEs will also be summarized by severity and relationship to study drug. SAEs and AEs 
leading to discontinuation of study drug will also be summarized.  
Actual values and changes from the extension study baseline values for clinical laboratory test 
results and vital sign measurements will be summarized at endpoint using descriptive statistics 
(n, mean, standard deviation (SD), median, minimum, and maximum).  Laboratory values will be 
displayed in the data listings along with corresponding normal ranges, and those that are outside 
the normal range will be flagged.   
Based on the C-SSRS results, the frequency and severity of suicidal ideation and behavior will 
be tabulated at each time point.  The number of patients with baseline and treatment-emergent 
suicidal ideation and/or suicidal behavior or self-injurious behavior, based on the C-SSRS, will 
be summarized by treatment group. 
All data gathered will be listed by patient and parameter, and clinically significant abnormalities 
should be recorded as AEs. AEs of special interest indicating potential abuse and dependency 
will be evaluated and summarized as described in the Statistical Analysis Plan. 
12.2. 
Evaluation of Efficacy  
As this is a long-term safety study, minimal conclusions will be available concerning long-term 
efficacy. The efficacy analyses will focus on durability of the response achieved prior to entry into 
this extension study, based on the CGI-I for patients in Track A and for patients on active drug in 
the lead-in HONOR study or the P303-early-terminated patients (due to IA results) who were on 
placebo in P301 in Track B. In addition, durability of response for both Track A and B patients 
will be assessed by measuring the change in PCL-S scores from Visit 5 (Week 28) to Visit 6 (Week 
40) in order to detect any potential worsening in PTSD symptoms as a result of longer term use of 
TNX-102 SL 5.6 mg. For Track B patients, an additional Visit 7 (Week 52) PCL-S assessment 
with be available for subset analysis of durability of response. 
12.3. Estimate of Sample Size  
No sample size calculations were made for this study as it is a follow-on, open-label study.  The 
sample size for this study will depend upon the number of patients who participate in the lead-in 

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HONOR study, remain eligible for entry, and indicate willingness to participate in this extension 
study.  
12.4. 
Assessment of Demographic and Baseline Characteristics and 
Patient Disposition 
For categorical variables, frequencies and percentages will be presented. Continuous variables 
will be summarized using descriptive statistics (n, mean, median, SD, minimum, and maximum).  
Demographic and baseline characteristic variables will be summarized based on the data 
obtained at the screening visit from the lead-in HONOR study. The number of patients who 
enroll in the study and the number and percentage of patients in each analysis population who 
complete the treatment period will be presented. The frequency and percentage of patients who 
withdraw from the study, along with the reason for withdrawal or discontinuation, will also be 
summarized.  

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13. 
PROCEDURES FOR MODIFYING THE PROTOCOL OR 
TERMINATING THE STUDY 
13.1. 
Protocol Modifications and Deviations 
The investigator will make all reasonable efforts to comply with the written protocol and 
protocol amendments.  All protocol modifications must be reviewed and approved by the 
appropriate EC/IRB before the revised protocol can be implemented.  Emergency revisions that 
eliminate an apparent hazard to patients do not require preapproval by the EC/IRB.  However, 
the EC/IRB must be notified, in writing, as soon as possible after the modification has been 
made.  A copy of this communication must be forwarded to Tonix. 
13.2. 
Study Termination 
The study may be prematurely terminated at any time at the discretion of Tonix, its designee, or 
the principal investigator.  Should premature termination be considered necessary, written 
notification documenting the reason for study termination will be provided, and specific 
procedures for termination will be arranged.  Circumstances that may warrant premature study 
termination include, but are not limited to, the following. 
• Determination of unexpected, significant, or unacceptable risk to patients 
• Failure to enter patients at an acceptable rate 
• Insufficient adherence to the requirements of the protocol 
• Insufficient provision of complete and evaluable data 
• Plans to modify, suspend, or discontinue development of the study drug 
In the event that the study is terminated prematurely, all study materials must be returned to 
Tonix or its designee. 

