Clinical trial NCT05178316
Conditions: Post Traumatic Stress Disorder
Keywords: Post Traumatic Stress Disorder JZP150
Sponsor: Jazz Pharmaceuticals
Start date: 2021-12-29; Completion date: 2023-12-05
Enrollment: 282 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter study of the safety and efficacy of JZP150 in the treatment of adult participants with post-traumatic stress disorder (PTSD).

Detailed description:
JZP150 is an oral, highly selective inhibitor of fatty acid amide hydrolase (FAAH). In this phase 2 study, participants with PTSD will receive either placebo or 1 of 2 doses of JZP150. The primary objective of the study will assess the change in PTSD symptoms from baseline to Week 12 using the Clinician Administered PTSD Scale (CAPS-5).

Arms: arm 1: Participants who will be randomized to receive JZP150 0.3 mg orally once daily for up to 12 weeks. arm 2: Participants who will be randomized to receive JZP150 4.0 mg orally once daily for up to 12 weeks. arm 3: Participants who will be randomized to receive placebo orally once daily for up to 12 weeks.
Interventions: intervention 1: JZP150 intervention 2: Placebo
Intervention descriptions: intervention 1: Oral administration of JZP150 once daily in the morning intervention 2: Oral administration of placebo once daily in the morning

Protocol documents:
Prot_000.pdf: 
Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
1 
<date added by RegOps when sent to DocuSign> 
TITLE PAGE 
Protocol Title: A Multicenter Phase 2, 12-week Double-blind, Placebo-controlled, Randomized, 
Parallel-group, Study of JZP150 for the Treatment of Posttraumatic Stress Disorder 
Study Number: JZP150-201 
Protocol Number: JZP150-201-02 
Amendment Number: 02 
Compound: JZP150 
Brief Title: A Study of JZP150 in Adults with Posttraumatic Stress Disorder 
Study Phase: Phase 2 
Sponsor Name: Jazz Pharmaceuticals, Inc. 
Legal Registered Address: 3170 Porter Drive, Palo Alto, CA, USA 94304 
Regulatory Agency Identifier Number(s): IND: 
 
CONFIDENTIAL
Page 1 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
2 
<date added by RegOps when sent to DocuSign> 
Sponsor Signatory: 
        {Please see appended electronic signature page} 
 MD 
Senior Director, Clinical Development 
Date 
Investigator Signatory: 
[Name] 
[Title] 
Date 
Medical monitor name and contact information can be found in the Investigator Trial Site 
Binder (or equivalent).  
CONFIDENTIAL
Page 2 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
3 
<date added by RegOps when sent to DocuSign> 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2 
Amendment 1 
14 October 2021 
Original Protocol 
30 July 2021 
Amendment 2 
Overall Rationale for the Amendment: 
This amendment is being implemented primarily to broaden the eligible participant population 
consistent with literature, and thereby allowing the study population to be more generalizable to 
the PTSD patient population. The sponsor has also taken the opportunity to include clarity and 
guidance for study procedures and assessments. There are no major changes to overall study 
design, primary or key secondary efficacy endpoints, dosing, or the participant population. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis,  
4.1 Overall Design, and 
4.2 Scientific Rationale for 
Study Design / PTSD 
diagnosis and severity of 
condition 
PCL score requirement was 
lowered from ≥ 35 to ≥ 33. 
A cut-score of ≥ 35 was 
originally implemented to be 
conservative end of a baseline 
score. However, the literature 
has demonstrated that scores 
between 31 and 33 on the PCL-5 
are optimally efficient for 
diagnosing PTSD (Bovin, 2016). 
Thus, the minimum PCL-5 score 
has been reduced to ≥ 33 for 
consistency with the literature, 
recommendations of cut-scores 
by the National Center for 
PTSD, and to have a range of 
scores that is generalizable to the 
patient population. 
CONFIDENTIAL
Page 3 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
4 
<date added by RegOps when sent to DocuSign> 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis and  
3 Objectives and 
Estimands/Assessments 
Revisions to the timing of 
the analyses of some 
secondary endpoints: 
• PCL-5 and PGI-S / CGI-
S were separated into
2 endpoints.
• PGI-S and CGI-S:
Change from Baseline to
Week 12 removed.
• This endpoint was separated
into 2 as the change in patient
and clinician-reported
symptoms of PGI-S and
CGI-S from Baseline to
Week 12 is already captured as
a key secondary endpoint.
• The secondary endpoint
for PTSD symptoms
clusters were revised as:
−‘Re-experiencing’ has
been changed to
‘Intrusive symptoms,’
−‘Avoidance’ has been
changed to ‘Avoidance
symptoms,’
−‘Arousal’ has been
changed to
‘Arousal/reactivity
symptoms,’
−‘Mood’ has been
changed to ‘Negative
alterations in mood and
cognition.’
• PTSD symptom clusters:
Change from Baseline to
Week 4 was added.
• PTSD symptom clusters were
revised to reflect what is in
DSM-5, and to include
assessment of change from
Baseline to Week 4.
CONFIDENTIAL
Page 4 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
5 
<date added by RegOps when sent to DocuSign> 
Section # and Name 
Description of Change 
Brief Rationale 
• Mood and anxiety
(PHQ-9): Change from
Baseline to Week 1 added
and Week 8 removed.
• PHQ-9 is assessed at Baseline
and Weeks 1, 4, and 12.
1.3 Schedule of Activities 
Minor procedural 
clarifications, consistent 
with the protocol body, 
were included.   
To provide better guidance with 
the SoA. 
Dispensation and training 
on the digital tool and 
medication adherence 
application will be 
performed at Visit 2 post 
randomization (not Visit 1). 
To ensure eligibility prior to 
additional training and 
equipment dispensation. 
2.2 Background and  
2.3 Benefit/Risk 
Assessment 
Correction to the anticipated 
human exposure compared 
to the NOAELs from the 
13-week studies in rats and
dogs.
Alignment with the recently 
updated JZP150 Investigator’s 
Brochure. 
5.1 Inclusion Criteria 
PCL score requirement was 
lowered from ≥ 35 to ≥ 33. 
As noted above, the minimum 
PCL-5 score has been reduced to 
≥ 33 for consistency with the 
literature, recommendations of 
cut-scores by the National Center 
for PTSD, and to have a range of 
scores that is generalizable to the 
patient population. 
Maximum BMI increased 
from 35 to 40 kg/m2. 
The increase in BMI should 
broaden the eligible participant 
population, as literature indicates 
an association between PTSD 
and higher BMI (Suliman, 2016). 
Eligibility criteria already in the 
CONFIDENTIAL
Page 5 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
6 
<date added by RegOps when sent to DocuSign> 
Section # and Name 
Description of Change 
Brief Rationale 
protocol will minimize risk 
associated with obesity.   
5.2 Exclusion Criteria 
#24. Examples of 
prescription drugs was 
removed. 
The examples given led to 
confusion; participants receiving 
barbiturates, benzodiazepines 
should be excluded for safety 
reasons.   
6.8 Concomitant Therapy 
Added a sentence, “For 
details on prohibited and 
cautionary medications 
please refer to the 
Prohibited and Cautionary 
Medication document that 
has been provided.” 
Additional guidance. 
7 Discontinuation of Study 
Intervention and Participant 
Discontinuation/Withdrawal 
“End of Study Visit” 
revised to “Early 
Discontinuation Visit, 
Efficacy Follow-up Visit (if 
applicable), and Safety 
Follow-up Visit.” 
Consistency with the SoA/Study 
Visits. 
8.2.5 Brief Inventory of 
Psychosocial Functioning 
Correction from 6- to 7-
point scale. 
Correction of a typographical 
error. 
8.3.2 Vital Signs 
Added guidance regarding 
repeating blood pressure 
measurements. 
For clarification. 
8.4.6 Adverse Events of 
Special Interest 
Clarification regarding the 
intention for monitoring and 
reporting of AEOSIs. 
Alignment with Protocol 
Clarification Letter, dated 
17 November, 2021. 
8.5 Pharmacokinetics 
Revisions for internal 
consistency with text and 
intended procedures. 
Clarification/consistency with 
the Laboratory Manual. 
9.3 Analysis Sets 
Revisions to the definitions 
of the FAS, mFAS 
(previously mITT), PK 
Analysis Sets and addition 
of a PD Analysis Set. 
Revision to analyses to be 
performed using the 
Enrolled Analysis Set. 
Alignment with the recently-
drafted Statistical Analysis Plan. 
CONFIDENTIAL
Page 6 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
7 
<date added by RegOps when sent to DocuSign> 
Section # and Name 
Description of Change 
Brief Rationale 
9.4.2 Primary Estimand 
Inclusion of “baseline-by-
week” and “stratum-by-
week” interactions in the 
MMRM to be used for 
efficacy analyses. 
Alignment with the recently-
drafted Statistical Analysis Plan 
to allow for a more appropriate 
model fit by accounting for 
different coefficients of 
baseline/stratum at each 
postbaseline visit and thus avoid 
potential convergence issue due 
to insufficient model 
specification.  
Appendix 3 Clinical 
Laboratory Tests 
Added specifics regarding 
fasting prior to visits. 
Clarification regarding when 
participants needed to fast prior 
to study visits, aligned with the 
Protocol Clarification Letter, 
dated 15 August 2022. 
Appendix 4 Adverse Events 
and Serious Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, and Follow-up, 
and Reporting 
Deletion of reference to 
CTCAE, v5.0 for AE 
‘Assessment of Intensity.’ 
Addition of note that the 
intensity scale to be used is 
based on the CTCAE, v5 or 
higher. 
To alleviate confusion that 
CTCAE, v5.0 needed to be 
consulted for assessment of AE 
intensity.  
Minor revision to ensure 
review of Section 8.4.6 
prior to reporting an 
AEOSI. 
Clarification of reporting, in 
alignment with the revisions in 
Section 8.4.6. 
Appendix 7 Liver Safety: 
Suggested Actions and 
Follow-up Assessments 
Clarifications with respect 
to reporting liver 
abnormalities that may meet 
liver stopping or serious 
adverse event criteria.  
Clarification on reporting 
signs/symptoms, 
evaluations, and 
medications to facilitate a 
full understanding of 
reported liver abnormalities. 
Clarification regarding how liver 
abnormalities and follow-up 
assessments should be reported 
to the sponsor. 
CONFIDENTIAL
Page 7 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
8 
<date added by RegOps when sent to DocuSign> 
TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................3 
TABLE OF CONTENTS .................................................................................................................8 
LIST OF TABLES .........................................................................................................................13 
1. 
PROTOCOL SUMMARY ..........................................................................................14 
1.1. 
Synopsis ......................................................................................................................14 
1.2. 
Schema ........................................................................................................................19 
1.3. 
Schedule of Activities (SoA) ......................................................................................20 
2. 
INTRODUCTION ......................................................................................................28 
2.1. 
Study Rationale ...........................................................................................................28 
2.2. 
Background .................................................................................................................29 
2.3. 
Benefit/Risk Assessment ............................................................................................31 
2.3.1. 
Risk Assessment .........................................................................................................31 
2.3.2. 
Benefit Assessment .....................................................................................................31 
2.3.3. 
Overall Benefit: Risk Summary ..................................................................................32 
3. 
OBJECTIVES AND ESTIMANDS/ASSESSMENTS ..............................................33 
4. 
STUDY DESIGN .......................................................................................................37 
4.1. 
Overall Design ............................................................................................................37 
4.2. 
Scientific Rationale for Study Design ........................................................................37 
4.3. 
Justification for Dose ..................................................................................................39 
4.4. 
End of Study Definition ..............................................................................................40 
5. 
STUDY POPULATION .............................................................................................41 
5.1. 
Inclusion Criteria ........................................................................................................41 
5.2. 
Exclusion Criteria .......................................................................................................43 
5.3. 
Lifestyle Considerations .............................................................................................46 
5.3.1. 
Meals and Dietary Restrictions ...................................................................................46 
5.3.2. 
Caffeine, Alcohol, and Tobacco .................................................................................46 
5.4. 
Screen Failures ............................................................................................................46 
5.5. 
Criteria for Temporarily Delaying Administration of Study Intervention 
Administration ............................................................................................................47 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY ........................48 
CONFIDENTIAL
Page 8 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
9 
<date added by RegOps when sent to DocuSign> 
6.1. 
Study Intervention(s)/Treatment(s) Administered ......................................................48 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................50 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................50 
6.4. 
Study Intervention/Treatment Compliance .................................................................51 
6.5. 
Dose Modification ......................................................................................................51 
6.6. 
Continued Access to Study Intervention After the End of the Study .........................51 
6.7. 
Treatment of Overdose, Medication Errors, or Misuse ..............................................51 
6.8. 
Concomitant Therapy .................................................................................................52 
6.8.1. 
Use of Concomitant SSRIs/SNRIs .............................................................................52 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......................................54 
7.1. 
Discontinuation of Study Intervention ........................................................................54 
7.1.1. 
Liver Chemistry Stopping Criteria .............................................................................55 
7.1.2. 
QTc Stopping Criteria .................................................................................................55 
7.1.3. 
 .................................................................55 
7.1.4. 
Temporary Discontinuation/Study Intervention Interruption .....................................55 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...........................................55 
7.3. 
Lost to Follow-up .......................................................................................................56 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................57 
8.1. 
General Administrative Procedures ............................................................................58 
8.1.1. 
Informed Consent .......................................................................................................58 
8.1.2. 
Assignment of Participant Number ............................................................................58 
8.1.3. 
Medical History ..........................................................................................................58 
8.1.4. 
Medication Review (Prior and Concomitant Medications) ........................................58 
8.1.5. 
Inclusion and Exclusion Criteria Review ...................................................................58 
8.1.6. 
Timing of Study Intervention Dosing .........................................................................59 
8.1.7. 
Mini International Neuropsychiatric Interview (MINI) .............................................59 
8.1.8. 
Life Events Checklist (LEC) ......................................................................................59 
8.2. 
Efficacy Assessments .................................................................................................59 
8.2.1. 
Clinician Administered PTSD Scale (CAPS-5) .........................................................59 
8.2.2. 
Clinical Global Impression of Severity (CGI-S) ........................................................59 
8.2.3. 
Clinical Global Impression of Change (CGI-C) .........................................................60 
8.2.4. 
Patient Global Impression of Severity (PGI-S) ..........................................................60 
CONFIDENTIAL
Page 9 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
10 
<date added by RegOps when sent to DocuSign> 
8.2.5. 
Brief Inventory of Psychosocial Functioning (B-IPF) ................................................60 
8.2.6. 
Sheehan Disability Scale (SDS) .................................................................................60 
8.2.7. 
PTSD Checklist (PCL-5) ............................................................................................60 
8.2.8. 
Insomnia Severity Index (ISI) ....................................................................................60 
8.2.9. 
Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI-A) .............................61 
8.2.10. 
Patient Health Questionnaire (PHQ-9) .......................................................................61 
8.2.11. 
Structured Interview Guide for the Hamilton Anxiety Rating Scale 
(SIGH-A) ....................................................................................................................61 
8.2.12. 
Recovering Quality of Life (ReQoL) .........................................................................61 
8.3. 
Safety Assessments .....................................................................................................61 
8.3.1. 
Physical Examinations ................................................................................................61 
8.3.2. 
Vital Signs ..................................................................................................................62 
8.3.3. 
Electrocardiograms .....................................................................................................62 
8.3.4. 
Clinical Safety Laboratory Assessments ....................................................................62 
8.3.5. 
Pregnancy Testing ......................................................................................................63 
8.3.6. 
Suicidal Ideation and Behavior Risk Monitoring .......................................................63 
8.3.7. 
Marijuana Withdrawal Checklist ................................................................................64 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other Safety 
Reporting ....................................................................................................................64 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................64 
8.4.2. 
Method of Detecting AEs and SAEs ..........................................................................64 
8.4.3. 
Follow-up of AEs and SAEs .......................................................................................65 
8.4.4. 
Regulatory Reporting Requirements for SAEs ...........................................................65 
8.4.5. 
Pregnancy ...................................................................................................................65 
8.4.6. 
Adverse Events of Special Interest .............................................................................66 
8.4.7. 
Overdose, Medication Errors, and Misuse .................................................................66 
8.5. 
Pharmacokinetics ........................................................................................................67 
8.6. 
Pharmacogenomics .....................................................................................................67 
8.7. 
Biomarkers ..................................................................................................................67 
8.8. 
Immunogenicity Assessments ....................................................................................68 
8.9. 
Medical Resource Utilization and Health Economics ................................................68 
9. 
STATISTICAL CONSIDERATIONS .......................................................................69 
9.1. 
Statistical Hypotheses .................................................................................................69 
CONFIDENTIAL
Page 10 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
11 
<date added by RegOps when sent to DocuSign> 
9.2. 
Sample Size Determination ........................................................................................69 
9.3. 
Analysis Sets ...............................................................................................................69 
9.4. 
Statistical Analyses .....................................................................................................70 
9.4.1. 
General Considerations ...............................................................................................70 
9.4.1.1. 
Multiplicity Adjustments ............................................................................................70 
9.4.1.2. 
Intercurrent Event Strategies ......................................................................................71 
9.4.1.3. 
Pooling of Investigational Centers ..............................................................................71 
9.4.1.4. 
Dropouts and Missing Data ........................................................................................71 
9.4.2. 
Primary Estimand .......................................................................................................72 
9.4.3. 
Key Secondary Estimands ..........................................................................................72 
9.4.4. 
Secondary and Exploratory Estimands .......................................................................72 
9.4.5. 
Safety Analyses ..........................................................................................................73 
9.4.6. 
Other Analyses ............................................................................................................73 
9.4.7. 
Pharmacokinetic/ Pharmacodynamic Analyses ..........................................................74 
9.5. 
Interim Analysis ..........................................................................................................74 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................75 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations .........................................75 
10.1.1. 
Regulatory and Ethical Considerations ......................................................................75 
10.1.2. 
Financial Disclosure ...................................................................................................75 
10.1.3. 
Informed Consent Process ..........................................................................................76 
10.1.4. 
Data Protection ...........................................................................................................76 
10.1.5. 
Committees Structure .................................................................................................77 
10.1.6. 
Dissemination of Clinical Study Data ........................................................................78 
10.1.7. 
Data Quality Assurance ..............................................................................................78 
10.1.8. 
Source Documents ......................................................................................................79 
10.1.9. 
Study and Site Start and Closure ................................................................................79 
10.1.9.1. 
First Act of Recruitment .............................................................................................79 
10.1.9.2. 
Study/Site Termination ...............................................................................................79 
10.1.10. 
Publication Policy .......................................................................................................80 
APPENDIX 1. ABBREVIATIONS ............................................................................................81 
APPENDIX 2. REFERENCES ...................................................................................................84 
APPENDIX 3. CLINICAL LABORATORY TESTS ................................................................88 
CONFIDENTIAL
Page 11 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
12 
<date added by RegOps when sent to DocuSign> 
APPENDIX 4. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING ...............................................91 
APPENDIX 5. CONTRACEPTIVE AND BARRIER GUIDANCE .........................................97 
APPENDIX 6. GENETICS .........................................................................................................99 
APPENDIX 7. LIVER SAFETY: SUGGESTED ACTIONS AND FOLLOW-UP 
ASSESSMENTS .......................................................................................................100 
 