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14. 
ETHICAL CONSIDERATIONS 
14.1. 
Ethical Conduct of the Study 
This protocol is written in accordance with the principles established by the 18th World Medical 
Assembly General Assembly (Helsinki, 1964CI) and amendments and clarifications adopted by 
subsequent General Assemblies.  The investigator will make sure that the study described in this 
protocol is conducted in full conformance with those principles, the protocol, current FDA 
regulations, ICH GCP guidelines, Good Laboratory Practices (GLP) guidelines, local ethical and 
regulatory requirements, including the Federal Food, Drug and Cosmetic Act, US applicable 
Code of Federal Regulations (CFR) (title 21), any EC requirements relative to clinical studies.  
As required by the US FDA, the study drug may not be shipped to any participating investigator 
until the requisite study documentation has been submitted to the IND. 
Should a conflict arise, the investigator will follow whichever law or guideline affords the 
greater protection to the individual patient.  The investigator will also make sure he or she is 
thoroughly familiar with the appropriate administration and potential risks of administration of 
the study drug, as described in this protocol and the Investigator’s Brochure, prior to the 
initiation of the study. 
14.2. 
Ethics Committee/Institutional Review Board (EC/IRB) Review 
The EC/IRB must be a properly constituted board or committee operating in accordance with 21 
CFR Part 56, “Institutional Review Boards.”  This protocol, any protocol amendments, the 
associated informed consent forms, and the informed consent procedures must be submitted to 
the EC/IRB for review and approved before the enrollment of any patient into the trial. 
All types of patient recruitment or advertising information must be submitted to Tonix or its 
designee and to the EC/IRB for review and approval prior to implementation.  EC/IRB approval 
of any protocol amendments must be received before any of the changes outlined in the 
amendments are put into effect, except when the amendment has been enacted to eliminate a 
potential hazard to study patients.  In such cases, the chair of the EC/IRB should be notified 
immediately and the amendment forwarded to the EC/IRB for review and approval. 
14.3. 
Written Informed Consent 
It is the responsibility of the investigator to obtain signed written informed consent from each 
potential study patient prior to the conduct of any screening or other study procedures.  This 
written informed consent will be obtained after the methods, objectives, and potential risks of the 
study have been fully explained to the potential patient.  The investigator must explain to each 
patient that he or she is completely free to refuse to enter the study or to withdraw from it at any 
time.  NOTE:  Patients on antidepressant therapy should be warned of a potential serious drug 
interaction and should be advised to contact their study site immediately if they experience any 
symptoms that might represent possible serotonin syndrome, including fever, confusion or 
agitation, hallucinations, sweating, high or low blood pressure, rapid heart rate, tremor, muscle 
rigidity or nausea, vomiting or diarrhea. 
The method of obtaining and documenting informed consent and the contents of the ICF will 
comply with ICH GCP guidelines, the requirements of 21 CFR Part 50, “Protection of Human 

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Patients,” the HIPAA regulations, and all other applicable regulatory requirements.  A properly 
executed written ICF shall be read, signed, and dated by each patient prior to entering the trial or 
prior to performing any study procedure.  The original signed and dated ICF will be kept on file 
at the study site.  Patients will be given a copy of the signed ICF and will be informed of any 
new developments during the course of the study that might influence their continued 
participation in the study. 
The investigator or a qualified designee will be available to answer each patient’s questions 
throughout the study, and all questions must be answered to the patient’s satisfaction.  If the 
protocol is amended and a revised ICF is introduced during the study, each patient’s further 
consent must be obtained.  The new version of the ICF must be approved by the EC, prior to 
subsequently obtaining each patient’s consent. 
Receipt of written informed consent will be documented in each patient’s or potential patient’s 
CRF.  The signed ICF must remain in each patient’s study file and must be available for 
verification by study monitors at all times. 
Separate written, signed informed consent must be obtained if the patient is to participate in the 
optional pharmacogenomic assessment. 