 
CONFIDENTIAL
Page 12 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
13 
<date added by RegOps when sent to DocuSign> 
LIST OF TABLES 
Table 1:  
Objectives and Estimands/Assessments .....................................................................14 
Table 2: 
Overall Study Design ..................................................................................................18 
Table 3: 
Schedule of Assessments ............................................................................................20 
Table 4: 
Study Treatment/Intervention .....................................................................................49 
Table 5: 
Hierarchical Testing Strategy .....................................................................................71 
Table 6: 
Protocol-Required Safety Laboratory Tests ...............................................................88 
Table 7: 
Phase 2 Liver Chemistry Stopping Criteria and Follow-up Assessments ................100 
Table 8: 
Phase 2 Liver Chemistry Increased Monitoring Criteria with Continued 
Study Intervention ....................................................................................................102 
 
 
 
CONFIDENTIAL
Page 13 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
14 
<date added by RegOps when sent to DocuSign> 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title:  
A Multicenter Phase 2, 12-week Double-blind, Placebo-controlled, Randomized, Parallel-group, 
Study of JZP150 for the Treatment of Posttraumatic Stress Disorder 
Brief Title: A Study of JZP150 in Adults with Posttraumatic Stress Disorder  
Rationale: 
This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group study of the 
safety and efficacy of JZP150 in the treatment of adult participants with posttraumatic stress 
disorder (PTSD). JZP150 (previously known as PF-04457845) is an orally available, highly 
selective and irreversible inhibitor of fatty acid amide hydrolase (FAAH). 
The purpose of this phase 2 study is to provide an evaluation of the efficacy and safety of 
JZP150 in participants with PTSD, while evaluating a broad range of JZP150 doses to support 
pharmacokinetic (PK)/pharmacodynamics (PD) exposure-response analysis. Results from this 
study will be used to inform the study design, patient population, and dose selection for future 
studies in PTSD. 
Multiple preclinical and clinical studies have demonstrated the association between the 
endocannabinoid system and the underlying pathophysiology of PTSD, which JZP150 directly 
targets (ie, augmentation of anandamide [AEA] levels).  
A double-blind, placebo-controlled experimental study examined the effect of JZP150 on 
experimentally induced fear conditioning and extinction, and stress response among healthy 
volunteers. Study participants on 4 mg JZP150 once daily (QD) compared to placebo had 
improved recall of fear extinction 24 hours later and did not have the typical reduction in AEA in 
response to acute stress. Furthermore, those participants who were randomized to JZP150 had 
decreased stress-induced reactivity to emotional pictures demonstrating an attenuation of 
negative affect. 
Results from previous studies in animals and humans suggest that FAAH inhibition with JZP150 
may positively influence many of the core symptoms experienced by patients with PTSD. 
Objectives and Estimands/Assessments:  
Table 1:  
Objectives and Estimands/Assessments 
 
Objectives 
Estimands/Assessments 
Primary 
 
To evaluate the efficacy of JZP150 administered 
once daily for up to 12 weeks at doses of 0.3 mg 
and 4 mg compared to placebo in the treatment of 
adults with PTSD, as measured by the change in 
Clinician Administered PTSD Scale (CAPS-5) 
total symptom severity score. 
The primary estimand is defined as follows: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo. 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
CONFIDENTIAL
Page 14 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
15 
<date added by RegOps when sent to DocuSign> 
Objectives 
Estimands/Assessments 
• 
Variable (endpoint): CAPS-5 total symptom 
severity score change from Baseline to 
Week 12. 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in CAPS-5 
for each treatment group and the difference in 
means between each randomized treatment 
group compared to placebo. 
Key Secondary 
 
To evaluate the efficacy of JZP150 administered 
once daily for 12 weeks at doses of 0.3 mg and 
4 mg compared to placebo on overall clinician 
and patient global impression of severity. 
The two key secondary estimands are defined as 
follows: 
Key Secondary Estimand 1: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo. 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
• 
Variable (endpoint): Change in Clinical 
Global Impression of Severity (CGI-S) from 
Baseline to Week 12. 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in CGI-S 
for each treatment group and the difference in 
means between each randomized treatment 
group compared to placebo. 
Key Secondary Estimand 2: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
• 
Variable (endpoint): Change in Patient 
Global Impression of Severity (PGI-S) from 
Baseline to Week 12. 
CONFIDENTIAL
Page 15 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
16 
<date added by RegOps when sent to DocuSign> 
Objectives 
Estimands/Assessments 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in PGI-S 
for each treatment group and the difference in 
means between each randomized treatment 
group compared to placebo. 
Secondary  
 
To evaluate the efficacy of JZP150 administered 
once daily for 12 weeks at doses of 0.3 mg and 
4 mg compared to Placebo on functional 
outcomes and patient reported symptoms in adults 
with PTSD 
All other secondary and exploratory estimands are 
defined using the same estimand attributes 
(treatment, population, ICEs, and population-level 
summary, difference in means or proportions 
between each randomized treatment and placebo, 
as appropriate) as described above. The variables 
(endpoints) for the estimands are: 
• 
Responder analysis defined in 3 separate 
ways: 
o 
Percent of participants with ≥ 30% 
improvement on the CAPS-5 total 
symptom severity score from Baseline to 
Week 12 
o 
Percent of participants who are very much 
or much improved on the CGI-C at 
Weeks 4 and 12 
o 
Percent of participants with ≥ 1 unit of 
improvement on the PGI-S from Baseline 
to Week 12 
• 
CAPS-5 total symptom severity score change 
from Baseline to Week 4. 
• 
Change in functional outcomes measured by 
the Brief Inventory of Psychosocial 
Functioning (B-IPF) and Sheehan Disability 
Scale (SDS) from Baseline to Week 12.  
• 
Change in patient-reported symptoms of 
PTSD as assessed by the PTSD Checklist 
(PCL-5) from Baseline to Week 1, 4, 8, and 
12.  
• 
Change in patient- and clinician-reported 
symptoms of PTSD as assessed by the PGI-S, 
CONFIDENTIAL
Page 16 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
17 
<date added by RegOps when sent to DocuSign> 
Objectives 
Estimands/Assessments 
and CGI-S from Baseline to Weeks 1, 4, and 
8. 
• 
Change in self-reported sleep problems as 
measured by the Insomnia Severity Index 
(ISI) and Pittsburgh Sleep Quality Index-
PTSD Addendum (PSQI-A) from Baseline to 
Week 12. 
• 
Change in PTSD symptom clusters (intrusive 
symptoms, avoidance symptoms, 
arousal/reactivity symptoms, negative 
alterations in mood and cognition) as assessed 
by the change in the sub-scales of the CAPS-5 
from Baseline to Week 4 and Week 12. 
• 
Change in mood and anxiety from Baseline to 
Weeks 1, 4, and 12 as assessed by the Patient 
Health Questionnaire (PHQ-9) and change 
from Baseline to Weeks 4, 8, 12 on the 
Structured Interview Guide for the Hamilton 
Anxiety Scale (SIGH-A). 
• 
Change in quality of life from Baseline to 
Week 12 as measured by the Recovering 
Quality of Life (ReQoL). 
To evaluate the safety and tolerability of JZP150 
administered once daily for up to 12 weeks at 
doses of 0.3 mg and 4 mg in adults with PTSD. 
The safety of JZP150 will be evaluated by the 
following assessments:  
• 
Adverse events (AEs) 
• 
Vitals signs 
• 
Physical examinations 
 
• 
12-lead ECG 
• 
Clinical laboratory tests (chemistry, 
hematology, urinalysis
 
 
• 
C-SSRS 
• 
Withdrawal scale (marijuana withdrawal 
checklist) 
To characterize the PK and PD of JZP150 in 
adults with PTSD using population PK modeling 
and simulation methodology. 
Plasma concentration of AEA, JZP150 and its 
metabolites 
CONFIDENTIAL
Page 17 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
18 
<date added by RegOps when sent to DocuSign> 
Objectives 
Estimands/Assessments 
 
 
 
 
 
 
 
 
 
 
 
Brief Summary: 
This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter 
study of the safety and efficacy of JZP150 in the treatment of adult participants with PTSD. 
Participants who meet DSM-5 criteria for PTSD as confirmed by the Mini International 
Neuropsychiatric Interview (MINI), with a total PCL-5 score ≥ 33 at Screening and Baseline will 
be eligible for enrollment. 
Approximately 270 participants will be randomized (2:1:2) to receive placebo, 0.3 mg JZP150, 
or 4 mg JZP150 to ensure that a minimum of 188 participants have 12 weeks of treatment data. 
Participants will be stratified by the presence or absence of concomitant use of selective 
serotonin reuptake inhibitor (SSRIs)/ serotonin norepinephrine reuptake inhibitor (SNRIs).  
Overall Design: 
Table 2: 
Overall Study Design 
Overall Design 
Study Phase 
2 
Clinical Indication 
PTSD 
Study Type 
Interventional 
Type of Design 
Randomized, parallel-group, multicenter. 
Participants will be stratified by the presence or 
absence of concomitant use of SSRIs/ SNRIs. 
Type of Control 
Placebo control 
Study Blinding 
Double-blind 
Population 
Participants who meet DSM-5 criteria for PTSD 
as confirmed by the MINI, with a total PCL-5 
score ≥ 33 at Screening and Baseline to be eligible 
for enrollment.  
Number of Participants  
To account for a 30% dropout, approximately 
270 participants will be randomized (2:1:2) to 
receive placebo, 0.3 mg JZP150, or 4 mg JZP150 
CONFIDENTIAL
Page 18 of 102


Jazz Pharmaceuticals Inc. 
JZP150 
Protocol JZP150-201-02 
 Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
19 
<date added by RegOps when sent to DocuSign> 
Overall Design 
to ensure that a minimum of 188 participants have 
12 weeks of treatment data (Section 9). 
Duration of Participation 
Each subject will participate in the study from 
the time they sign the informed consent form 
(ICF) through the end of the study 
procedures/contact. The study comprises 3 
phases: up to 28 days screening period 
followed by a 12-week double-blind treatment 
period and a 2-week safety follow-up. Each 
participant will be enrolled for approximately 
18 weeks.  
Number of Treatment Arms 
3 
Treatment Groups 
Placebo, JZP150 (0.3 mg), JZP150 (4 mg) 
Data Monitoring Committee 
An independent data safety monitoring committee 
is not planned. An internal safety data review 
committee will review the accumulating safety 
data in a blinded manner. 
1.2. 
Schema 
QD = once daily. 
CONFIDENTIAL
Page 19 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
20 
1.3. 
Schedule of Activities (SoA) 
Table 3: 
Schedule of Assessments  
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Clinic Visits  
(end of week) 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
Week 8 clinic visit 
should be scheduled for 
the afternoon/evening; 
participants should dose 
at home in the morning 
on the day of the Week 8 
clinic visit 
Digital/Phone 
 
 
 
X 
 
X 
 
X 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Full physical 
examination 
including height, 
weight
 
 
X 
X 
 
 
X 
 
X 
 
X 
X 
 
 
Height is collected at 
Screening only 
CONFIDENTIAL
Page 20 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
21 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Medical history 
(includes substance 
use and legal 
claims/disability 
related to PTSD) 
X 
 
 
 
 
 
 
 
 
 
 
 
Substances: illicit drugs, 
alcohol, nicotine, 
caffeine, and cannabis 
Past and current 
medical conditions   
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum OR urine 
pregnancy test 
(WOCBP only) 
X (S&U) 
X(U) 
 
 
 
 
 
 
X (U) 
X 
(U) 
 
X (U) 
S = Serum 
U = Urine 
Urine pregnancy is 
conducted at the site via 
dipstick. A serum 
pregnancy test is also 
done at the central 
laboratory at Screening. 
Laboratory 
assessmentsd 
(chemistry, 
hematology, 
urinalysi
 
 
  
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
X 
TSH is done at Screening 
only; HbA1c is done at 
Screening and Week 12. 
See Table 6 for details. 
Triplicate 12-lead 
ECG 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
 
CONFIDENTIAL
Page 21 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
22 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Urine drug screen  
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
Conducted by the central 
laboratory at Screening 
and at the site via dipstick 
at visits subsequent to 
Screening. 
Breath alcohol test 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
 
Vital signs 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
X 
Vitals can be repeated 
once at Screening and 
Baseline. See 
Section 8.3.2 for details. 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
Stratified based on 
presence/absence of 
concomitant use of 
SSRI/SNRI 
CAPS-5 
  
X 
 
 
X 
 
 
 
X 
X 
X 
 
 
MINI 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medication 
washout  
X 
 
 
 
 
 
 
 
 
 
 
 
Washout of prohibited 
medications if needed. 
Please refer to the 
Prohibited and 
Cautionary Medication 
Document for additional 
information. 
CONFIDENTIAL
Page 22 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
23 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
C-SSRS 
Baseline/Screening 
version 
X 
 
 
 
 
 
 
 
 
 
 
 
 
C-SSRS Since last 
visit version 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CGI-S 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
CGI-C 
 
 
 
 
X 
 
 
 
X 
X 
X 
X 
 
PGI-S 
 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
PCL-5  
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
LEC 
X 
 
 
 
 
 
 
 
 
 
 
 
 
B-IPF 
 
X 
 
 
 
 
 
 
X 
X 
 
 
 
ReQoL-10 
 
X 
 
 
 
 
 
 
X 
 
 
 
 
SDS 
 
X 
 
 
X 
 
 
 
X 
X 
 
 
 
PSQI-A 
 
X 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
ISI 
 
X 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
PHQ-9  
X 
X 
X 
 
X 
 
 
 
X 
X 
 
X 
 
SIGH-A 
 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
CONFIDENTIAL
Page 23 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
24 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Withdrawal scale 
(Marijuana 
withdrawal 
checklist) 
 
X 
 
 
 
 
 
 
X 
X 
 
X 
 
Pharmacogenomics  
 
X 
 
 
 
 
 
 
 
 
 
 
 
Samples that are not 
collected at Baseline may 
be drawn at any 
subsequent visit. 
Blood draws for 
PK  
 
 
X 
 
 
 
X 
 
X 
 
 
 
Week 12 PK sample 
post-dose should be 
collected after the 
collection of the CAPS-5 
assessment. Refer to 
Section 8.5 for details. 
Blood draws for 
AEA levels 
 
X 
X 
 
 
 
X 
 
X 
 
 
X 
Refer to Section 8.7 for 
details. 
Administration of 
study intervention 
in clinicc 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
Administration of 
study intervention 
at home 
 
 
 
X 
 
X 
X 
X 
 
 
 
 
 
CONFIDENTIAL
Page 24 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
25 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Provide light meal 
or snack 
X 
X 
X 
 
X 
 
 
 
X 
X 
 
 
 
Dispense study 
intervention 
 
Xc 
X 
 
X 
 
X 
 
 
 
 
 
 
Collect study 
intervention/assess 
compliance 
 
 
X 
 
X 
 
X 
 
X 
X 
 
 
 
Dispense and train 
on digital tool and 
medication 
adherence 
application 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Read expectancies 
script (placebo 
mitigation) 
X 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
 
Medication 
adherence 
application 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Intent to attend 
assessment 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Schedule/confirm 
next visit and or 
phone call 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
CONFIDENTIAL
Page 25 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
26 
Procedure 
Screening  
(up to 28 
days) 
Intervention Period (Weeks) 
E/Da 
Efficacy 
Follow-upb 
(Only 
conducted 
for 
participants 
that 
discontinue 
study 
intervention) 
Safety 
Follow-
up 
(14 
days 
after 
last 
dose) 
Notes 
Baseline/ 
Randomization 
-1c  
1 
2 
4 
6 
8 
10 
12 
 
 
Visit Number 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
 
Visit Window 
(days) 
 
 
±2 
±2 
±2 
±2 
±2 
±2 
-5/+2 
 
 
+5 
 
Phone call check-in 
 
 
 
X 
 
X 
 
X 
 
 
 
 
 
AE review 
 
X 
============================= 
X 
 
X 
For medical occurrences 
that begin before the start 
of study intervention, but 
after obtaining informed 
consent, details are 
provided in Section 8.4.1. 
SAE reviewe 
 