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15. 
DATA HANDLING AND RECORDKEEPING 
15.1. 
Maintaining Privacy and Confidentiality 
In order to maintain patient privacy, all CRFs, study drug accountability records, and other 
documents, including communications between the study site and Tonix, will identify patients 
only by their initials or their assigned study identification numbers.  If required, the investigator 
will grant monitors and auditors from Tonix or its designee and/or regulatory authority’s access 
to patients’ original medical records for verification of the data gathered on the CRFs and to 
audit the data collection process.  Patients’ confidentiality will be maintained and will not be 
made publicly available. 
Special Provisions for Confidentiality:  A Certificate of Confidentiality (CoC) has been 
obtained from the FDA for the investigators to protect patients enrolled in the study.  
Investigators may use the Certificate to avoid being compelled to make "involuntary disclosure" 
(e.g., subpoenas, insurers, employers, or other third parties) of names and other identifying 
information about any individual who participates as a research patient (i.e., about whom the 
investigator maintains identifying information) during any time the Certificate is in effect. 
15.2. 
Maintaining Essential Clinical Documents 
Study site files for the retention of regulatory documents will be established at the beginning of 
the study, maintained for the duration of the study, and retained according to FDA and ICH/GCP 
guidelines and applicable regulatory requirements.  The records maintained must be adequate to 
fully document appropriate protection of study patients/patients, the validity of the study, the 
integrity of the data, and the manner in which the study was conducted. 
The investigator’s site file, copies of protocols, CRFs, originals of test result reports, drug 
disposition logs, correspondence, records of written informed consent, and other documents 
pertaining to the conduct of the study must be kept on file by the investigator and in readily 
accessible order for at least 2 years after the last approval of a marketing application, until at 
least 2 years have elapsed after formal discontinuation of the clinical development of the 
investigational product, or according to local regulatory requirements.  No study document may 
be destroyed without prior written consent from Tonix or its designee.  Should the investigator 
wish to withdraw from the responsibility of keeping the study records, custody must be 
transferred to a person willing to accept the responsibility.  Tonix must be notified in writing in 
advance if a custodial change is to occur.  It is important that the investigator remain ready to 
provide background information from the archived study records on request. 
The sponsor or designee will maintain adequate study records for at least 2 years after the last 
approval of a marketing application or for at least 2 years after clinical development of the study 
drug for the indication being studied has been discontinued.  After that period, the sponsor will 
be contacted to determine whether the study records will be forwarded to the sponsor, destroyed, 
or kept at the location of the designee or another facility for a longer period of time. 

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15.3. 
Data Handling 
Unless otherwise specified, procedures, data collection and evaluation will be conducted as per 
the SOPs of the CRO.  The investigator will assume the responsibility of ensuring the 
completeness and accuracy of the clinical data.   
All laboratory results will be analyzed by an accredited and licensed clinical laboratory facility.  
Clinical laboratory data will be transferred from the central laboratory to the clinical database 
maintained by the CRO using systems which are validated and Part 11-compliant. 
The responsible clinical study monitor(s) will check data at the monitoring visits to the clinical 
study site.  The investigator will ensure that the data collected are accurate, complete, and 
legible.  Any changes made to the clinical data will be documented with a full audit trail. 
Aspects of the clinical and statistical phases of the study, including all associated documentation 
may be reviewed by the Quality Assurance Unit of the contract research organization using a 
risk-assessment approach.  The final clinical and statistical report will be audited to ensure that, 
as far as can be reasonably established, the methods described and the results reported accurately 
reflect the raw data generated during the study. 
15.4. 
Case Report Forms (CRFs) 
The investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other data pertinent to the study for each study patient.  
Data must be recorded on CRFs approved by Tonix or its designee.  Data (including AEs) will be 
recorded on raw data sheets and/or electronic or paper source documents. 
If selected data is collected via paper (patient questionnaires, etc.), the data must be entered into 
the eCRF and verified that it has been transcribed correctly. 
15.5. 
Screening Records 
A record must be kept of all patients considered for the study who sign informed consent and 
who began any screening procedures.  The information should include the patient’ initials, 
unique patient identification numbers, whether they passed or failed screening, and, if they 
failed, the reason for screen failure. 
15.6. 
Clinical Laboratory Certification 
A central clinical laboratory will be used to analyze all samples in this study, with the exception 
of the urine pregnancy test and ad hoc urine drug screens.  The investigator must maintain, on 
file, written evidence that the central clinical laboratory to be used is certified under the Clinical 
Laboratory Improvement Act or equivalent certification (depending on local regulations).  
Further, the investigator will maintain a copy of the certification, the range of normal values, the 
effective dates for the ranges, and the units of measurement for all laboratory tests requested in 
the protocol.  If any of the laboratory measurements will be transformed and/or categorized in 
any way, a description of the procedures(s) used should be included.  The investigator is 
expected to receive these documents before the shipment of clinical supplies. 