X 
============================= 
 
X 
 
X 
 
Prior and 
concomitant 
medication review 
X 
X 
============================= 
X 
X 
X 
Screening visit: assess 
prior and concomitant 
medications; all 
subsequent visits include 
concomitant medication 
review only 
Abbreviations. AE = adverse event; AEA = anandamide; B-IPF = Brief Inventory of Psychosocial Functioning; E/D = Early Discontinuation; CAPS-5 = 
Clinician Administered PTSD Scale version 5; CGI-C = Clinical Global Impression of Change; CGI-S = Clinical Global Impression of Severity; C-SSRS = 
Columbia Suicide Severity Rating Scale; ECG = electrocardiogram; E/D = Early Discontinuation; 
 HbA1c = glycosylated 
hemoglobin; ISI = Insomnia Severity Index; LEC = Life Events Checklist; 
 MINI = Mini International Neuropsychiatric Interview; 
PCL-5 = Posttraumatic Checklist-5; PGI-S = Patient Global Impression of Severity; PHQ-9 =Patient Heath Questionnaire-9; PK = pharmacokinetics; PSQI-A = 
Pittsburgh Sleep Quality Index with PTSD Addendum; PTSD = posttraumatic stress disorder; ReQoL = Recovering Quality of Life; SAE = serious adverse 
event; SDS = Sheehan Disability Scale; SIGH-A = Structured Interview Guide for the Hamilton Anxiety Rating Scale; TSH = thyroid stimulating hormone; 
WOCBP= women of childbearing potential. 
a The E/D visit is conducted for participants who prematurely discontinue from the study intervention and the study. 
CONFIDENTIAL
Page 26 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
Protocol JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
27 
b The efficacy follow-up visit is conducted for participants who discontinue study intervention but remain in the study to complete scheduled assessments. For 
participants who discontinue study intervention early, every effort should be made to obtain an efficacy follow-up 12 weeks after first dose. An additional 
efficacy follow-up at 4 weeks is encouraged for participants who discontinue study intervention prior to Week 4. For those participants who discontinue study 
intervention but who otherwise continue in the study, the assessments included in these visits may be performed during the participants’ safety follow-up visit 
if that efficacy follow-up is scheduled to occur within 2 after last dose of study intervention. This is meant to limit participant burden.  
c Participants will be instructed to start taking study intervention the day following their Baseline visit, which will be Day 1. Study intervention will be taken in 
the morning without regard for food. 
d Participants are required to fast for safety laboratory tests at the Baseline Visit (Visit 2), Week 1 (Visit 3), Week 4 (Visit 5), Week 12 (Visit 9), Early 
Discontinuation (Visit 10), if applicable, and Safety follow‑up Visit (Visit 12). Participants are not required to fast for laboratory tests at the Screening Visit or 
Week 8 (Visit 7). 
e All SAEs will be followed until resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up (Section 8.4.3). 
CONFIDENTIAL
Page 27 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
28 
2.
INTRODUCTION
Fatty acid amide hydrolase (FAAH) is the primary enzyme responsible for catabolism of the 
endocannabinoid anandamide (AEA) (Cravatt 1996), an endogenous ligand for the type-1 
cannabinoid receptor (CB1). Inhibition of FAAH protects AEA from degradation leading to 
elevated levels of AEA (Kathuria 2003), and reduces fear and anxiety-related behaviors in 
rodents (Kathuria 2003; Patel and Hillard 2006; Haller 2009; Hill 2013; Bluett 2014; 
Haller 2014; Lomazzo 2015; Carnevali 2017).  
JZP150 (previously known as PF-04457845) is an orally available, highly selective and 
irreversible inhibitor of FAAH (Ahn 2011; Johnson 2011; Bonifacio 2020). A recent 
investigator-sponsored, placebo-controlled study showed that JZP150 enhanced recall of fear 
extinction memory and blunted negative affect in response to an aversive stimulus in healthy 
volunteers (Mayo 2020). Another study revealed that JZP150 significantly increased slow wave 
sleep as measured by polysomnography and improved self-reported overall self-reported sleep 
compared to placebo in men with cannabis use disorder (CUD) (D'Souza 2019).  
Taken together, results from previous studies in animals and humans suggest that FAAH 
inhibition with JZP150 may positively influence many of the core symptoms experienced by 
patients with posttraumatic stress disorder (PTSD). 
2.1. 
Study Rationale 
This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group study of the 
safety and efficacy of JZP150 in the treatment of adult participants with PTSD. JZP150 is an 
orally available, highly selective and irreversible inhibitor of FAAH. 
The purpose of this phase 2 study is to provide an evaluation of the efficacy and safety of 
JZP150 in participants with PTSD, while evaluating a broad range of JZP150 doses to support 
pharmacokinetic (PK)/pharmacodynamics (PD) exposure-response analysis. Results from this 
study will be used to inform the study design, patient population, and dose selection for future 
studies in PTSD. 
Multiple preclinical and clinical studies have demonstrated the association between the 
endocannabinoid system and the underlying pathophysiology of PTSD, which JZP150 directly 
targets (ie, augmentation of AEA levels).  
A double-blind, placebo-controlled experimental study examined the effect of JZP150 on 
experimentally induced fear conditioning and extinction, and stress response among healthy 
volunteers. Study participants on 4 mg JZP150 once daily (QD) compared to placebo had 
improved recall of fear extinction 24 hours later, and did not have the typical reduction in AEA 
in response to acute stress. Furthermore, those participants who were randomized to JZP150 had 
decreased stress-induced reactivity to emotional pictures demonstrating an attenuation of 
negative affect. 
Results from previous studies in animals and humans suggest that FAAH inhibition with JZP150 
may positively influence many of the core symptoms experienced by patients with PTSD. 
CONFIDENTIAL
Page 28 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
29 
2.2. 
Background 
Posttraumatic stress disorder is a common psychiatric condition that can result from direct or 
indirect exposure to actual or threatened death, serious injury or sexual violence (APA 2013). 
Approximately 70% of the global population will experience a traumatic event at some point 
during their lifetime, the majority of whom will recover in the days and weeks following trauma 
exposure (Kessler 2017). However, 4.7% to 6.1% will go on to develop PTSD in the US 
(Goldstein 2016), with similar rates observed across European Union countries (0.6 to 6.7%) 
(Burri and Maercker 2014). While men are more likely to experience a traumatic event, women 
are twice as likely to develop PTSD (Goldstein 2016; Kessler 2017).  
Posttraumatic stress disorder is characterized by symptoms experienced after a potentially 
traumatic event (Hoffman 2018). Symptoms of PTSD are grouped into 4 symptom clusters: 
1) recurrent intrusion/re-experiencing; 2) persistent avoidance; 3) negative alterations in mood 
and cognition; and 4) marked arousal/reactivity. A traumatic event is defined as exposure to 
actual or threatened death, serious injury, or sexual violence that is either directly experienced, 
witnessed, learned about the occurrence to a loved one, or extreme or repeated exposure to 
aversive details through work (ie, first responders) (APA 2013). In addition to increased risk for 
mortality, PTSD also has a significant impact on how patients feel and function. Posttraumatic 
stress disorder impacts all aspects of patients’ lives including negative impacts on work, school, 
relationships, housing, legal problems, financial problems and an overall increase in healthcare 
utilization and healthcare costs (Kessler 2017; Watson 2019). 
Various guidelines exist for the treatment of PTSD (APA 2004; NICE 2018; VA/DoD 2003; 
ISTSS 2018), most of which include guidance for both psychological and pharmacological 
treatments. There is an urgent need to address a critical gap in the advancement of 
pharmacotherapy treatment for PTSD (Krystal 2017). Food and Drug Administration 
(FDA) -approved medications for PTSD are limited to 2 selective serotonin reuptake inhibitors 
(SSRIs): sertraline and paroxetine. Both are thought to reduce symptom severity of PTSD 
through the same mechanism of action with many patients experiencing residual symptoms. Due 
to limited efficacy of approved medications, many providers turn to polypharmacy and off-label 
use of medications in order to address the range of debilitating symptoms that comprise PTSD. 
These medications and combinations of medications have not been adequately studied. The last 
20 years have been marked by a dearth of research into pharmacotherapies for PTSD despite a 
massive unmet medical need for a condition that results in significant morbidity and mortality. 
The endocannabinoid system is a neuromodulatory system comprised of 2 G-protein-coupled 
receptors (CB1 and type 2 cannabinoid receptor), 2 major endogenous lipid ligands (AEA and 
2-arachidonoylglycerol), and the enzymes involved in the synthesis and degradation of these 
lipid ligands (FAAH and monoacylglycerol lipase) (Hill 2018). Preclinical and translational 
work implicates the endocannabinoid system in the pathophysiology of PTSD and suggests the 
endocannabinoid system plays a critical role in stress responsivity, anxiety and fear extinction. 
Since FAAH is the primary enzyme responsible for the active degradation of AEA 
(Cravatt 1996), inhibition of FAAH represents a novel mechanistic approach for augmenting 
AEA levels at relevant brain circuits. Fatty acid amide hydrolase inhibition has been shown to 
reduce stress-induced anxiety and enhance the extinction of fear memory in animals 
(Kathuria 2003; Patel and Hillard 2006; Haller 2014; Hill 2013; Bluett 2014; Haller 2009; 
CONFIDENTIAL
Page 29 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
30 
Lomazzo 2015; Carnevali 2017) and humans (Hill 2009; Gunduz-Cinar 2013; Hauer 2013; 
Dincheva 2015; Harfmann 2020). 
The PK of JZP150 has been characterized in 3 phase 1 studies in a total of 76 healthy adult 
volunteers after single- (dose range 0.1 to 40 mg) and multiple-dose (dose range 0.5 to 8 mg QD) 
oral administration. Absorption of JZP150 was rapid, reaching maximal plasma concentrations 
within an average of 2 hours post dose. Plasma concentrations of JZP150 post maximum plasma 
concentration (Cmax) followed a multiphasic decline, with an estimated terminal half-life (t½) 
ranging from approximately 12 to 23 hours. The steady-state of plasma concentrations was 
attained by Day 7 following QD administration for 14 days with an approximate 2 to 3× 
accumulation in exposure between Days 1 and 14. The exposures of JZP150 at steady-state 
appeared dose-proportional over the dose range of 0.5 to 8 mg following multiple dose 
administration; but supra-proportional increases in exposure were noted over a similar dose 
range of 0.1 to 10 mg following single oral administration. Proportional increase of exposures 
was observed in the dose range of 10 to 40 mg following single dose administration. No major 
food effects on the PK of JZP150 were observed using a tablet formulation. Examination of the 
relationship between FAAH inhibition and JZP150 plasma concentration suggests that 
concentrations of at least 1 ng/mL is required to maintain FAAH inhibition by at least 97%. 
JZP150 has been evaluated in 7 sponsor-initiated interventional clinical studies to date. In these 
studies, a total of 108 healthy volunteers, 37 subjects with osteoarthritis and 8 subjects with 
PTSD have been administered 4 mg JZP150, which is the high end of the therapeutic dose range. 
There have been no deaths, serious adverse events (SAEs) or severe adverse events (AEs) in the 
completed sponsor-initiated interventional clinical studies in subjects who have received JZP150. 
The overall incidence and severity of AEs observed during these studies has been comparable to 
placebo. No maximum tolerated dose has been identified. There were no safety concerns 
suggested by laboratory values, vital signs, or electrocardiogram (ECG) data. Based on this 
experience, the overall safety and tolerance of JZP150 supports further clinical testing. 
In addition, 73 participants have been dosed with JZP150 in investigator-initiated research 
studies where the sponsor has provided compound to investigators. The longest duration study 
has been a 28-day study evaluating JZP150 4 mg QD in subjects with CUD. There have been no 
deaths, SAEs or severe AEs apart from 1 incidence each of severe fatigue, dizziness, and 
headache reported in these investigator-initiated research studies. 
 
 
 
A detailed description of the chemistry, pharmacology, efficacy, and safety of JZP150 is 
provided in the IB. 
CONFIDENTIAL
Page 30 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
31 
2.3. 
Benefit/Risk Assessment 
A summary of the benefit-risk assessment for conducting study JZP150-201 is provided in the 
subsections below. 
2.3.1. 
Risk Assessment 
Participants who enroll in this study may encounter the following potential risks: 
• Adverse events for participants in JZP150-201 are expected to be similar to those 
seen in previously conducted clinical studies with the high end of the dose range of 
JZP150 (ie, 4 mg). The most common treatment-emergent adverse events (TEAEs) 
that have occurred in ≥ 2participants on JZP150 and greater than placebo included 
headache, back pain, and dizziness. To date, JZP150 has been well-tolerated with an 
AE profile that is comparable to placebo. No deaths or SAEs have been reported in 
clinical studies with JZP150.  
 
 
 
 
 
 
 
 
 
• Participants will be asked to discontinue prohibited medications to enter the study, 
including those medications that could affect the evaluation of PTSD symptoms and 
those related to the pharmacology of JZP150. There may be risks associated with 
abrupt discontinuation of some of these medications. 
• Study procedure-related risks, including risks and/or discomfort associated with blood 
collection, ECGs, physical examinations, and completion of questionnaires and other 
assessments. 
2.3.2. 
Benefit Assessment 
Participants who enroll in this study may experience the following benefits: 
• Receiving JZP150 for the study duration may alleviate the significant symptom 
burden associated with PTSD. 
CONFIDENTIAL
Page 31 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
32 
• Contribution to the process of developing new therapies in PTSD. 
• Participants will receive comprehensive clinical exams and clinical monitoring 
associated with the study. 
• A future a long-term open-label study may become available for participants that 
complete this study. 
2.3.3. 
Overall Benefit: Risk Summary 
Benefits to participants include the potential to receive a therapy, which may alleviate symptoms 
of PTSD, contribute to the development of new therapeutics in PTSD, as well as receiving 
comprehensive physical examinations and clinical monitoring. 
Risks to all participants include those related to JZP150 and to blood collection and completion 
of clinical assessments and questionnaires. 
 
 
 
 The risks to 
subjects are expected to be similar to those seen in prior clinical studies, which are summarized 
in Section 2.2. 
More detailed information about the known and expected benefits and risks and reasonably 
anticipated AEs of JZP150 may be found in the IB and the informed consent document. 
CONFIDENTIAL
Page 32 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
33 
3. 
OBJECTIVES AND ESTIMANDS/ASSESSMENTS 
Objectives 
Estimands/Assessments 
Primary 
 
To evaluate the efficacy of JZP150 administered 
once daily for up to 12 weeks at doses of 0.3 mg 
and 4 mg compared to placebo in the treatment of 
adults with PTSD, as measured by the change in 
CAPS-5 total symptom severity score. 
The primary estimand is defined as follows: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo. 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
• 
Variable (endpoint): Clinician Administered 
PTSD Scale (CAPS-5) total symptom severity 
score change from Baseline to Week 12. 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in CAPS-5 
total symptom severity score for each 
treatment group and the difference in means 
between each randomized treatment group 
compared to placebo. 
Key Secondary 
 
To evaluate the efficacy of JZP150 administered 
once daily for 12 weeks at doses of 0.3 mg and 
4 mg compared to placebo on overall clinician 
and patient global impression of severity. 
The two key secondary estimands are defined as 
follows: 
Key Secondary Estimand 1: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo. 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
• 
Variable (endpoint): Change in Clinical 
Global Impression of Severity (CGI-S) from 
Baseline to Week 12. 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in CGI-S 
for each treatment group and the difference in 
means between each randomized treatment 
group compared to placebo. 
CONFIDENTIAL
Page 33 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
34 
Objectives 
Estimands/Assessments 
Key Secondary Estimand 2: 
• 
Treatment: 0.3 mg and 4 mg of JZP150, and 
placebo. 
• 
Population: Participants with PTSD (as 
defined in the eligibility criteria).  
• 
Variable (endpoint): Change in Patient 
Global Impression of Severity (PGI-S) from 
Baseline to Week 12. 
• 
Intercurrent events (ICEs): the “treatment 
policy strategy” will address all ICEs. 
• 
Population-level summary: The mean 
change from Baseline to Week 12 in PGI-S 
for each treatment group and the difference in 
means between each randomized treatment 
group compared to placebo. 
Secondary  
 
To evaluate the efficacy of JZP150 administered 
once daily for 12 weeks at doses of 0.3 mg and 
4 mg compared to placebo on functional 
outcomes and patient reported symptoms in adults 
with PTSD 
All other secondary and exploratory estimands are 
defined using the same estimand attributes 
(treatment, population, ICEs, and population-level 
summary, difference in means or proportions 
between each randomized treatment and placebo, 
as appropriate) as described above. The variables 
(endpoints) for the estimands are: 
• 
Responder analysis defined in 3 separate 
ways: 
o 
Percent of participants with ≥ 30% 
improvement on the CAPS-5 total 
symptom severity score from Baseline 
to Week 12 
o 
Percent of participants who are very 
much or much improved on the 
CGI-C at Weeks 4 and 12 
o 
Percent of participants with ≥ 1 unit 
of improvement on the PGI-S from 
Baseline to Week 12 
• 
CAPS-5 total symptom severity score change 
from Baseline to Week 4. 
• 
Change in functional outcomes measured by 
the Brief Inventory of Psychosocial 
CONFIDENTIAL
Page 34 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
35 
Objectives 
Estimands/Assessments 
Functioning (B-IPF) and Sheehan Disability 
Scale (SDS) from Baseline to Week 12.  
• 
Change in patient-reported symptoms of 
PTSD as assessed by the PTSD Checklist 
(PCL-5) from Baseline to Week 1, 4, 8, and 
12. 
• 
Change in patient and clinician-reported 
symptoms of PTSD as assessed by the PGI-S, 
and CGI-S from Baseline to Weeks 1, 4, and 
8. 
• 
Change in self-reported sleep problems as 
measured by the Insomnia Severity Index 
(ISI) and Pittsburgh Sleep Quality Index-
PTSD Addendum (PSQI-A) from Baseline to 
Week 12. 
• 
Change in PTSD symptom clusters (intrusive 
symptoms, avoidance symptoms, 
arousal/reactivity symptoms, and negative 
alterations in mood and cognition) as assessed 
by the change in the subscales of the CAPS-5 
from Baseline to Week 4 and Week 12. 
• 
Change in mood and anxiety from Baseline to 
Weeks 1, 4, and 12 as assessed by the Patient 
Health Questionnaire (PHQ-9), and change 
from Baseline to Weeks 4, 8, and 12 on the 
Structured Interview Guide for the Hamilton 
Anxiety Scale (SIGH-A). 
• 
Change in quality of life from Baseline to 
Week 12 as measured by the Recovering 
Quality of Life (ReQoL). 
To evaluate the safety and tolerability of JZP150 
administered once daily for up to 12 weeks at 
doses of 0.3 mg and 4 mg in adults with PTSD. 
The safety of JZP150 will be evaluated by the 
following assessments:  
• 
AEs 
• 
Vital signs 
• 
Physical examinations 
 
• 
12-lead ECG 
CONFIDENTIAL
Page 35 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
36 
Objectives 
Estimands/Assessments 
• 
Clinical laboratory tests (chemistry, 
hematology, urinalysis
 
 
• 
Columbia Suicide Severity Rating Scale 
(C-SSRS) 
• 
Withdrawal scale (marijuana withdrawal 
checklist) 
To characterize the PK and PD of JZP150 in 
adults with PTSD using population PK modeling 
and simulation methodology. 
Plasma concentration of AEA, JZP150 and its 
metabolites 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL
Page 36 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
37 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a 12-week, multicenter, double-blind, placebo-controlled, randomized, parallel-group 
study of the safety and efficacy of JZP150 in the treatment of adult participants with PTSD.  
Participants who meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
(DSM-5) criteria for PTSD as confirmed by the Mini International Neuropsychiatric Interview 
(MINI), with a total PCL-5 score ≥ 33 at Screening and Baseline will be eligible for enrollment. 
Following screening, eligible participants will be randomized (2:1:2) to 1 of 3 treatment arms: 
placebo, JZP150 0.3 mg QD, or JZP150 4 mg QD. Randomization will be stratified based on 
presence versus absence of use of stable selective SSRIs/ serotonin norepinephrine reuptake 
inhibitors (SNRIs) at Screening. The sponsor, study investigators, clinical raters, and participants 
will be blinded to treatment assignment.  
The study will consist of the following periods:  
• Screening period and washout of prohibited medications (up to 28 days). 
• Baseline and randomization (Day -1). 
• Double-blind Treatment Period (12 weeks). 
• Safety follow-up (2 weeks). 
Assessments of efficacy, safety, and PK will be conducted as indicated in Section 8.2 , 
Section 8.3, and Section 8.5, respectively, and as described in the Schedule of Activities (SoA) 
(Section 1.3). Study visits will be done in the clinic and with telephone call check-ins conducted 
between clinic visits.  
An independent data safety monitoring committee is not planned. An internal safety data review 
committee will review the accumulating safety data in a blinded manner (see Section 10.1.5 for 
details). 
4.2. 
Scientific Rationale for Study Design 
A 12-week, placebo-controlled, parallel-group, fixed-dose design of placebo and 2 doses of 
JZP150 was selected for the following reasons: 1) data obtained from this study design will 
inform the development, design, and dose selection for a phase 3 trial; 2) this study design has 
the potential to identify a no-effect or minimally effective dose and will characterize the efficacy 
and safety at the highest dose intended for clinical use and inform exposure-response; 3) this 
study and choice of control is in accordance with ICH E6(R2) and E10 guidelines; 4) the use of 
only 2 active treatment arms is expected to minimize placebo-related expectancy effects; 5) the 
12-week double-blind treatment duration was chosen to maximize active-placebo differences. 
The scientific rationale for key study design elements is provided below. 
Stratification Elements 
Randomization will be stratified by the presence or absence of concomitant use of SSRIs/SNRIs. 
Many PTSD patients are being treated with SSRI/SNRI medications and this enrollment strategy 
CONFIDENTIAL
Page 37 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
38 
is therefore reflective of the real-world patient populations. This enrollment strategy will permit 
assessment of safety and efficacy in both users and non-users of these antidepressants. 
Posttraumatic stress disorder diagnosis and severity of condition 
The PCL-5 cut score of ≥ 33 was selected for the following reasons: 1) The PCL-5 is a 20-item 
patient report measure that assesses the 20 DSM-5 symptoms of PTSD (Weathers 2013) and has 
a dynamic range of 0-80. The PCL is one of the most widely used self-report measures of PTSD 
and has strong internal consistency, test re-test reliability, and convergent and discriminant 
validity (Blevins 2015; Bovin 2016); 2) A PCL-5 total score ≥ 33 ensures patients are reporting 
significant symptoms especially as individuals may be enrolled that are currently on 
SSRIs/SNRIs and will minimize and potential “floor” effects; 3) The use of the PCL-5 limits the 
potential confounding factor of determining eligibility criteria using the same assessment that is 
used for the primary endpoints. The use of the PCL-5 to determine minimum symptom severity 
reduces this confound while using a measure that is valid and reliable with a strong correlation to 
total CAPS-5 scores (Weathers 2018); 4) Prior work has demonstrated that scores between 31 
and 33 are optimally efficient for diagnosing PTSD (Bovin 2016). Based on this range, the 
specific cut of ≥ 33 was selected as a conservative score based on this prior work, and from 
feedback obtained from PTSD clinical experts. 5) Relative to the CAPS-5, the PCL-5 is 
anticipated to minimize therapeutic alliance placebo effects. 
Study Duration 
The 12-week duration was selected for 3 main reasons. First, review of prior PTSD studies using 
the CAPS (CAPS-2 and CAPS-IV) efficacy endpoint have demonstrated a substantial placebo 
response. The pattern of this response shows a rapid increase in the mean placebo response from 
baseline to Week 4. After Week 4, the slope (Change in CAPS score vs. time) of this placebo 
response decreases, but the response continues to increase through Week 8. Between Week 8 and 
Week 12 the placebo response slope plateaus and in some cases the response decreases. This 
pattern has been observed in PTSD trials with sertraline and paroxetine. Based on this pattern of 
placebo response observed in prior PTSD trials, 12 weeks of treatment provides the best chance 
to observe separation between placebo and JZP150. Second, pivotal confirmatory trials will 
require at least 12 weeks of treatment. Therefore, setting up a phase 2 study with the same 
treatment duration de-risks phase 3. Third, 12-week treatment duration allows for maximizing 
the time between CAPS-5 assessments. 
Study Endpoints 
The primary efficacy assessment of this study is the CAPS-5, a structured clinical interview of 
patient reported severity of symptoms. The CAPS-5 is a well-established and validated 
assessment that captures DSM-5 symptoms of PTSD and is sensitive to treatment change. In 
addition, the key secondary endpoints (CGI-S and PGI-S) and exploratory endpoints are included 
to support and corroborate the clinical relevance of the primary endpoint. 
Clinic Visits/Telephone Calls and Study Assessments (Frequency of Collection) 
The primary evaluation for efficacy will be at the end of Week 12. A clinic visit is planned at 
Week 1 in order to conduct an early in clinic safety assessment and to ensure participants are 
dosing appropriately. This Week 1 assessment will also provide insight into the onset of effect 
with the assessment of the CGI-S, PGI-S and PCL-5 at this time point. A clinic visit will be 
CONFIDENTIAL
Page 38 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
39 
conducted at the end of Week 4 in order to allow for an evaluation of efficacy (including 
CAPS-5) and safety. The timing and number of administrations of the CAPS-5 has been 
carefully considered. Due to the therapeutic alliance that occurs with the administration of the 
CAPS-5, and the effect this can have on an already high placebo response rate, we have 
developed a CAPS-5 administration schedule to minimize the number of CAPS-5 
administrations during the study and to maximize the time between administrations. For this 
reason, the CAPS-5 is conducted only at Baseline, Week 4, and Week 12. A clinic visit at the 
end of Week 8 is also included for safety assessments, secondary efficacy assessments, sparse 
PK sampling and study intervention dispensation. 
4.3. 
Justification for Dose 
A low dose of 0.3 mg QD and high dose of 4 mg QD were selected for this phase 2 study. The 
selection of doses of JZP150 for use in PTSD was based on data assessing brain receptor 
occupancy in a positron emission tomography (PET) study conducted in healthy volunteers 
(Boileau 2015), PD data (ie, peripheral FAAH inhibition and elevation of plasma AEA 
concentrations) from clinical studies, and overall safety data. Clinical studies contributing data 
towards dose selection included single ascending and multiple ascending dose trials in healthy 
volunteers, a study conducted in participants with osteoarthritis of the knee, and a study in 
participants with CUD (D'Souza 2019). 
The inclusion of the 4 mg JZP150 dose is based on data obtained from PET imaging studies, the 
multiple ascending dose study, healthy volunteer fear conditioning trial and clinical studies in 
patients with osteoarthritis of the knee and CUD and the safety data obtained in studies 
conducted to date. Positron emission tomography imaging studies using a selective radioligand 
for imaging of brain FAAH binding availability conducted in healthy volunteers have shown 
JZP150 exhibits good brain penetration and selectively binds to FAAH yielding > 95% FAAH 
inhibition at single doses of 1, 4, and 20 mg (Boileau 2015; Rusjan 2018). In the PET study, 
doses of JZP150 were administered after completion of the baseline scan and approximately 
2 hours before the start of the blocking scan. JZP150 doses lower than 1 mg were not tested in 
this study and therefore the FAAH competitive binding dose-response was not established for 
doses lower than 1 mg. 
The 4 mg dose has shown therapeutic effects on fear extinction learning in a fear condition 
model conducted in healthy volunteers and this study data supports dose selection for this phase 
2 study. Data from studies conducted in participants with osteoarthritis of the knee, and 
participants with CUD (D'Souza 2019) at daily doses of 4 mg JZP150 showed average plasma 
AEA concentrations of 2.5 to 3 ng/mL. In the multiple ascending dose study in healthy 
volunteers, among those who received 4 mg JZP150 QD, individual plasma AEA concentrations 
at steady-state ranged from 2 to 4 ng/mL. A high dose of 4 mg JZP 150 QD is therefore selected 
for the planned phase 2 study and is expected to yield at least 97% FAAH inhibition and result in 
target plasma AEA concentrations higher than 2 to 2.5 ng/mL for the majority of participants. 
Moreover, based on the PET imaging study (Boileau 2015), doses higher than 4 mg are not 
expected to result in greater FAAH inhibition and subsequent higher plasma AEA levels. To 
date, single doses of JZP150 up to 40 mg, and repeated daily doses up to 8 mg, have been 
administered to healthy volunteers. Multiple daily doses of 4 mg have been administered for up 
to 30 days in patients with osteoarthritis and CUD. Overall JZP150 has been shown to be 
CONFIDENTIAL
Page 39 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
40 
well-tolerated with an AE profile comparable to placebo and no AEs suggesting a dose 
relationship were reported. In addition, no AEs related to abuse potential, cognitive impairment, 
or clinically meaningful changes in labs, vital signs, or ECGs were observed. Moreover, the 
exposure multiples across all the completed nonclinical safety studies indicate acceptable safety 
margins between the no-observed-adverse-effect levels (NOAELs) obtained in animals and the 
anticipated maximum human exposure at 4 mg QD. 
In single dose administration of 0.3 mg, JZP150 plasma levels were not above 1 ng/mL during 
most of the 24 hour period post dose; however, multiple dose administration of 0.5 mg QD 
resulted in mean plasma concentration levels in the 1 to 2 ng/mL range. Thus, based on these 
data and the observed between-subject variability, the 0.3 mg dose administered QD is not 
expected to maintain JZP150 plasma concentrations consistently above the threshold of 1 ng/mL 
to sustain the AEA levels at the target concentration above 2 to 2.5 ng/mL in most study 
participants. Therefore, the 0.3 mg dose should provide a means to identify a no-effect or 
minimally effective dose. Additionally, PTSD patients may have increased activity of FAAH and 
reduced levels of baseline AEA, and therefore may require higher AEA elevations compared 
with healthy volunteers. The 0.3 mg dose will also provide a low end of a broad range of 
concentrations to explore exposure-response. 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the last scheduled procedure shown in the SoA. 
The end of the study is defined as the date of the last visit of the last participant remaining in the 
study. 
CONFIDENTIAL
Page 40 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
41 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 to 70 years of age inclusive, at the time of signing the informed 
consent. 
Type of Participant and Disease Characteristics 
2. Participants must be outpatients with a primary diagnosis of DSM-5 defined PTSD 
confirmed by the MINI at Screening. 
3. PCL-5 total score ≥ 33 at Screening and Baseline. 
4. PTSD must be the primary diagnosis. Participants with comorbid diagnoses of major 
depressive disorder (with the exception of current severe symptoms), persistent 
depressive disorder (previously known as dysthymia), generalized anxiety disorder, 
specific phobia, obsessive compulsive disorder (with the exception of severe 
symptoms), or social anxiety disorder, are eligible if PTSD is the primary diagnosis. 
5. Participants prescribed an SSRI or SNRI must be on a stable dose for at least 8 weeks 
prior to screening with no plan to change dose or treatment regimen during the course 
of the trial. Those not on an SSRI/SNRI at screening may not start treatment with a 
SSRI/SNRI during the course of the study. See Section 6.8.1 for details. 
Weight 
6. Body Mass Index (BMI) from 18 to 40 kg/m2 (inclusive). 
Sex and Contraceptive/Barrier Requirements 
7.  Participant is male or female  
a. Male participants: 
Male participants are eligible to participate if they agree to the following during the study 
intervention period and for at least 30 days after the last dose of study intervention: 
• Refrain from donating sperm 
PLUS, either: 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent 
CONFIDENTIAL
Page 41 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
42 
OR 
•
Must agree to use contraception as detailed below
−
Agree to use a male condom with female partner use of an additional highly
effective contraceptive method with a failure rate of < 1% per year as described
in Appendix 5 OR should also be advised of the benefit for a female partner to
use a highly effective method of contraception as a condom may break or leak
when having sexual intercourse with a woman of childbearing potential who is
not currently pregnant during exposure to study intervention and for 30 days
after the last dose. Male participants with female partners must agree to use
double-barrier methods if the female is using oral contraception. Agree to use a
male condom when engaging in any activity that allows for passage of ejaculate
to another person.
b. Female participants:
•
A female participant is eligible to participate if she is not pregnant or breastfeeding,
and one of the following conditions applies:
−
Is a woman of non-childbearing potential (WONCBP) as defined in
Appendix 5.
OR
−
Is a woman of childbearing potential (WOCBP) and using a contraceptive
method that is highly effective, with a failure rate of < 1%, as described in
Appendix 5 during the study intervention period and for at least 30 days after
the last dose of study intervention. The investigator should evaluate the
potential for contraceptive method failure (eg, noncompliance, recently
initiated) in relationship to the first dose of study intervention. Female
participants must agree to use double-barrier methods if the female is using oral
contraception.
•
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) at Screening and Baseline before the first dose of
study intervention, see Section 8.3.5.
−
If a urine test cannot be confirmed as negative (eg, an ambiguous result), a
serum pregnancy test is required. In such cases, the participant must be
excluded from participation if the serum pregnancy result is positive.
•
Additional requirements for pregnancy testing during and after study intervention
are located in Section 8.3.5.
•
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
CONFIDENTIAL
Page 42 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
43 
Informed Consent 
8. Capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
9. Willing to provide contact information for at least 1 additional person the study team 
may contact.  
10. Willing and able to comply with the study schedule and other requirements. 
 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
Physical Health Conditions 
1. History or presence of gastrointestinal (including prior bariatric bypass surgery), or any 
other condition that, in the opinion of the investigator, may interfere with absorption, 
distribution, metabolism, or excretion of drugs. 
2.  Evidence of unstable or clinically significant systemic illness at screening including, 
but not limited to, the following:  
a. Cardiovascular disease (eg, unstable angina or congestive heart failure, chronic 
ventricular arrhythmia, uncontrolled hypertension, systolic blood pressure 
≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg [at screening or baseline], or 
QT interval corrected using Fridericia’s formula [QTcF] > 450 msec for men and 
> 470 msec for women); 
b. Respiratory disease (eg, chronic obstructive pulmonary disease requiring oxygen 
therapy or hospitalization in the last year); 
c. Neurologic disease (eg, adulthood seizure disorders); 
d. Hepatic disease (eg, hepatitis B or hepatitis C viral infection); 
e. Renal disease; 
f. Immunodeficiency (eg, human immunodeficiency virus infection); 
g. Malignancy diagnosed within 5 years prior to screening, with the exception of 
adequately treated localized skin cancer (basal cell or squamous cell carcinoma) or 
carcinoma in-situ of the cervix. 
3. Female participants who are pregnant, trying to become pregnant, nursing, or lactating 
and/or have a positive serum/urine human chorionic gonadotropin (hCG) test at 
Screening/Baseline, respectively.  
CONFIDENTIAL
Page 43 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
44 
4. History or presence of acute or unstable medical condition, behavioral or psychiatric 
disorder (other than PTSD), or surgical history that could affect the safety of the 
participant or interfere with study efficacy, safety, PK assessments, or the ability of the 
participant to complete the trial based on the judgment of the investigator. 
Mental Health Conditions 
5. Any suicidal behavior in the past 2 years as assessed on the C-SSRS or active suicidal 
ideation in the past 6 months defined as endorsing item 4 or 5 on the C-SSRS. 
6. History or current bipolar disorder, bipolar related disorders, active psychotic 
symptoms, schizophrenia, schizophrenia spectrum disorders, according to DSM-5 
criteria. 
7. A recent major depressive episode (onset within the past 6 months) by history or a 
diagnosis of current severe symptomatic Major Depressive Disorder as assessed by the 
MINI and a PHQ-9 score > 20 at Screening. 
Trauma-related Factors 
8. Ongoing exposure to a traumatic event or exposure to a traumatic event <3 months 
prior to Screening. 
9. Index event that occurred > 12 years prior to screening. 
10. Index event is combat trauma (combat within a war zone). 
11. Receiving disability payments because of PTSD or any other psychiatric disorders. 
12. Engaged in litigation whereby personal compensation could be gained from having 
prolonged symptoms of PTSD or any other psychiatric disorder. 
13. Individual meets criteria for dissociative subtype of PTSD as defined by DSM-5. 
Substance Use 
14. Current or recent (within the past 6 months) diagnosis of a substance use disorder 
(including cannabis use disorder) based on DSM-5 criteria with the following 
exceptions and limitations 
a. Caffeine use disorder (limitation: see exclusion #16 below) 
b. Tobacco use disorder (limitation: see exclusion #17 below) 
c. Mild alcohol use disorder (as defined by DSM-5 criteria)  
15. Current, recent (within the past 6 months), or seeking treatment for a substance-related 
disorder. The use of Narcotics Anonymous/ Alcoholics Anonymous is acceptable if 
being used for maintenance of sobriety. 
16. Inability to limit caffeine use to ≤ 600 mg/day throughout the study. 
17. Inability to abstain from nicotine products during normal sleep periods. 
18. Current (past 6 months) regular use of cannabis is excluded. Sporadic recreational 
users of cannabis can complete a repeat urine drug screen during the Screening period. 
CONFIDENTIAL
Page 44 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
45 
If this is negative, the participant may be allowed to enter the study pending agreement 
to completely refrain from the use of cannabis during the course of the study. 
Prior/Concomitant Therapy 
19. Participants who plan to begin or are currently enrolled in, an evidence-based 
psychotherapy for the treatment of PTSD. Examples include: prolonged exposure; 
cognitive processing therapy; trauma-focused cognitive behavioral therapy; eye 
movement desensitization and reprocessing therapy; Skills training in affective and 
interpersonal regulation; Concurrent treatment of PTSD and substance use disorders 
using prolonged exposure, or an evidence-based digital therapeutic for the treatment of 
PTSD or associated symptoms (eg, Nightware). 
20. Use of prohibited prescription and/or non-prescription drugs and other products. See 
Section 6.8 for details. 
Prior/Concurrent Clinical Study Experience 
21. Prior exposure to JZP150 (previously known as PF-04457845) or participation in a 
prior clinical trial of PF-04457845. 
22. Received an investigational drug in the past 30 days or 5 half-lives prior to Screening 
(whichever is longer), or plans to use an investigational drug (other than the study 
intervention) during the study. 
Diagnostic Laboratory Assessments 
23. Clinically significant abnormal laboratory values as assessed by the investigator 
(clinical chemistry, hematology, and urinalysis), including creatinine clearance 
(CrCL) < 60 mL/min per Cockcroft-Gault Equation, total bilirubin > 1.5 × upper limit 
of normal (ULN) (isolated), alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2 × ULN (isolated), or ALT or AST > 1 × ULN and have a 
total bilirubin > 1 × ULN. An isolated total bilirubin > 2 × ULN attributable to known 
Gilbert syndrome is not exclusionary. Note: Screening laboratory tests may be repeated 
1 time. 
24. Urine drug screen positive at screening for cocaine, amphetamines, methamphetamine, 
barbiturates, benzodiazepines, opioids, methadone, THC, MDMA, PCP, LSD, except 
for prescribed drugs at Screening that will be washed out prior to Baseline. 
25. Positive alcohol breath test at screening. 
Other Exclusions 
26. Does not agree to refrain from consumption of food/food products containing seville 
oranges, grapefruit, pomelos, tangelos, or grapefruit hybrids from 2 weeks before the 
start of study intervention until after the final dose. 
CONFIDENTIAL
Page 45 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
46 
27. Allergy or sensitivity to any ingredients in the study intervention formulation or 
placebo. 
28. Any other condition and/or situation that causes the investigator or medical monitor to 
deem the participant unsuitable for the study. 
 