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15.7. 
Site Monitoring and Tonix’s Right to Review Records 
Monitoring and auditing procedures developed by Tonix and/or its designee will be implemented 
to ensure compliance with FDA and ICH GCP and GLP guidelines. 
Tonix’s designated representative (the monitor or auditor) will contact the investigator and 
conduct regular visits to the clinical site.  The monitor will be expected and allowed to verify the 
investigator’s qualifications, to inspect clinical site facilities, and to inspect study records, 
including proof of EC/IRB review, with the stipulation that patient confidentiality will be 
maintained in accordance with local and federal regulations, including HIPAA requirements.  
The monitor will also be responsible for confirming adherence to the study protocol, inspecting 
CRFs and source documents, and ensuring the integrity of the data.  CRFs will be checked for 
accuracy, completeness, and clarity and will be cross-checked for consistency with source 
documents, including laboratory test reports and other patient records.  Instances of missing or 
uninterpretable data will be resolved in coordination with the investigator. 
The monitor/auditor will also investigate any questions concerning adherence to regulatory 
requirements.  Any administrative concerns will be clarified and followed.  The monitor will 
maintain contact with the site through frequent direct communications with the study site by e-
mail, telephone, facsimile, and mail.  The investigator and all other site personnel agree to 
cooperate fully with the monitor and will work in good faith with the monitor to resolve any and 
all questions raised and difficulties detected by the monitor. 
15.8. 
Audits and Inspections 
The investigator understands that regulatory authorities, the EC/IRB, and/or Tonix or their 
designees have the right to access all CRFs, source documents, and other study documentation 
for on-site audit or inspection and will retain this right from the start of the study to at least 2 
years after the last approval of a marketing application or for at least 2 years after clinical 
development of the study drug for the indication being studied has been discontinued.  The 
investigator is required to guarantee access to these documents and to cooperate with and support 
such audits and inspections. 