 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
1. Refrain from consumption of food/food products containing seville oranges, grapefruit, 
pomelos, tangelos, or grapefruit hybrids from 2 weeks before the start of study 
intervention until after the final dose. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
As noted in exclusion criteria 14 through 18 (Section 5.2 ), participants are excluded from the 
study for the following criteria: 
1. Current or recent (within the past 6 months) diagnosis of a substance use disorder 
(including cannabis use disorder) based on DSM-5 criteria with the following exceptions 
and limitations 
a. Caffeine use disorder (limitation: see exclusion #16, above) 
b. Tobacco use disorder (limitation: see exclusion #17, above) 
c. Mild alcohol use disorder (as defined by DSM-5 criteria)  
2. Current, recent (within the past 6 months), or seeking treatment for a substance-related 
disorder. The use of Narcotics Anonymous/ Alcoholics Anonymous is acceptable if being 
used for maintenance of sobriety. 
3. Inability to limit caffeine use to ≤ 600 mg/day throughout the study. 
4. Inability to abstain from nicotine products during normal sleep periods. 
5. Current (past 6 months) regular use of cannabis is excluded. Sporadic recreational users 
of cannabis can complete a repeat urine drug screen during the Screening period. If this is 
negative, the participant may be allowed to enter the study pending agreement to 
completely refrain from the use of cannabis during the course of the study.  
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to receive study intervention. A minimal set of screen 
failure information is required to ensure transparent reporting of screen failure participants to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and 
to respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details (ie, reason for screen failure), eligibility criteria, and any SAE. 
CONFIDENTIAL
Page 46 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
47 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once. Individuals may not rescreen for eligibility criteria related to PTSD diagnostic 
status or the severity of their PTSD (eg, PCL-5 score). Rescreened participants should be 
assigned a new participant number for every screening/rescreening event. 
5.5. 
Criteria for Temporarily Delaying Administration of Study 
Intervention Administration 
As indicated in Section 6.5 , dose modifications are not permitted. See Section 7.1 for details 
regarding temporary interruption of study intervention. 
CONFIDENTIAL
Page 47 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page  
CONFIDENTIAL 
48 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
Study intervention/treatment is defined as any investigational intervention(s), marketed 
product(s), or placebo intended to be administered to a study participant according to the study 
protocol. 
6.1. 
Study Intervention(s)/Treatment(s) Administered 
Participants will be instructed to take study intervention in the morning QD without regard for 
food. The study interventions planned for use in this study are described in Table 4 below. 
CONFIDENTIAL
Page 48 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
Page 49 
CONFIDENTI 
Table 4: 
Study Treatment/Intervention 
Treatment 
Arm 
Intervention/Treatment 
Name 
Formulation 
Unit Dose 
Strength(s) 
Dosage 
Level(s) 
Route of 
Administration 
Use 
Sourcing 
Packaging 
Labeling 
Storage 
Conditions 
1 
Placebo 
Capsule 
Placebo 
QD 
Oral 
Placebo 
Provided 
centrally 
by the 
Sponsor 
Bottles with 
30 capsules/ 
bottle 
Double-
blind 
2 
JZP150  
Capsule 
0.3 mg 
QD 
Oral 
Experimental 
Provided 
centrally 
by the 
Sponsor 
Bottles with 
30 capsules/ 
bottle 
Double-
blind 
3 
JZP150 
Capsule 
4 mg 
QD 
Oral 
Experimental 
Provided 
centrally 
by the 
Sponsor 
Bottles with 
30 capsules/ 
bottle 
Double-
blind 
Abbreviations: mg = milligram; QD = once daily. 
CONFIDENTIAL
Page 49 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
6.2. 
Preparation/Handling/Storage/Accountability 
Further guidance and information for the final disposition of unused study interventions are 
provided in the Investigator Trial Site Binder. 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized site 
staff. Details regarding dispensation and storage requirements for study intervention are provided 
in the pharmacy manual. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (ie, 
receipt, reconciliation, and final disposition records). 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants who sign the ICF will receive a participant number. The participant number 
identifies the participant for all study procedures that occur throughout the study. This number is 
unique and once assigned, cannot be reassigned to another study participant.  
Treatment allocation/randomization for this study will occur centrally through the use of an 
interactive response technology (IRT). Following screening, eligible participants will be 
randomized (2:1:2) to one of three treatment arms: placebo, JZP150 0.3 mg QD, or JZP150 4 mg 
QD. Randomization will be stratified based on presence versus absence of stable use of 
SSRIs/SNRIs at Screening. The sponsor, study investigators, study coordinators, site staff, 
clinical raters, and participants will be blinded to treatment assignment. 
A double-blind approach will be used throughout the 12-week treatment period. During the 
study, the number of capsules taken each day will be the same for participants randomized to 
each treatment and JZP150 and placebo capsules will look and feel identical. 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a participant’s 
intervention assignment unless this could delay emergency treatment of the participant.  
If a participant’s intervention assignment is unblinded, the sponsor must be notified within 
24 hours after breaking the blind. The date and reason that the blind was broken must be 
recorded in the source documentation and case report form, as applicable. The participant’s 
treatment assignment may be unblinded for regulatory reporting purposes. Notification of the 
treatment assignment is only made known to those who require it for safety reporting and 
submission processes. All other individuals involved in the study, including the investigator, will 
CONFIDENTIAL
Page 50 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
remain blinded to treatment assignment. Participants for whom the blind is broken for this reason 
will not be withdrawn from the study.  
Sponsor safety staff may unblind the intervention assignment for any participant with an SAE. If 
the SAE requires that an expedited regulatory report be sent to one or more regulatory agencies, 
a copy of the report, identifying the participant’s intervention assignment, may be sent to 
investigators in accordance with local regulations and/or sponsor policy.  
6.4. 
Study Intervention/Treatment Compliance 
When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by direct questioning, 
counting returned capsules, etc. during the site visits and documented in the source documents 
and case report form (CRF) or other electronic device as applicable. Deviation(s) from the 
prescribed dosage regimen should be recorded. 
A record of the quantity of JZP150 dispensed to and administered by each participant must be 
maintained and reconciled with study intervention and compliance records. Intervention start and 
stop dates, including dates for study intervention delays should also be recorded in the CRF or 
other electronic device as applicable. 
This study will use a medication adherence monitoring platform for all participants in the study. 
The Platform is provided on a smartphone application to confirm ingestion of study intervention. 
Built-in reminders and a communication system allow real-time intervention in case of missed 
doses. Other features such as visit reminders, study-specific instructions, and questionnaires may 
be included. 
6.5. 
Dose Modification 
No dose adjustments or modifications will be allowed. Participants who cannot tolerate their 
assigned fixed dose of JZP150 will be discontinued from the study intervention (see Section 7.1).  
6.6. 
Continued Access to Study Intervention After the End of the Study 
No immediate long-term study is planned. A future a long-term open label study may become 
available for participants that complete this study. 
6.7. 
Treatment of Overdose, Medication Errors, or Misuse 
Any dose greater than the assigned QD dosing will be considered an overdose. In a case of an 
acute overdose, there is no specific antidote but treatment should consist of general supportive 
measures. See the JZP150 IB for further details. 
In the event of an overdose, the investigator/treating physician should: 
• Contact the Medical Monitor immediately. 
• Evaluate the participant to determine, in consultation with the Medical Monitor, 
whether study intervention should be interrupted. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until at 
least 14 days after the last dose of study intervention. 
CONFIDENTIAL
Page 51 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
• Document the quantity of the excess dose as well as the duration of the overdose. 
6.8. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) or other specific categories of interest that the 
participant is receiving at the time of enrollment or receives during the study must be recorded 
along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Psychoactive medications that could affect the evaluation of symptoms of PTSD (with the 
exception of insomnia symptoms) are prohibited within a time period prior to Baseline, 
corresponding to at least 5 half-lives of the drug(s) or planned use of such drug(s) at some point 
throughout the duration of the study. Psychoactive medications that do not affect the evaluation 
of PTSD symptoms (including psychoactive medications used to manage insomnia) should be 
stable for at least 6 weeks prior to Screening and remain stable over the course of the trial with 
the exception of SSRI/SNRIs which is described in detail in Section 6.8.1, below. 
For details on prohibited and cautionary medications please refer to the Prohibited and 
Cautionary Medication document that has been provided. 
Prohibited/cautionary medications and other products include the following. Note: An example 
list of prohibited/cautionary medications is provided in the Investigator Trial Site Binder: 
Prohibited: 
• Prescription or nonprescription drugs or other products (eg, St. John’s Wort) known 
to be strong or moderate inducers of CYP3A4, which cannot be discontinued at least 
4 weeks before baseline, or planned use at any time during the study.  
• Use of prescription or nonprescription drugs or other products (eg, grapefruit, 
grapefruit juice, or Seville oranges) known to be strong or moderate inhibitors of 
CYP3A4, which cannot be discontinued 2 weeks or 5 half-lives, whichever is longer, 
before baseline or planned use at any time during the study. 
Cautionary: 
• Use of prescription drugs that are CYP3A4 substrates at any time during the study.  
6.8.1. 
Use of Concomitant SSRIs/SNRIs  
Participants who are stable on SSRI/SNRIs as well as those not on concomitant SSRI/SNRIs at 
Screening may be enrolled in the study, as follows: 
• Participants on an SSRI/SNRI at Screening may stay on the SSRI/SNRI as long as the 
following criteria are met: (1) the SSRI/SNRI is not a prohibited medication (eg, 
CONFIDENTIAL
Page 52 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
fluvoxamine; see the prohibited medication list in the Investigator Trial Site Binder), 
(2) the dosing regimen remains stable with no plans to change during the course of 
the trial, and (3) the PTSD severity criteria outlined in the eligibility criteria 
(Section 5) are still met. The use of tricyclic antidepressants are prohibited. 
• Participants not on an SSRI/SNRI at screening will also be enrolled as long as 
treatment with an SSRI/SNRI is not initiated during the course of treatment.  
CONFIDENTIAL
Page 53 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation from study intervention does not represent discontinuation from the study 
(Section 7.2). Participants may discontinue from study intervention at any time for any reason, or 
at the discretion of the investigator. In addition, a participant may be withdrawn from study 
intervention by the investigator or sponsor for safety, behavioral, compliance, and/or 
administrative reasons.  
For participants that discontinue study intervention, all effort should be made to complete the 
procedures listed in the Early Discontinuation Visit, Efficacy Follow-up Visit (if applicable), and 
Safety Follow-up Visit (Section 1.3). If the participant does not withdraw from the study, 
continue to follow the participant as detailed in the SoA (Section 1.3).  
7.1. 
Discontinuation of Study Intervention 
In some instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will be requested 
to remain in the study and be asked to complete a 12-week efficacy follow-up. See the SoA for 
data to be collected at the time of discontinuation of study intervention and follow-up and for any 
further evaluations that need to be completed. Every effort should be made to have the 
participant attend an Early Discontinuation Visit and the Week 12 efficacy follow-up. For those 
participants who discontinue study intervention prior to Week 4, every effort should be made to 
have the participant complete the efficacy follow-up at Week 4 and Week 12 (see Section 1.3). 
A participant must be discontinued from study intervention for any of the following reasons, or if 
they meet protocol stopping criteria: 
• The participant requests to discontinue study intervention. 
• The participant has an AE that may compromise the participant’s continued 
participation. 
• The participant has a suicide risk reported or assessed by the C-SSRS that requires 
intervention (Section 8.3.6). 
• The participant has a positive pregnancy test (Appendix 5 and Section 8.4.5). 
• The participant is noncompliant with study intervention or procedures. 
• The participant meets the liver chemistry stopping criteria (Section 7.1.1).  
• The participant meets the QTc stopping criteria (Section 7.1.2). 
• 
 
• The sponsor decides to terminate the study prior to completion. 
• The investigator determines the participant should not continue on study intervention. 
CONFIDENTIAL
Page 54 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
7.1.1. 
Liver Chemistry Stopping Criteria 
Discontinuation of study intervention for abnormal liver tests is required by the investigator 
when a participant meets one of the conditions outlined in Appendix 7 or in the presence of 
abnormal liver chemistries not meeting protocol-specified stopping rules if the investigator 
believes that it is in best interest of the participant. 
7.1.2. 
QTc Stopping Criteria 
If a clinically significant finding is identified in a particular study participant (including, but not 
limited to a measured QT interval corrected using QTcF of > 500 msec) after enrollment and 
confirmed with a repeat (second) ECG, the investigator or qualified designee will discontinue the 
participant from the study and arrange for appropriate follow-up, including repeat ECGs as 
indicated. This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE. 
7.1.3. 
 
 
 
 
 
 
 
7.1.4. 
Temporary Discontinuation/Study Intervention Interruption 
If a participant must temporarily interrupt study intervention for any reason, the Medical Monitor 
should be consulted to determine whether the participant will continue in the study. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, or compliance 
reasons. This is expected to be uncommon. 
If the participant is discontinued from study intervention, they will be asked to continue with 
follow-up efficacy visits. In this case, the participant will undergo the efficacy follow-up, as 
shown in the SoA (Section 1.3) and described in Section 7.1. 
If the participant is discontinued both from the study intervention, which will be returned to the 
clinical site, and from the study, an early discontinuation visit should be conducted (if possible) 
at the time of discontinuation, as shown in the SoA (Section 1.3). Refer to the SoA (Section 1.3) 
for data to be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
CONFIDENTIAL
Page 55 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
7.3. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible. 
• The site must counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the participant wishes to and/or should 
continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). After trying to contact the participant, the 
investigator should reach out to the contact provided by the participant. These contact 
attempts should be documented in the participant’s medical record.  
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study and lost to follow-up.  
− The participant is not considered lost to follow-up until the last scheduled visit for 
that individual participant.  
− The amount of missing data for an individual participant will be managed via the 
data handling guidelines for the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Study and Site 
Start and Closure Section 10.1.9. 
CONFIDENTIAL
Page 56 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Efficacy, safety, PK/PD sampling will be collected during clinic visits as outlined in the SoA. In 
addition, telephone calls will be conducted between clinic visits in order to (1) assess safety and 
(2) maintain engagement with the participants to mitigate attrition rates which are high in this 
patient population.  
Study procedures and their timing are summarized in the SoA (Section 1.3).  
For clinic visits, participants should check-in to the study site in the morning, with the exception 
of the Week 8 visit, which should be scheduled for the afternoon/ evening. Participants should 
dose at home in the morning on the day of the Week 8 clinic visit. The investigator may opt to 
have the participant attend an unscheduled visit, if deemed necessary, at any time during the 
study. Some clinic visits may be shortened and/or conducted remotely, if required due to the 
COVID-19 (or other) pandemic, and with approval from the Sponsor’s Medical Monitor, as 
noted in the SoA (Section 1.3). Protocol waivers or exemptions are not allowed.  
All screening evaluations must be completed by the principal investigator (PI) or 
sub-investigator and reviewed to confirm that potential participants meet all eligibility criteria. 
The investigator should maintain a screening log to record details of all participants screened and 
to confirm eligibility or record reasons for screening failure, as applicable. 
After screening procedures have been completed and eligibility criteria have been confirmed, 
eligible participants will be provided with instructions on how to discontinue any excluded 
medications. It should be documented that the investigator has determined that discontinuation is 
safe and medically appropriate, and the discontinuation is medically supervised. The medical 
monitor should be contacted if there are any questions regarding discontinuation of excluded 
medications. 
For clinical outcome assessment measures that are rated by specially qualified and trained 
interviewers/raters, the same person should perform each assessment for the same participant 
throughout the duration of the study, whenever possible. 
The CAPS-5 assessment will be administered and scored by a trained rater at the site throughout 
the study. Raters are defined as clinical site personnel (eg, a physician, clinical psychologist, or 
nurse) who must have undergone the required training in administration and scoring of the 
CAPS-5 and received certification to administer the CAPS-5. Appropriate training for rating 
scales will be provided by the rater training vendor. Documentation of how and when data are 
filed, stored and transmitted to or from the study site will be provided in the Investigator Trial 
Site Binder. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the SoA. 
Pharmacokinetic results that could unblind the study will not be reported to investigative sites or 
other blinded personnel until the study has been unblinded. The maximum amount of blood 
collected from each participant over the duration of the study (18 weeks) will be 108 mL. Repeat 
or unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
CONFIDENTIAL
Page 57 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
8.1. 
General Administrative Procedures 
8.1.1. 
Informed Consent 
The investigator or medically qualified designee (consistent with local requirements) must obtain 
documented consent from each potential participant prior to participation in this study. A signed 
copy of ICF should be given to the participant and the original should be placed in the 
participant’s medical records.   
8.1.2. 
Assignment of Participant Number 
Each participant who signs the ICF will be assigned a unique number that will identify the 
participant throughout the study. Once a number has been assigned, it cannot be reassigned to 
another study participant. 
8.1.3. 
Medical History 
A medical history will be obtained by the investigator or a medically qualified designee 
(consistent with local regulations). All active conditions should be recorded and any condition 
diagnosed within the participant’s lifetime that the investigator deems clinically significant. The 
information will include, but is not limited to, symptoms of PTSD (current and past, including 
symptoms experienced prior to any PTSD treatment); history and treatment (if any) of 
cardiovascular, pulmonary, gastrointestinal, 
 hepatic, renal, immunologic, 
neurologic, or psychiatric disease; reproductive status; current contraceptive method (if 
appropriate); smoking status (current/past), and confirmation of relevant inclusion and exclusion 
criteria. 
8.1.4. 
Medication Review (Prior and Concomitant Medications) 
The investigator or medically qualified designee should review the participant’s prior medication 
use within 30 days, with the exception of SSRI/SNRIs which will be assessed per eligibility 
criteria (Section 5). Medication that is required to be washed out prior to the study should also be 
recorded. All medication currently taken by the participant should be recorded.  
COVID-19 vaccination information will be collected as a concomitant medication, if the vaccine 
was obtained in the past 12 months. 
Additional information related to any medications or psychological treatment taken for the 
treatment of PTSD since diagnosis (eg, treatment duration, satisfaction) should be collected. 
8.1.5. 
Inclusion and Exclusion Criteria Review 
All inclusion and exclusion criteria should be reviewed by the PI (MD/DO) or sub-investigator 
(MD/DO) to ensure that the participant qualifies for the study. 
CONFIDENTIAL
Page 58 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8.1.6. 
Timing of Study Intervention Dosing 
Participants will be instructed to take study intervention in the morning QD without regard for 
food, with the exception of days of clinic visit where they will dose in clinic. The Week 8 visit is 
an afternoon visit and participants will take study intervention at home as normal on this visit 
day. 
8.1.7. 
Mini International Neuropsychiatric Interview (MINI) 
The Mini International Neuropsychiatric Interview (MINI) is a short, structured, clinician 
administered, diagnostic interview for psychiatric disorders (Sheehan 1998). This assessment 
will be used to confirm PTSD diagnosis at Screening. 
A sample MINI can be found in the Investigator Trial Site Binder. 
8.1.8. 
Life Events Checklist (LEC) 
The Life Events Checklist (LEC) is a measure designed to screen for potentially traumatic events 
in a respondent’s lifetime (Gray 2004). The LEC assesses exposure to events known to 
potentially result in PTSD or distress. This assessment will be used at the Screening visit only. 
A sample LEC can be found in the Investigator Trial Site Binder. 
8.2. 
Efficacy Assessments 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). 
8.2.1. 
Clinician Administered PTSD Scale (CAPS-5) 
The CAPS-5 is a structured, clinician administered, clinical interview wherein participants report 
on their symptoms of PTSD (Weathers 2018). The CAPS-5 will be administered by qualified 
medical personnel (ie, PI, clinical rater). It is a well-established, widely used, and validated 
assessment that captures PTSD symptom frequency and intensity over the past week using a 
5-point Likert-type rating scale. Its distinctive features include standardized prompts, assessment 
of symptom frequency, intensity, severity and behaviorally anchored ratings. 
A sample CAPS-5 can be found in the Investigator Trial Site Binder. 
8.2.2. 
Clinical Global Impression of Severity (CGI-S) 
The CGI-S will be assessed by qualified medical personnel (ie, PI, clinical rater) to evaluate the 
severity of participants’ PTSD. 
The CGI-S is a 7-point Likert-type rating scale and a widely used assessment in clinical 
psychopharmacology trials to assess severity of illness (Guy 1976). The responses to this 
investigator-completed scale range from 1 (Normal, not at all ill) to 7 (Among the most 
extremely ill patients). The qualified medical personnel will rate his/her impression of the 
severity of the participant’s current ability to function due to their PTSD relative to his/her 
experience with this patient population. 
A sample CGI-S can be found in the Investigator Trial Site Binder. 
CONFIDENTIAL
Page 59 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
 
8.2.3. 
Clinical Global Impression of Change (CGI-C) 
The CGI-C will be assessed by qualified medical personnel (ie, PI, clinical rater). The CGI-C is a 
7-point Likert-type rating scale and a widely used assessment to assess efficacy in clinical drug
trials (Guy 1976). Investigators or trained raters will rate their impression of any change in the
severity of the participant’s condition since Baseline on a 7-point scale ranging from 1 (very
much improved) to 7 (very much worse). Ratings will focus on the participants’ change in their
ability to function due to PTSD.
A sample CGI-C can be found in the Investigator Trial Site Binder. 
8.2.4. 
Patient Global Impression of Severity (PGI-S) 
The PGI-S is a 5-point Likert-type rating scale and a widely used assessment in clinical 
psychopharmacology trials to assess severity of illness. The responses of this patient-completed 
scale range from 1 = none to 5 = very severe. Participants will report on the severity of their 
PTSD symptoms. 
A sample PGI-S can be found in the Investigator Trial Site Binder. 
8.2.5. 
Brief Inventory of Psychosocial Functioning (B-IPF) 
The B-IPF is a 7-item self-reported questionnaire that assesses PTSD-related psychosocial 
functional impairment (Kleiman 2020). Questions regarding functional impairment are rated on a 
7-point scale from 0 (Not at all), 1 to 5 (Somewhat), to 6 (Very much).
A sample B-IPF can be found in the Investigator Trial Site Binder.
8.2.6. 
Sheehan Disability Scale (SDS) 
The SDS is a brief, 5-item self-reported tool that assesses functional impairment in work/school, 
social life, and family life (Leon 1997). The total score is 0 to 30 (0 unimpaired, 30 highly 
impaired). High scores are associated with significant functional impairment. 
A sample SDS can be found in the Investigator Trial Site Binder. 
8.2.7. 
PTSD Checklist (PCL-5) 
The PCL-5 is a 20-item self-reported measure that assesses the 20 DSM-5 symptoms of PTSD. It 
can be used for monitoring symptom change during and after treatment (Blevins 2015). 
A sample PCL-5 can be found in the Investigator Trial Site Binder. 
8.2.8. 
Insomnia Severity Index (ISI) 
The ISI is a 7-item self-reported questionnaire assessing the nature, severity, and impact of 
insomnia (Morin 2011). The dimensions evaluated are: severity of sleep onset, sleep 
maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep 
difficulties with daytime functioning, noticeability of sleep problems by others, and distress 
caused by the sleep difficulties. A 5-point Likert scale is used to rate each item. 
A sample ISI can be found in the Investigator Trial Site Binder. 
CONFIDENTIAL
Page 60 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
 
8.2.9. 
Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI-A) 
The PSQI-A is a 19-item self-report questionnaire evaluating sleep quality and disturbances over 
the past month (Insana 2013). The PSQI-A is comprised of seven different sleep disturbance 
items that are commonly reported by adults with PTSD (eg, hot flashes, memories or nightmares 
of the traumatic experience, and episodes of terror during sleep). Items are rated on a 0 (not in 
the past month) to 3 (three or more times a week) point scale and can be summed to create a total 
score. The total scores can range from 0 (normal) to 21 (severe). 
A sample PSQI-A can be found in the Investigator Trial Site Binder. 
8.2.10. 
Patient Health Questionnaire (PHQ-9) 
The PHQ-9 is a component of the longer Patient Health Questionnaire and is a concise, 
self-administered tool for assessing depression (Kroenke 2001). It incorporates DSM depression 
criteria with other leading major depressive symptoms into a brief self-report instrument that is 
commonly used for screening and diagnosis, as well as selecting and monitoring treatment. 
A sample PHQ-9 can be found in the Investigator Trial Site Binder. 
8.2.11. 
Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) 
The SIGH-A is a clinician administered rating scale developed to measure the severity of anxiety 
symptoms (Hamilton 1959). The scale consists of 14 items, each defined by a series of 
symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and 
somatic anxiety (physical complaints related to anxiety). 
A sample SIGH-A can be found in the Investigator Trial Site Binder. 
8.2.12. 
Recovering Quality of Life (ReQoL) 
The ReQoL-10 is a patient reported outcome that has been developed to assess the quality of life 
for people with different mental health conditions (Keetharuth 2018). It is suitable for use across 
all mental health populations including common mental health problems. 
A sample ReQoL can be found in the Investigator Trial Site Binder. 
8.3. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.3.1. 
Physical Examinations 
A complete PE will include, at a minimum, assessments of the cardiovascular, respiratory, 
gastrointestinal (including liver), neurological systems
 
. Height and weight will also be measured and recorded as indicated in the SoA 
(Section 1.3).  
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Any abnormalities identified at the screening PE should be recorded as medical history.  
CONFIDENTIAL
Page 61 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
 
8.3.2. 
Vital Signs 
Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed at each clinic 
visit, as indicated in the SoA (Section 1.3). 
Blood pressure and pulse measurements will be assessed with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the 
participant in a quiet setting without distractions (eg, television, cell phones). Respiratory rate 
and body temperature will be assessed after the participant has been resting and seated (or 
supine) for at least 5 minutes. 
Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse and 
3 blood pressure measurements (3 consecutive blood pressure readings will be recorded at 
intervals of at least 1 minute). The average of the 3 blood pressure readings will be recorded. The 
triplicate blood pressure measurements may be repeated once at Screening and Baseline. 
8.3.3. 
Electrocardiograms 
Triplicate 12-lead ECGs will be obtained as outlined in the SoA (see Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected 
QT (QTc) intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and any additional QTc 
readings that may be necessary. 
Electrocardiograms will be reviewed, initially interpreted, signed, and dated by the investigator 
or a designated physician after each ECG collection. All ECGs (with the exception of ECGs for 
participants who are screen failures) will be transmitted to a designated central ECG laboratory. 
A cardiologist at the central ECG laboratory will conduct a full over-read. A report based on data 
from this over-read will be issued to the site. 
8.3.4. 
Clinical Safety Laboratory Assessments 
See Appendix 3 for the list of clinical laboratory tests to be performed and to the SoA 
(Section 1.3) for the timing and frequency. 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports must 
be filed with the source documents.  
Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant unless judged by the investigator to be more severe than expected for the 
participant’s condition. 
All laboratory tests with abnormal values considered clinically significant during participation in 
the study (and considered by the investigator to be related to study intervention) should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or medical monitor. 
CONFIDENTIAL
Page 62 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
 
If clinically significant values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor notified. 
All protocol-required laboratory tests, as defined in Appendix 3, must be conducted in 
accordance with the Laboratory Manual and the SoA (Section 1.3). 
8.3.5. 
Pregnancy Testing 
Refer to Section 5.1 for pregnancy testing entry criteria. 
Pregnancy testing (urine or serum as required by local regulations) should be conducted as 
specified in the SoA (Section 1.3). Urine pregnancy testing will be done by dipstick at the site. 
At Screening, clinical sites will also do a serum pregnancy that will be sent to the central lab. At 
all other visits, a serum pregnancy can be conducted as needed (ie, if the site obtains a positive 
urine pregnancy test). 
Pregnancy testing (urine or serum as required by local regulations) should be conducted at the 
end of relevant systemic exposure. 
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during participation in the study. 
8.3.6. 
Suicidal Ideation and Behavior Risk Monitoring 
Participants being treated with JZP150 should be monitored appropriately and observed closely 
for suicidal ideation and behavior or any other unusual changes in behavior, especially at the 
beginning and end of the course of intervention. Participants who experience signs of suicidal 
ideation or behavior should undergo a risk assessment. All factors contributing to suicidal 
ideation or behavior should be evaluated, and consideration should be given to discontinuation of 
the study intervention. 
When informed consent has been given, families and caregivers of participants being treated 
with JZP150 should be alerted about the need to monitor participants for the emergence of 
unusual changes in behavior, as well as the emergence of suicidal ideation and behavior and to 
report such symptoms immediately to the study investigator. 
Baseline assessment of suicidal ideation and behavior/ intervention emergent suicidal ideation 
and behavior will be monitored during JZP150-201 using the C-SSRS. At the Screening Visit, 
the Baseline/Screening Version of the C-SSRS will be administered to participants to exclude 
any individuals with active suicidal ideation or behavior. 
The Since Last Visit Version of the C-SSRS will be administered to participants at every clinic 
visit after their Screening visit, including the Baseline and Follow-up visits, as well as during 
telephone calls conducted between clinic visits. At the Screening Visit, any participant who 
reports active suicidal ideation (eg, a positive response to Question 4 or 5 on the C-SSRS) or 
behavior (eg, a positive response to any suicidal behavior question on the C-SSRS) will be 
excluded. At post-baseline visits, active suicidal ideation or behavior must be recorded as an AE 
and reported to the sponsor or designee within 24 hours of first knowledge of the event by study 
personnel. Please refer to Appendix 4 for details on reporting other reportable experiences 
(OREs). 
CONFIDENTIAL
Page 63 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8.3.7. 
Marijuana Withdrawal Checklist 
The Marijuana Withdrawal Checklist will be conducted per the SoA (Section 1.3). The checklist 
is a 22-item measure developed to assess the incidence and severity of marijuana withdrawal 
symptoms. Individuals can choose from the following responses for presence of each symptom: 
0 = Not at all; 1 = Mild; 2 = Moderate; and 3 = Severe (Budney 1999). 
8.4. 
Adverse Events (AEs), Serious Adverse Events (SAEs), and Other 
Safety Reporting 
The definitions of AEs and SAEs can be found in Appendix 4. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). The investigator and any 
qualified designees are responsible for detecting, documenting, and recording events that meet 
the definition of an AE or SAE and remain responsible for following up all AEs (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 4. 
8.4.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the start of intervention until the follow-up visit at the 
time points specified in the SoA (Section 1.3). 
All SAEs that occur after the consent form is signed but before study intervention/treatment must 
be reported by the investigator if they cause the participant to be excluded from the trial, or are 
the result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment, or a procedure. 
Medical occurrences that begin before the start of study intervention but after obtaining informed 
consent will be recorded as Medical History/Current Medical Conditions, not as AEs. 
All SAEs will be recorded and reported to the sponsor or designee immediately and within 24 
hours of first knowledge of the event by study personnel, as indicated in Appendix 4. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it being 
available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the investigator should 
promptly notify the sponsor. 
8.4.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
CONFIDENTIAL
Page 64 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8.4.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and AEs of special interest (as defined in Section 8.4.6) 
will be followed until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up (as defined in Section 7.3). Further information on follow-up procedures is 
provided in Appendix 4. 
8.4.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
Investigator safety reports will be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary.  
The Reference Safety Information for the determination of expectedness of JZP150 can be found 
in the IB. 
8.4.5. 
Pregnancy 
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until 30 days after the last 
dose of study intervention. 
If a pregnancy is reported, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor within 24 hours of learning of the female participant or female 
partner of male participant (after obtaining the necessary signed informed consent from the 
female partner) pregnancy. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
The participant/pregnant female partner will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant /pregnant 
female partner and the neonate, and the information will be forwarded to the sponsor. The 
pregnancy of a participant or a female partner of a male participant will be followed until the 
CONFIDENTIAL
Page 65 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
outcome of the pregnancy is known and, in the case of a live birth, for 6 months following the 
birth of the child. The Infant Follow-up Form should be used to report information regarding the 
status of the infant.  
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.4.4. While the 
investigator is not obligated to actively seek this information in former study 
participants/pregnant female partner, he or she may learn of an SAE through spontaneous 
reporting. 
Any female participant who becomes pregnant while participating in the study will be withdrawn 
from the study. 
8.4.6. 
Adverse Events of Special Interest 
Adverse events of special interest (AEOSI) for this study are based on observations from the 
clinical studies that have been conducted with BIA 10-2474, another FAAH inhibitor 
(Kerbrat 2016). Death and severe neurological symptoms, signs, and MRI findings were reported 
only in participants taking BIA 10-2474, and have not been reported in those participants taking 
JZP150 or other FAAH inhibitors to date. Findings from the study of BIA 10-2474 suggest the 
possibility of an off-target effect associated with BIA 10-2474 or its metabolites. As no specific 
off-targets that attribute to these AEs have been identified, caution will be taken with JZP150 
and the neurological AEs that are listed as AEOSI, including headache, dizziness, gait 
disturbance, slurred speech, blurred vision, amnesia, cerebellar syndrome, such as limb ataxia, 
gait ataxia, postural ataxia, dysarthria, and nystagmus; and altered consciousness, such as 
somnolence and coma. Prompt neurological examination and necessary tests or procedures 
should be performed as necessary based on the investigator’s clinical judgment. If associated 
signs or symptoms are identified to suggest increased intracranial pressure, stroke, intracranial 
bleed, cerebral edema, or any type of progressive central nervous system disorder, the 
investigator should provide emergency treatment and submit the ORE/AEOSI Reporting form, as 
described in Appendix 4. If the event also meets the criteria for an SAE submit the SAE form 
(rather than the ORE form) as described in Appendix 4. Participants who experience 
neurological AEs that are severe or serious and related to the study intervention as judged by the 
investigator should discontinue study intervention. 
8.4.7. 
Overdose, Medication Errors, and Misuse 
Overdose (defined as any dose administered or received that was higher than the intended dose), 
medication errors (defined as any unintentional error in the dispensing or administration of the 
study intervention), and misuse of the study intervention are considered reportable experiences. 
The method for completing and transmitting reports of these experiences are provided in 
Appendix 4.  
If any overdose, medication error, or misuse of the study intervention results in an AE, this must 
be recorded. If the AE is serious, it must also be reported as described in Appendix 4. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
CONFIDENTIAL
Page 66 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8.5. 
Pharmacokinetics 
Blood samples for measurement of plasma concentration of JZP150 and its metabolites will be 
collected at the visits noted in the Schedule of Assessments (Section 1.3). Blood samples of 
4 mL will be drawn at predose and 1 sample at 2 (± 15 minutes) hours postdose on Week 1 and 
Week 12, 5 (± 15 minutes) and 8 (± 15 minutes) hours post dose on Week 8. Week 12 post-dose 
sample should be collected after completion of the CAPS-5 assessment. Blood samples will be 
taken as directed in the Laboratory Manual. The actual collection time points will be noted in the 
CRF.   
Instructions for the collection and handling of biological samples will be provided by the 
sponsor. The actual date and time (24-hour clock time) of each sample will be recorded. Samples 
will be used to evaluate the PK of JZP150 and its metabolites, if applicable. Each plasma sample 
will be divided into 2 aliquots (1 each for primary plasma PK and a back-up). All blood samples 
for PK assessments will be collected and processed according to the PK sample preparation 
instructions provided in the Laboratory Manual. The bioanalysis will be performed by the central 
laboratory as noted in the Laboratory Manual.  
A population PK model may be used to estimate PK parameters of JZP150 and its metabolites, if 
applicable. Pharmacokinetic parameters may be reported in a separate report. The 
exposure-response analysis may be conducted and reported separately.  
Study intervention concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded.  
8.6. 
Pharmacogenomics 
A 10 mL blood sample for DNA isolation will be collected from participants who have 
consented to participate in the genetic analysis component of the study at the time points noted in 
the Schedule of Assessments (Section 1.3). Participation is optional. Participants who do not 
wish to participate in the genetic research may still participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the participant. Signed informed consent will be required to obtain a replacement sample 
unless it was included in the original consent. 
See Appendix 6 for Information regarding genetic research. Details on processes for collection 
and shipment and destruction of these samples can be found in the Investigator Trial Site Binder. 
8.7. 
Biomarkers 
Blood samples of approximately 4 mL will be collected to examine plasma AEA concentration at 
the visits noted in the Schedule of Assessments (Section 1.3). When AEA draws are taken on 
days with PK draws, a single 4 mL sample will be drawn for both PK and AEA levels. In 
addition to being collected at every PK blood sample, AEA will also be drawn at Baseline and at 
the safety follow-up. 
On the days that include PK analysis, the sample will be processed and split into 2 aliquots, one 
for JZP150 levels and one for AEA levels. At Baseline and safety follow-up, the entire sample 
(4 mL) will be processed for AEA.   
CONFIDENTIAL
Page 67 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
8.8. 
Immunogenicity Assessments 
Immunogenicity assessments will not be performed in this study. 
8.9. 
Medical Resource Utilization and Health Economics 
Medical resource utilization and health economics parameters are not evaluated in this study. 
CONFIDENTIAL
Page 68 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
The pairwise comparisons of interest are between each JZP150 dose and placebo for the primary 
efficacy and key secondary efficacy variables, resulting in up to six separate null hypotheses to 
be tested.  
The null and alternative hypotheses for the primary estimand variable are: 
H0: uJZP150 = ucontrol 
H1: uJZP150 ≠ ucontrol 
where JZP150 represents either the high or low dose, as appropriate 
Specifically, the null hypothesis states that there is no difference in the mean change in CAPS-5 
total symptom severity score from Baseline to Week 12 between the indicated JZP150 dose level 
and placebo treatment groups. The alternative hypothesis states that the mean change in CAPS-5 
is not equal between the indicated JZP150 dose level and placebo. 
The null and alternative hypotheses for each key estimand variable, (CGI-S and PGI-S), are 
defined similarly as described above for the primary efficacy estimand variable. 
9.2. 
Sample Size Determination 
Approximately 270 participants will be randomized (2:1:2) to receive placebo, 0.3 mg JZP150, 
or 4 mg JZP150. Participants will be stratified by the presence or absence of concomitant use of 
SSRIs/SNRIs.  
The sample size was determined based on ensuring at least 80% marginal power to detect a 
difference of 6 between placebo and each dose of JZP150 for the mean change in CAPS-5 total 
symptom severity score from Baseline to Week 12. The sample sizes for the estimated 70% of 
subjects completing the 12-week dosing period for each arm (placebo [n = 75], 0.3 mg JZP150 
[n = 38], and 4 mg JZP150 [n = 75]) provides a marginal power of 80.9% and 93.4% for 
comparing the low dose vs placebo and high dose vs placebo, respectively. Calculations are 
based on assuming a common standard deviation of 10.5, using a two-sample t-test, and two-
sided significance level of 0.05. To account for a 30% dropout, the sample size will be 270 
participants to ensure that a minimum of 188 participants have 12 weeks of treatment data. 
9.3. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Participant Analysis Set 
Description 
Enrolled Analysis Set 
The Enrolled Analysis Set will include all participants who provide 
informed consent for this study. 
This analysis set will be used to summarize participant disposition, 
including number of screened, screen failures, and randomized 
participants. Summaries will be presented overall and by the 
randomization group for those randomized. 
CONFIDENTIAL
Page 69 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Participant Analysis Set 
Description 
Safety Analysis Set 
The Safety Analysis Set will include all participants who took at least 
one dose of study medication. Participants will be analyzed according 
to the treatment received rather than randomized. If a participant 
receives more than one randomized treatment, they will be analyzed 
according to the treatment they received the most. 
Full Analysis Set (FAS) 
The FAS will include all participants who are randomized and took at 
least one dose of study medication. Participants are analyzed according 
to randomized treatment. 
Modified FAS 
The mFAS population will include all participants who are 
randomized, took at least one dose of study medication, and have 
baseline and any post- baseline assessment of CAPS-5 total score, 
CGI-S, or PGI-S score, excluding ineligible participants that were 
randomized. Participants are analyzed according to randomized 
treatment. The mFAS analysis set will be the primary analysis set for 
all efficacy analyses. 
PK Analysis Set 
The PK Analysis Set will include all participants who receive at least 
1 dose of study intervention and have at least 1 pre-dose or 1 post-dose 
evaluable PK concentration. All PK analyses will be based on the PK 
analysis set. 
PD Analysis Set 
The PD Analysis Set will include all participants who receive at least 
1 dose of study intervention and have at least 1 pre-dose and 1 post-
dose evaluable PD (AEA) level. The PD set will be used to summarize 
the PD data. 
9.4. 
Statistical Analyses 
The statistical analysis plan (SAP) will be finalized prior to database lock and it will include a 
more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses of the most important endpoints, 
including primary and key secondary endpoints. 
9.4.1. 
General Considerations 
In general, results will be summarized by treatment group. Categorical variables will be reported 
as frequency and percent. Continuous variables will be reported as the number of participants, 
mean, SD, or SE, median, minimum, and maximum. All summaries, statistical analyses, and 
individual participant data listings described below will be completed using Version 9.3 or later 
of the SAS Statistical Analysis System (SAS Institute, Inc. Cary, NC). 
9.4.1.1. 
Multiplicity Adjustments 
A fixed sequence hierarchical testing strategy will be implemented for the primary and key 
secondary endpoints (as illustrated in Table 5) to preserve the family-wise Type 1 error rate at 
the significance level of 0.05. Testing will begin with the comparison of the JZP150 4 mg dose 
vs Placebo for the primary efficacy variable followed by sequential testing of the key secondary 
efficacy variables in the order of CGI-S and then PGI-S. If all three null hypotheses are rejected, 
CONFIDENTIAL
Page 70 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
then similar hierarchical sequential testing of the endpoints will be performed for comparing 
JZP150 0.3 mg dose vs placebo. The testing will stop when the p-value exceeds the significance 
level of 0.05. All tests will be conducted at a 2-sided significance level of 0.05. 
Table 5: 
Hierarchical Testing Strategy 
Gatekeeper 
Family 
Endpoint 
Null Hypothesis 
Effect Size 
Power 
1 
CAPS-5 
H1: JZP150 4 mg = Placebo 
0.57 
93.4% 
2 
CGI-S 
H2: JZP150 4 mg = Placebo 
0.50 
86% 
3 
PGI-S 
H3: JZP150 4 mg = Placebo 
0.50 
86% 
4 
CAPS-5 
H4: JZP150 0.3 mg = Placebo 
0.57 
80.9% 
5 
CGI-S 
H5: JZP150 0.3 mg = Placebo 
0.50 
70% 
6 
PGI-S 
H6: JZP150 0.3 mg = Placebo 
0.50 
70% 
9.4.1.2. 
Intercurrent Event Strategies  
The ICE of treatment discontinuation will be handled using two different strategies as defined 
below: 
• The treatment policy strategy will be used to address the ICE of treatment 
discontinuation. It is defined as the effect of the randomized treatment over the study 
period regardless of whether randomized treatment is continued.  
• The supplemental estimand of interest will address the ICE of treatment 
discontinuation using the hypothetical approach. This estimand is defined as the 
pharmacologic effect of JZP150 compared to placebo assuming continuation of 
randomized treatments for the duration of the study. Analysis of this estimand will be 
conducted using only data collected at time points that are obtained at or prior to 
participants discontinuing from randomized treatment will be utilized.  
Other possible ICEs include: study intervention non-compliance, significant protocol deviations, 
new trauma, or initiation or adjustment of concomitant medications for PTSD, which are not 
permitted per protocol, but nevertheless can still occur. It is anticipated that the occurrence of 
these events will be rare; therefore, both estimands use the treatment policy approach to address 
these ICEs. 
9.4.1.3. 
Pooling of Investigational Centers 
Data from all investigational centers will be pooled for presentation of the main results (eg, 
demographics, safety, PK, and efficacy). 
9.4.1.4. 
Dropouts and Missing Data 
Every effort will be undertaken to limit premature discontinuation and ascertain completeness of 
the data collection. The main estimator for the primary and key secondary estimands is based on 
a mixed effect model with repeated measures (MMRM) which can handle missing outcomes and 
produces an estimate of the treatment effect via restricted maximum likelihood estimation. For 
CONFIDENTIAL
Page 71 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
the main estimator of the estimands, the data are assumed to be missing at random (MAR). This 
assumes that participants with missing data would have efficacy outcomes similar to those 
participants in their treatment group, randomization strata, and initial trajectory who completed 
the trial.  
In order to evaluate the robustness of the primary and key secondary variables, sensitivity 
analyses will be performed for both estimands to estimate the overall treatment effect under an 
alternative assumption of missing data - missing not at random (MNAR). 
Sensitivity analyses that are planned include: 
•
Time-dependent Multiple Imputation
•
A two-dimensional tipping point analysis to study the sensitivity of the study
conclusion affected by missing data
Details of analyses will be included in the SAP. 
9.4.2. 
Primary Estimand 
Refer to Section 3 for the primary estimand attributes. 
The CAPS-5 total symptom severity score is derived by summing scores for items 1-20. Each 
item is rated with a single severity score on a five-point rating scale (0-4) corresponding to the 
following categories: 0 Absent, 1 Mild/ subthreshold, 2 Moderate/ threshold, 3 Severe/ markedly 
elevated, and 4 Extreme/ incapacitating. The CAPS-5 total symptom severity score can range 
from 0 to 80.   
A MMRM will be used to analyze the primary efficacy variable, change in CAPS-5 total 
symptom severity score from baseline at each time point. The model will include treatment 
group, week (as a discrete factor), baseline-by-week, treatment-by-week interaction, 
randomization stratum, stratum-by-week interaction, and the CAPS-5 total symptom severity 
score at baseline as fixed effects. An unstructured variance-covariance matrix will be used to 
model the correlation among repeated measurements.  
For participants meeting criteria for the mFAS population who prematurely discontinue the study 
and refuse to return for the Week 12 visit, but who do return to the study site at the time of 
discontinuation to complete the protocol-specified assessments (the early discontinuation visit), 
the efficacy data from this early discontinuation visit will be included in the primary analysis 
using the prespecified visit windows (± 4 weeks) around Week 4, and Week 12 visits. 
Refer to Section 9.4.1.2 and Section 9.4.1.4 for further details on the ICE strategies and missing 
data, respectively. 
9.4.3. 
Key Secondary Estimands 
Each key secondary efficacy estimand variable (eg, CGI-S and PGI-S) will be analyzed as a 
continuous variable using a similar method as described above for the primary efficacy variable. 
9.4.4. 
Secondary and Exploratory Estimands 
All other secondary and exploratory analyses will be further described in the SAP. 
CONFIDENTIAL
Page 72 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
9.4.5. 
Safety Analyses 
All safety analyses will be made on the Safety Population. All safety analyses will be 
descriptive; no formal statistical testing will be performed and are further described in the SAP.  
Adverse Event Analyses: 
Adverse events will be mapped to system organ classes (SOC) and preferred terms using the 
Medical Dictionary for Regulatory Activities (MedDRA). The participant incidence of AEs, AEs 
related to study intervention, SAEs, AEs leading to discontinuation, and fatal AEs will be 
summarized. This overall summary will also provide AEs by maximum severity. 
The participant incidence of AEs, AEs related to study intervention, AEs, and AEs leading to 
discontinuation will also be presented by SOC and preferred term (PT). Preferred term 
summaries may also be provided. 
The participant incidence of an AE will be summarized; if a participant has multiple events with 
the same PT occurring in different periods, the event will be reported for each of those periods. If 
an AE continues from one period to the next without increase in severity, the event will be 
reported only for the period of the AE onset. Changes in the severity of an AE within a period 
will only be counted as one AE with the worst severity. 
Vital Signs: 
For each vital sign parameter, summary statistics will be provided for observed and change from 
baseline values by scheduled visit. 
Physical Examinations: 
Observed and change from baseline values for weight will be summarized descriptively by 
scheduled visit.
 