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16. 
CONFIDENTIALITY 
16.1. 
Protection of Patient Anonymity 
The investigator must make sure that each patient’s anonymity is maintained.  On CRFs or other 
documents submitted to Tonix or its agent, patient should not be identified by their names, but 
rather by their initials and the assigned study identification numbers.  The investigator should 
keep a separate record of the patient initials, randomization codes, patient names, address, and 
contact information.  Documents that contain the names associated with these initials and codes 
are not for submission to Tonix or its agents (e.g., written informed consent forms).  These 
records should be maintained by the investigator in strict confidence except to the extent 
necessary to allow auditing by regulatory authorities, Tonix, or its agents.  These records should 
be kept in compliance with HIPAA regulations. 
Special Provisions for Confidentiality:  In addition, a Certificate of Confidentiality (CoC) has 
been obtained from the FDA for the investigators to protect patients enrolled in the study.  
Investigators can use the Certificate to avoid being compelled to make "involuntary disclosure" 
(e.g., subpoenas, insurers, employers, or other third parties) of names and other identifying 
information about any individual who participates as a research patient (i.e., about whom the 
investigator maintains identifying information) during any time the Certificate is in effect. 
16.2. 
Confidentiality of Study Information 
All information relevant to this study, whether supplied by Tonix or its agents to the investigator 
or collected by the investigator in support of this study, is privileged and confidential.  The 
investigator agrees to use this information to carry out the study and will not use it for other 
purposes without written consent from Tonix.  It is understood that the investigator is under 
obligation to provide Tonix with all data obtained during the study.  The information obtained 
from this study will be used by Tonix towards the clinical development of the indicated 
investigational drug and may be disclosed by Tonix to regulatory authorities, other investigators, 
corporate partners, or consultants as required. 
16.3. 
Publication of Data and Protection of Trade Secrets 
No presentations, abstracts (including meeting abstracts), or other publications based on the 
conduct or results of this study will be permitted without the express written permission of Tonix 
or its designated agent.  All such presentations or publications will proceed only as 
collaborations between Tonix and the investigators. 
If the investigator wishes to publish the results of this study, a copy of the proposed manuscript 
or abstract (including meeting abstracts) will be provided to Tonix or its designee for review, 
revision, and approval at least sixty (60) days before the expected date of submission for 
publication, unless otherwise arranged with Tonix in writing.  This will enable Tonix to protect 
its proprietary information and augment the publication with insights or information of which the 
investigator may not be aware. 
Patient names and other identifiers, such as photographs or audio or video recordings, may not 
be disclosed in any publication or public forum without prior written authorization from the 

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patients involved or their legal guardians.  Tonix retains authority to delete any of its confidential 
information from such disclosures. 

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17. 
LIST OF REFERENCES 
Stanley B and Brown GK.  Safety planning intervention: A brief intervention to mitigate suicide 
risk.  Cognitive and Behavioral Practice 2012; 19:256-264. 

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18. 
APPENDICES 
APPENDIX 1. STUDY DESIGN AND SCHEDULE OF ASSESSMENTS 
Period 
Baseline 
Phonef 
Clinic Visits 
Visit 
1 
2 
3 
4 
5 
6 
7j 
Study Week 
0 
2 
7 
16 
28 
40 
52 
Study Day 
0 
14 ± 3 
49 ± 7 
112 ± 7 
196 ± 7 
280 ± 7 
365 ± 7 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion Criteria  
X 
 
 
 
 
 
 
Concomitant Medicationsb 
X 
Xf 
X 
X 
X 
X 
X 
Vital Signs and weight  
Xa 
 
X 
X 
X 
X 
X 
Inspection of oral cavityc 
Xa 
 
 
 
X 
X i 
X 
Pregnancy Testd 
Xa 
 
X 
X 
X 
X 
X 
Clinical Laboratory Assessments 
Xa 
 
 
 
X 
X i 
X 
BDI-II 
Xa 
 
X 
X 
X 
X 
X 
C-SSRS 
Xa 
Xf 
X 
X 
X 
X 
X 
CGI-I (compared to P306 baseline only)e 
 
 
X 
X 
X 
X 
X 
PROMIS-Sleep (short form) 
Xa 
 
X 
X 
X 
X 
X 
SDS 
Xa 
 
X 
X 
X 
X 
X 
PCL-S 
 
 
 
 
Xh 
Xh 
X 
Pharmacogenomic blood draw 
(optional)g 
* 
* 
* 
* 
* 
* 
* 
Adverse Events 
X 
Xf 
X 
X 
X 
X 
X 
Telephone Visit 
 
Xf 
 
 
 
 
 