12-lead ECG: 
Observed and change from baseline values for ECG intervals will be summarized descriptively. 
The number and percent of participants with values or change from baseline values in QT/QTcF 
exceeding certain thresholds will be tabulated. 
Clinical Laboratory Evaluations: 
Observed and change from baseline laboratory evaluations will be summarized descriptively. 
C-SSRS: 
Columbia Suicide Severity Ratio Scale parameters will be summarized by scheduled visit. 
Marijuana Withdrawal Checklist 
Marijuana Withdrawal Checklist parameters will be summarized by scheduled visit. 
9.4.6. 
Other Analyses 
Subgroup analyses for the efficacy and safety assessments will be provided by baseline presence 
or absence of concomitant use of SSRIs/SNRIs. Subgroup analyses by gender or other 
CONFIDENTIAL
Page 73 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
characteristics as defined in the SAP will be provided for efficacy and safety assessments as 
appropriate. 
9.4.7. 
Pharmacokinetic/ Pharmacodynamic Analyses 
Plasma concentrations of JZP150 and its metabolites will be listed by visit and dose. 
Pharmacodynamic markers (eg, AEA concentration) will be measured and listed by visit and 
dose.  
The results of the population PK and population PK/PD analysis may be presented separately 
from the study data. 
9.5. 
Interim Analysis 
An interim analysis is not planned. 
CONFIDENTIAL
Page 74 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− Applicable ICH Good Clinical Practice (GCP) Guidelines 
− Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC and national regulatory authority (as applicable), before 
the study is initiated. 
• Any amendments to the protocol will require IRB/IEC and national regulatory 
authority (where required) approval before implementation of changes made to the 
study design, except for changes necessary to eliminate an immediate hazard to study 
participants.  
• Protocols and any substantial amendments to the protocol will require IRB/IEC and 
national regulatory authority approval prior to initiation, except for changes necessary 
to eliminate an immediate hazard to study participants. 
• The investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), 
European Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations. 
 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
CONFIDENTIAL
Page 75 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study to the participant 
and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
If participants will be asked to consent to optional exploratory research using the remainder of 
mandatory samples, include text that addresses the use of remaining mandatory samples for 
optional exploratory research. 
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for 
 research. The investigator or authorized designee will explain to each 
participant the objectives of the 
 research. Participants will be told that they are free 
to refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a participant’s agreement to 
allow any remaining specimens to be used for 
 research. Participants who decline to 
participate in this optional research will not provide this separate signature. 
10.1.4. 
Data Protection 
Participants will be assigned a unique identifier by the sponsor. Any participant records or 
datasets that are transferred to the sponsor will contain the identifier only; participant names or 
any information that would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
CONFIDENTIAL
Page 76 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
10.1.5. 
Committees Structure 
Internal Safety Data Review Committee 
Participant safety will be continuously monitored by the sponsor’s internal safety data review 
committee (ISDRC) in a blinded manner, which includes safety signal detection at any time 
during the study. 
This committee will be composed of the following members: 
• Safety Physician 
• Clinical Safety Scientist 
• Biostatistics Lead 
• Sponsor Medical Monitor 
• Clinical Research Organization Medical Monitor 
Blinded safety data from the study will be reviewed on an ongoing basis as part of routine safety 
data review with regular review of aggregate blinded safety information within monthly JZP150 
ISDRC meetings. The ongoing review of safety data will include the following elements: 
• Abnormal, clinically significant changes in the physical examination 
 
, will be recorded as TEAEs and 
reviewed. 
• Changes from Baseline in vital signs. 
• Clinical laboratory tests (chemistry, complete blood count, urinalysi
 
 
. 
• ECG data, to include an evaluation of clinically relevant changes from Baseline. 
• TEAEs with attention to the development and frequency of previously unidentified 
TEAEs as well as identified TEAEs and the following AEOSIs: 
− Severe neurological events 
− Psychiatric events (eg, behavioral/cognitive changes, suicidal ideation or 
behavior) 
− Vision changes (eg, blurred vision) 
− Hepatic-related events (new right upper quadrant pain, hepatomegaly, tenderness, 
jaundice, serum chemistry abnormalities) 
− 
 
All blinded safety data collected will be summarized and reviewed by ISDRC for agreement of 
next steps. 
If adverse safety trends are detected that may constitute a risk to study participants prior to the 
monthly ISDRC meetings, an ad hoc Safety Management Team (SMT) meeting will be urgently 
CONFIDENTIAL
Page 77 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
convened to evaluate the information and determine actions that should be undertaken up to and 
including termination of the clinical study (Section 10.1.9.2). 
Case unblinding may be performed for above reviews if necessary, including but not limited to 
participants meeting protocol participant stopping criteria (see Section 7). The SMT will include 
membership distinct and separate from the blinded study team and its structure and standard 
operating procedures will be specified in a charter in accordance with Jazz Pharmacovigilance 
policies. 
10.1.6. 
Dissemination of Clinical Study Data 
As the sponsor of the study, Jazz Pharmaceuticals is solely responsible for disclosing results on 
ClinicalTrials.gov, EudraCT, and other public registries in accordance with applicable global 
laws and regulations. By signing this protocol, the investigator acknowledges that all posting 
requirements are solely the responsibility of the sponsor and agrees not to submit any 
information about the study or its results. 
10.1.7. 
Data Quality Assurance 
Investigators and site staff will be trained on protocol procedures and electronic case report form 
(eCRF) completion prior to enrolling participants in the study. 
All participant data relating to the study will be recorded on printed or eCRF unless transmitted 
to the sponsor or designee electronically (eg, laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
CRF. 
Guidance on completion of CRFs will be provided in data handling and entry guidelines. 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality such as 
Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues, and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the Monitoring Plan. 
The sponsor or designee is responsible for the data management of this study, including quality 
checking of the data. 
The sponsor assumes accountability for actions delegated to other individuals (eg, Contract 
Research Organizations). 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator or institution/site as applicable, for the period of time established in 
the clinical study agreement entered into by the investigator’s study site unless local regulations 
or institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor. 
CONFIDENTIAL
Page 78 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
10.1.8. 
Source Documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
Definition of what constitutes source data can be found in data handling and entry guidelines. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
10.1.9. 
Study and Site Start and Closure 
10.1.9.1. First Act of Recruitment 
The study start date is the date on which the first participant has the first visit. 
10.1.9.2. Study/Site Termination 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study site closure visit has been performed. 
Administration of the study agent will be temporarily suspended by the SMT upon the 
occurrence of any of the following:  
• Unexpected SAEs within the same SOC or similar in nature are reported by 2 or more 
participants on active study intervention with a plausible relationship to study 
intervention administration. 
• 1 or more participants on active study intervention meets Hy’s Law Criteria as 
defined in Appendix 7. 
Based on the sponsor review and evaluation of the aforementioned safety events, the study may 
be restarted or terminated. 
The investigator may initiate study site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
CONFIDENTIAL
Page 79 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
For study termination: 
• Sponsor makes a business decision to stop the study. 
• Study stopping criteria are met and following investigation, the sponsor decides to 
stop the study. 
• Ongoing evaluation of study safety data suggests that the benefit-risk profile suggests 
stopping the study. 
For site termination: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
• Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy 
Please refer to individual site contracts for specific contractual obligations and requirements. 
All information concerning JZP150, Jazz Pharmaceuticals’ operations, patent applications, 
formulas, manufacturing processes, basic scientific data, and formulation information supplied 
by Jazz Pharmaceuticals to the investigator and not previously published, are considered 
confidential and remain the sole property of Jazz Pharmaceuticals. eCRFs also remain the 
property of Jazz Pharmaceuticals. The investigator agrees to use this information only to 
complete this study and will not use it for other purposes without written consent of Jazz 
Pharmaceuticals as further detailed in the Clinical Study Agreement signed by the investigator 
and/or institution. 
It is understood by the investigator that Jazz Pharmaceuticals will use the information obtained in 
this clinical trial in connection with the study of JZP150, and therefore may disclose this 
information as required to other Jazz Pharmaceuticals investigators; appropriate international 
regulatory agencies; or others. In agreeing to participate in this study, the investigator 
understands that he/she has an obligation to provide complete test results and all data developed 
during this trial to Jazz Pharmaceuticals. Jazz Pharmaceuticals requires that permission to 
publish details of this study must be obtained in writing as further detailed in the Clinical Study 
Agreement signed by the investigator and/or institution. It is intended that the results of this trial 
will be published in scientific literature. The conditions noted here are intended to protect 
commercial confidential materials (patents, etc.) and not to restrict publication. 
 
 
CONFIDENTIAL
Page 80 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 1. ABBREVIATIONS  
Abbreviation  
Definition 
AE 
Adverse event 
AEA 
Anandamide 
AEOSI 
Adverse events of special interest 
ALT 
Alanine aminotransferase 
APA 
American Psychiatric Association 
AST 
Aspartate aminotransferase 
B-IPF 
Brief Inventory of Psychosocial Functioning 
CAPS 
Clinician Administered PTSD Scale 
CB1 
Type 1 cannabinoid receptor 
CFR 
Code of Federal Regulations 
CGI-C 
Clinical Global Impression of Change 
CGI-S 
Clinical Global Impression of Severity 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Maximum plasma concentration 
CRF 
Case report form 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CUD 
Cannabis use disorder 
CYP 
Cytochrome P450 
DoD 
Department of Defense 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
E/D 
Early Discontinuation 
FAAH 
Fatty acid amide hydrolase 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICE 
Intercurrent Events 
ICF 
Informed Consent Form 
CONFIDENTIAL
Page 81 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Abbreviation  
Definition 
ICH E6(R2) 
International Council for Harmonization Guideline for Good Clinical 
Practice 
IEC 
Independent ethics committee 
IND 
Investigational New Drug  
INR 
International normalized ratio 
IRB 
Institutional review board 
IRT 
Interactive response technology 
ISDRC 
Internal safety data review committee 
ISI 
Insomnia Severity Index 
ISTSS 
International Society for Traumatic Stress Studies 
LEC 
Life Events Checklist 
LH 
Luteinizing hormone 
mFAS 
Modified Full Analysis Set 
MINI 
Mini International Neuropsychiatric Interview 
MMRM 
Mixed Effect Model Repeated Measures 
N/A 
Not Applicable 
ng/mL 
Nanograms per Millitre 
NICE 
National Institute for Health and Care Excellence 
NOAELs 
No-observed-adverse-effect levels 
PCL-5 
PTSD Checklist 
PD 
Pharmacodynamics 
PE 
Physical examination 
PET 
Positron emission tomography 
PGI-S 
Patient Global Impression of Severity 
PHQ-9 
Patient Health Questionnaire-9 
PI 
Principal investigator 
PK 
Pharmacokinetic 
PSQI-A 
Pittsburgh Sleep Quality Index - PTSD Addendum 
PT 
Preferred term 
PTSD 
Posttraumatic stress disorder 
QD 
Once daily 
QTc 
Corrected QT interval 
QTcB 
QT interval corrected using Bazett’s formula 
QTcF 
QT interval corrected using Fridericia’s formula 
ReQoL 
Recovering Quality of Life 
CONFIDENTIAL
Page 82 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Abbreviation  
Definition 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SDS 
Sheehan Disability Scale 
SIGH-A 
Structured Interview Guide for the Hamilton Anxiety Rating Scale 
SMT 
Safety Management Team 
SNP 
Single Nucleotide Polymorphism 
SNRI 
Serotonin norepinephrine reuptake inhibitor 
SOC 
System organ class 
SSRI 
Selective serotonin reuptake inhibitor 
TEAE 
Treatment-emergent adverse event 
WOCBP 
Women of Childbearing Potential 
WONCBP 
Women of Non-childbearing Potential 
 