Dispense Study Drug 
X 
 
X 
X 
X 
Xj 
 
Collect/ Count Study Drug Returned 
 
 
X 
X 
X 
X 
X 
 
Abbreviations:  BDI-II = Beck Depression Inventory-II; C-SSRS = Columbia-Suicide Severity Rating Scales; CGI-I 
(Clinician Global Impression of Improvement); PROMIS = Patient Reported Outcomes Measurement Information 
System; SDS = Sheehan Disability Scale; PCL-S = PTSD Checklist-Specific Version  
 
a These assessments are only to be conducted for patients entering the study from Track B, or Track A patients that 
roll over into P306 greater than 14 days after the final visit of the previous study. 
b Medications that are ongoing at the end of the previous study will be recorded as such in this study. 
c In addition to the regularly scheduled examination, a visual examination of the oral cavity should be done at any 
visit in which an oral adverse event has been reported. 
d Women of child-bearing potential only. 
e The CGI-I will be done only in comparison to the baseline visit of P306.   
f Patients enrolled from the double-blind lead-in study, P301/HONOR, only will have the phone check-in. 

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*/gThe blood draw for the pharmacogenomic assessment can be obtained at any study visit (including an early 
termination visit).  It should only be obtained one time during the study.  Separate written, signed informed consent 
will be required if the patient is to participate in the optional pharmacogenomic assessment.  
h Visit 5(Week 28) will be the “baseline” for PCL-S because it will capture the vast majority of the patients who 
have enrolled from the start of P306. The mean change in PCL-S total score and PCL-S clusters scores from Visit 5 
(Week 28) to Visit 6 (Week 40), and to Visit 7 for Track B patients, will detect any potential worsening in total 
PTSD score or symptoms clusters due to long-term treatment of TNX-102 SL in the final 12-weeks, and 24-weeks 
for Track B patients, of the study.  
i Track A patients only. 
j Track B patients only. 
 
 

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APPENDIX 2. LIST OF CYP3A INHIBITORS 
Taken from Table 3, FDA Draft Guidance for Industry:  Drug Interaction Studies—Study 
Design, Data Analysis, Implications for Dosing, and Labeling Recommendations; Feb 2012; 
updated Sept. 26, 2016).  Excluded strong CYP3A4 inhibitors are listed in the far left column of 
the table. 
 
Strong Inhibitors 
 
≥ 5-fold increase in AUC  
Or, > 80% decrease in CL 
Moderate Inhibitors  
 
≥ 2 but < 5-fold increase in AUC  
Or 50-80% decrease in CL 
Weak Inhibitors 
 
≥ 1.25 but < 2-fold increase 
in AUC  
Or, 20-50% decrease in CL 
CYP3A4 
Boceprevir 
clarithromycin  
cobicistat 
conivaptan 
danoprevir 
elvitegravir 
grapefruit juice  
indinavir  
itraconazole 
ketoconazole  
lopinavir   
mibefradil 
nefazodone 
nelfinavir 
paritaprevir 
posaconazole 
ritonavir  
saquinavir  
telaprevir 
telithromycin 
tipranavir 
troleandomycin 
voriconazole 
 
amprenavir 
aprepitant 
atazanavir 
cimetidine 
ciprofloxacin 
clotrimazole 
crizotinib 
cyclosporine 
darunavir/ritonavir 
diltiazem 
dronedarone 
erythromycin 
fluconazole 
fluvoxamine 
fosamprenavir 
imatinib 
tofisopam 
verapamil 
alprazolam 
amiodarone 
amlodipine 
atorvastatin 
bicalutamide 
chlorzoxazone 
cilostazol 
fosaprepitant 
fluoxetine 
gingko 
goldenseal  
isoniazid 
istradefylline 
ivacaftor 
lapatinib 
lomitapide 
nilotinib 
oral contraceptives 
pazopanib 
ranitidine 
ranolazine 
tacrolimus 
tipranavir/ritonavir 
ticagrelor 
zileuton 
Source:  Table 3-2,  
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm 

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APPENDIX 3. AMRIX® PACKAGE INSERT (DATED MAY 2018) 
 

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