CONFIDENTIAL
Page 83 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 2. REFERENCES 
Ahn K, Smith SE, Limatta MB, et al. Mechanistic and pharmacological characterization of 
PF-044578845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces 
inflammatory and noninflammatory pain. Journal or Pharmacology and Experimental 
Therapeutics. 2011;338(1):114-124. 
American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental 
Disorders. 5th Edition. American Psychiatric Publishing; 2013. 
American Psychiatric Association (APA). Practice guideline for the treatment of patients with 
acute stress disorder and posttraumatic stress disorder. Arlington, VA. 2004. 
Blevins CA, Weathers FW, Davis MT, et al. The posttraumatic stress disorder checklist for 
DSM-5 (PCL-5): Development and initial psychometric evaluation. Journal of Traumatic Stress. 
2015;28(6):489-98. 
Bluett RJ, Gamble-George JC, Hermanson DJ, et al. Central anandamide deficiency predicts 
stress-induced anxiety: behavioral reversal through endo cannabinoid augmentation. 
Translational Psychiatry. 2014;4(7):e408. 
Boileau I, Rusjan PM, Williams B, et al. Blocking of fatty acid amide hydrolase activity with PF-
04457845 in human brain: a positron emission tomography study with the novel radioligand 
[11C] CURB. Journal of Cerebral Blood Flow and Metabolism. 2015;35(11):1827-35. 
Bonifacio MJ, Sousa F, Aires C, et al. Preclinical pharmacological evaluation of the fatty acid 
amide hydrolase inhibitor BIA 10-2474. British Journal of Pharmacology. 2020;177(9):2123-42. 
Bovin MJ, Marx BP, Weathers FW, et al. Psychometric properties of the PTSD Checklist for 
Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5) in veterans. 
Psychological Assessment. 2016;28(11):1379-91. 
Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for 
marijuana dependence. Addiction. 1999;94(9):1311-21. 
Burri A and Maercker A. Differences in prevalence rates of PTSD in various European countries 
explained by war exposure, other trauma and cultural value orientation. BMC Research Notes. 
2014;7(407):1-11. 
Carnevali L, Rivara S, Nalivaiko E, et al. Pharmacological inhibition of FAAH activity in 
rodents: A promising pharmacological approach for psychological-cardiac comorbidity? 
Neuroscience and Biobehavioral Reviews. 2017;74:444-52. 
Cravatt BF, Giang DK, Mayfield SP, et al. Molecular characterization of an enzyme that 
degrades neuromodulatory fatty-acid amides. Nature. 1996;384(6604):83-7. 
Dincheva I, Drysdale AT, Hartley CA, et al. FAAH genetic variation enhances fronto-amygdala 
function in mouse and human. Nature Communications. 2015;6(1):1-9. 
D'Souza DC, Cortes-Briones J, Creatura G, et al. Efficacy and safety of a fatty acid amide 
hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in 
med: a double-blind, placebo-controlled, parallel-group, phase 2a single-site randomized 
controlled trial. The Lancet Psychiatry. 2019;6(1):35-45. 
CONFIDENTIAL
Page 84 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Goldstein RB, Smith SM, Chou SP, et al. The epidemiology of DSM-5 posttraumatic stress 
disorder in the United States: results from the National epidemiologic Survey on Alcohol and 
Related Conditions-III. Social Psychiatry and Psychiatric Epidemiology. 2016;51(8):1137-48. 
Gray MJ, Litz BT. Hsu JL, et al. Psychometric properties of the Life Events Checklist. 
Assessment. 2004;11(4):330-41. 
Gunduz-Cinar O, MacPherson KP, Cinar R, et al. Convergent translational evidence of a role for 
anandamid in amygdala-mediated fear extinction, threat processing and stress-reactivity. 
Molecular Psychiatry. 2013;18(7):813-23. 
Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. 1976. Rockville, MD, US 
Department of Health, Education, and Welfare. 
Haller J, Aliczki M, Pelczer KG, et al. Effects of the fatty acid amide hydrolase inhibitor 
URB597 on coping behavior under challenging conditions in mice. Psychopharmacology. 
2014;231(3):593-601. 
Haller J, Barna I, Barsvari B, et al. Interactions between environmental aversiveness and the 
anxiolytic effects of enhanced cannabinoid signaling by FAAH inhibition in rates. 
Psychopharmacology. 2009;204(4):607-16. 
Hamilton M. The assessment of anxiety states by rating. British Journal of Medical Psychology. 
1959;31:50-5. 
Harfmann EJ, McAuliffe TL, Larson ER, et al. Circulating endocannabinoid concentrations in 
grieving adults. Psychoneuroendocrinology. 2020;120:104801. 
Hauer D, Schelling G, Gola H, et al. Plasma concentrations of endocannabinoids and related 
primary fatty acid amides in patients with posttraumatic stress disorder. PLos One. 
2013;8(5):e62741. 
Hill MN, Bierer LM, Makotkine I, et al. Reductions in circulating endocannabinoid levels in 
individuals with post-traumatic stress disorder following exposure to the World Trade Center 
attacks. Psychoneuroendocrinology. 2013a;38(12):2952-61. 
Hill MN, Campolongo P, Yehuda R, et al. Integrating endocannabinoid signaling and 
cannabinoids into the biology and treatment of posttraumatic stress disorder. 
Neuropsychopharmacology. 2018;43(1):80-102. 
Hill MN, Miller GE, Carrier EJ, et al. Circulating endocannabinoids and N-acyl ethanolamines 
are differentially regulated in major depression and following exposure to social stress. 
Psychoneuroendocrinology. 2009a;34(8):1257-62. 
Hoffman V, Middleton JC, Feltner C, et al. Psychological and Pharmacological Treatments for 
Adults with Posttraumatic Stress Disorder: A Systematic Review Update Comparative 
Effectiveness Review No. 207. (Prepared by the RTI International -University of North Carolina 
at Chapel Hill Evidence-based Practice Center under Contract No. 290-2015-00011-1 for AHRQ 
and PCORI.) AHRQ Publication No. 18-EHC011-EF. PCORI Publication No. 2018-SR-01. 
Rockville, MD. Agency for Healthcare Research and Quality; May 2018. 
CONFIDENTIAL
Page 85 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Insana SP, Hall, M, Buysse DJ, et al. Validation of the Pittsburgh Sleep Quality Index 
Addendum for posttraumatic stress disorder (PSQI-A) in male military veterans. Journal of 
Traumatic Stress. 2013;26(2):192-200. 
International Society for Traumatic Stress Studies (ISTSS) Guidelines Committee. Posttraumatic 
stress disorder prevention and treatment guidelines methodology and recommendations. 2018. 
Johnson DS, Stiff C, Lazerwith SE, et al. Discovery of PF-04457845: a highly potent, orally 
bioavailable, and selective urea FAAH inhibitor. ACS Medicinal Chemistry Letters. 
2011;2(2):91-6. 
Kathuria S, Gaetani S, Fegley D, et al. Modulation of anxiety through blockage of anandamide 
hydrolysis. Nature Medicine. 2003;9(1):76-81. 
Keetharuth AD, Brazier J, Connell J, et al. Recovering Quality of Life (ReQoL): a new generic 
self-reported outcome measure for use with people experiencing mental health difficulties. The 
British Journal of Psychiatry. 2018;212:42-9.  
Kerbrat A, Ferré J-C, Fillatre P, et al. Acute neurologic disorder from an inhibitor of fatty acid 
amide hydrolase. New England Journal of Medicine. 2016;375(18):1717-25. 
Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. Trauma and PTSD in the WHO world mental 
health surveys. European Journal of Psychotraumatology. 2017;8(sup5):1353-83. 
Kleiman SE, Bovin MJ, Black SK, et al. Psychometric properties of a brief measure of 
posttraumatic stress disorder-related impairment: The Brief Inventory of Psychosocial 
Functioning. Psychological Services. 2020;17(2):187-194. 
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity 
measure. Journal of General Internal Medicine. 2001;16:606-13. 
Krystal JH, Davis LL, Neylan TC, et al. It is time to address the crisis in the pharmacotherapy of 
posttraumatic stress disorder: a consensus statement of the PTSD psychopharmacology working 
group. Biological Psychiatry. 2017;82(7):e51-9. 
Leon AC, Olfson M, Portera L, et al. Assessing psychiatric impairment in primary care with the 
Sheehan Disability Scale. International Journal of Psychiatry in Medicine. 1997;27(2):92-105. 
Lomazzo E, Bindila L, Remmers F, et al. Therapeutic potential of inhibitors of endocannabinoid 
degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. 
Neuropsychopharmacology. 2015;40(2):488-501. 
Mayo LM, Asratian A, Linde J, et al. Elevated anandamide, enhanced recall of fear extinction, 
and attenuated stress responses following inhibition of fatty acid amide hydrolase: a randomized, 
controlled, experimental medicine trial. Biological Psychiatry. 2020;87(6):538-47. 
Morin CM, Belleville G, Belanger L, et al. The Insomnia Severity Index: Psychometric 
indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011;34(5):601-8. 
National Institute for Health and Care Excellence (NICE). Posttraumatic stress disorder. 05 
December 2018. Accesses 25 January 2021. www.nice.org.uk/guidance/ng116. 
CONFIDENTIAL
Page 86 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Patel S and Hillard CJ. Pharmacological evaluation of cannabinoid receptor ligands in a mouse 
model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. 
Journal of Pharmacology and Experimental Therapeutics. 2006;318(1):304-11. 
Rusjan PM, Knezevic D, Bioleau I, et al. Voxel level quantification of [11C] CURB, a 
radioligand for fatty acid amide hydrolase, using high resolution positron emission tomography. 
PloS One. 2018;13(2):e0192410. 
Sheehan DV, Lecrubier Y, Harnett Sheehan K, et al. The Mini-International Neuropsychiatric 
Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric 
interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry. 1998;59(suppl 20):22-33.   
Suliman S, Anthonissen L, Carr J, et al. Posttraumatic stress disorder, overweight, and obesity: a 
systematic review and meta-analysis. Harvard Review of Psychiatry. 2016 Jul 1;24(4):271-93. 
Veterans Affairs (VA) and the Department of Defense (DoD). Clinical Practice Guideline 
Working Group. Management of posttraumatic stress. Washington, DC. VA Office of Quality 
and Performance. 2003. 
Watson P. PTSD as a public health priority. Current Psychiatry Reports. 2019;21(7):1-2. 
Weathers FW, Bovin MJ, Lee DJ, et al. The Clinician Administered PTSD Scale for DSM-5 
(CAPS-5): Development and initial psychometric evaluation in military veterans. Psychological 
Assessment. 2018;30(3):383. 
Weathers FW, Litz BT, Keane TM, et al. The PTSD Checklist for DSM-5 (PCL-5). 2013. 
Available at www.ptsd.va.gov. 
CONFIDENTIAL
Page 87 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 3. CLINICAL LABORATORY TESTS 
The tests detailed in Table 6 will be performed by the central laboratory, with the exception of 
urine pregnancy, urine dipstick for drug screen (with the exception of the screening visit during 
which urine drug screen will be done by the central lab), and breath alcohol tests, which will be 
performed locally. 
Participants are required to fast for safety laboratory tests at the Baseline Visit (Visit 2), Week 1 
(Visit 3), Week 4 (Visit 5), Week 12 (Visit 9), Early Discontinuation (Visit 10), if applicable, 
and Safety Follow‑up Visit (Visit 12). Participants are not required to fast for laboratory tests at 
the Screening Visit or Week 8 (Visit 7). 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study intervention administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
intervention decision or response evaluation, the results must be recorded. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in Section 5 
of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations. 
Investigators must document their review of each laboratory report. 
Table 6: 
Protocol-Required Safety Laboratory Tests 
Laboratory Tests 
Parameters 
Hematologya 
Platelet Count  
RBC Indices: 
MCV 
MCH 
Reticulocytes (count, 
absolute) 
WBC count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical  
Chemistryab 
Albumin 
ALPc 
ALT/ SGPT 
AST/ SGOT 
BUN 
Calcium 
CO2 
Chloride 
Creatinine 
Creatine kinase GGT 
Glucose 
HbA1c 
(Screening and 
Week 12 only) 
Lactate dehydrogenase 
Phosphorus 
Potassium 
Sodium 
TSH  
(Screening only) 
Total and 
direct bilirubin 
Total 
cholesterol 
Total protein 
CONFIDENTIAL
Page 88 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
CONFIDENTIAL 
 
Laboratory Tests 
Parameters 
Triglycerides 
Uric acid 
High-density 
lipoprotein 
cholesterol 
Low-density 
lipoprotein 
cholesterol 
LH (males only) 
FSH (collected 
at Screening 
only for 
WONCBP 
when needed; 
collected at 
 
 
 
 
 
) 
Serum 
testosterone 
(males only) 
Routine Urinalysis 
•
Appearance, color
•
Specific gravity
•
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite,
leukocyte esterase (by dipstick)
•
Microscopic examination (if blood or protein is abnormal)
•
Urinalysis will always be conducted by the central laboratory.
Pregnancy testing 
•
Highly sensitive serum or urine hCG pregnancy test (as needed for
WOCBP)d
Other Screening 
Tests 
•
Follicle-stimulating hormone and estradiol (as needed for WONCBP)
•
Urine drug screen (to include at minimum: amphetamines, barbiturates,
cocaine, opiates, cannabinoids and benzodiazepines). Note: The urine drug
screen will be conducted by the central laboratory at Screening and the
urine drug screen at subsequent visits after screening will be conducted
locally at the site. In the case of a positive urine drug screen at the site,
samples can be sent to the central laboratory for confirmation.
•
Breath alcohol test
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
BUN = blood urea nitrogen; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl transferase; HbA1c = 
glycosylated hemoglobin; hCG = human chorionic gonadotropin; LH = luteinizing hormone; MCH = mean 
corpuscular hemoglobin; MCV = mean corpuscular volume; MDMA = 3, 4,-methylenedioxymethamphetamine; 
RBC = red blood cell; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic 
transaminase; TSH = thyroid stimulating hormone; WBC = white blood cell; WOCBP = woman of childbearing 
potential; WONCBP = woman of non-childbearing potential. 
CONFIDENTIAL
Page 89 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
a Participants are required to fast for safety laboratory tests at the Baseline Visit (Visit 2), Week 1 (Visit 3), Week 4 
(Visit 5), Week 12 (Visit 9), Early Discontinuation (Visit 10), if applicable, and Safety follow‑up Visit (Visit 12). 
Participants are not required to fast for laboratory tests at the Screening Visit or Week 8 (Visit 7). 
b All events of ALT (or AST) ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN (> 35% direct 
bilirubin) or ALT (or AST) ≥ 3 × ULN and international normalized ratio (INR) >1.5, (if INR measured) which 
may indicate severe liver injury (possible Hy’s Law), must be reported to the sponsor or designee in an expedited 
manner. 
c If alkaline phosphatase is elevated, consider fractionating. 
d Urine pregnancy testing will be done by dipstick at the site. At Screening, clinical sites will also do a serum 
pregnancy that will be sent to the central lab. At all other visits, a serum pregnancy can be conducted as needed 
(ie, if the site obtains a positive urine pregnancy test). 
 
CONFIDENTIAL
Page 90 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 4. ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, temporally associated 
with the use of study intervention, whether or not considered related to the study intervention. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of study intervention. 
Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, and 
Reporting 
Definition of Unsolicited and Solicited AE 
• 
An unsolicited AE is an AE that was not solicited using a Participant Diary and that is 
communicated by a participant who has signed the informed consent. Unsolicited AEs include 
serious and non-serious AEs. 
• 
Potential unsolicited AEs may be medically attended (ie, symptoms or illnesses requiring a 
hospitalization, or emergency room visit, or visit to/by a health care provider). The participants 
will be instructed to contact the site as soon as possible to report medically attended event(s), as 
well as any events that, though not medically attended, are of participant concern. Detailed 
information about reported unsolicited AEs will be collected by qualified site personnel and 
documented in the participant’s records. 
• 
Unsolicited AEs that are not medically attended nor perceived as a concern by participant will be 
collected during interview with the participants and by review of available medical records at the 
next visit. 
• 
Solicited AEs are predefined local and systemic events for which the participant is specifically 
questioned, and which are noted by the participant in their diary.  
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
CONFIDENTIAL
Page 91 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Events Meeting the AE Definition 
• 
New conditions detected or diagnosed after study intervention administration even though it may 
have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be reported as 
an AE or SAE. Such instances will be captured in the efficacy assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as an AE or 
SAE if they fulfill the definition of an AE or SAE. 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments that 
are associated with the underlying disease, unless judged by the investigator to be more severe 
than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s condition. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence SAE that, at any dose: 
Results in death 
Is life-threatening 
• 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
CONFIDENTIAL
Page 92 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
An SAE is defined as any untoward medical occurrence SAE that, at any dose: 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• 
In general, hospitalization signifies that the participant has been admitted (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment that 
would not have been appropriate in the physician’s office or outpatient setting. Complications that 
occur during hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether “hospitalization” occurred 
or was necessary, the AE should be considered serious. 
• 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline 
is not considered an AE. 
Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, 
sprained ankle) that may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
Is a congenital anomaly/birth defect 
Is a suspected transmission of any infectious agent via an authorized medicinal product. 
Other situations: 
Medical or scientific judgment should be exercised by the investigator in deciding whether SAE 
reporting is appropriate in other situations, such as significant medical events that may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other outcomes listed 
in the above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment for allergic 
bronchospasm, blood dyscrasias, convulsions, or development of intervention dependency or 
intervention abuse. 
Recording and Follow-up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all documentation 
(eg, hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The investigator will then record all relevant AE/SAE information. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical records to 
the sponsor or designee in lieu of completion of the required form. 
• 
There may be instances when copies of medical records for certain cases are requested by the 
sponsor or designee. In this case, all participant identifiers, with the exception of the participant 
CONFIDENTIAL
Page 93 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
AE and SAE Recording 
number, will be redacted on the copies of the medical records before submission to the sponsor or 
designee. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
• 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:  
o Mild: asymptomatic or mild symptoms; clinical or diagnostic observations only, intervention 
not indicated. 
o Moderate: minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living (ADL). 
o Severe: severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL. An AE/SAE that is 
assessed as severe should not be confused with a SAE. Severe is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe. 
o Life-threatening: life-threatening consequences; urgent intervention indicated. 
o Fatal: death related to AE. 
* These categories are based on the National Cancer Institute Common Terminology Criteria 
for Adverse Events version 5.0 or higher. 
When the severity of an AE increases over time, the increase in the severity will be recorded as a new 
AE and the original AE will stop when the new AE starts. 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship, cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as 
well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product Information, for 
marketed products, in his/her assessment. 
CONFIDENTIAL
Page 94 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Assessment of Causality 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the sponsor or designee. However, it is very 
important that the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to the sponsor or designee. 
• 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the sponsor (or designee) to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other health 
care professionals. 
• 
New or updated information will be recorded in the originally submitted documents. 
• 
The investigator will submit any updated SAE data to the sponsor or designee within 24 hours of 
receipt of the information. 
Reporting of SAEs 
SAE Reporting to Sponsor or Designee via an Electronic Data Collection Tool 
• 
SAEs must be reported to the sponsor (or designee) using an SAE Reporting Form within 24 hours 
of first knowledge of the event by study personnel. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
The form, instructions on completion, and contact information can be found in the Investigator 
Trial Site Binder. 
• 
The SAE Reporting Form should be completed as much as possible before transmittal. 
• 
Contacts for SAE reporting can be found in the Investigator Trial Site Binder. 
Reporting of Other Reportable Experiences (OREs) and Adverse Events of Special Interest 
(AEOSI) 
• 
Other reportable experiences (OREs, including suicidal ideation, overdose, medication error or 
abuse, and elevated LFTs) and AEOSI requiring expedited reporting, as described in Section 8.4.6, 
CONFIDENTIAL
Page 95 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
must be reported to the sponsor or its designee using an ORE/AEOSI Reporting Form within 
24 hours of first knowledge of the event by study personnel.   
• 
The form, instructions on completion, and contact information can be found in the Investigator 
Trial Site Binder. 
• 
The ORE/AEOSI Reporting Form should be completed as much as possible before transmittal.  
• 
Contacts for ORE reporting can be found in the Investigator Trial Site Binder. 
 
 
CONFIDENTIAL
Page 96 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 5. CONTRACEPTIVE AND BARRIER GUIDANCE 
Definitions 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently sterile 
(see below) 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
− A high follicle-stimulating hormone (FSH) level in the postmenopausal range 
may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than one FSH measurement 
is required.  
− Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal highly effective contraception methods if they 
wish to continue their HRT during the study. Otherwise, they must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
• Permanent sterilization methods (for the purpose of this study) include: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
− For individuals with permanent infertility due to an alternate medical cause other 
than the above (eg, Mullerian agenesis, androgen insensitivity, gonadal 
dysgenesis), investigator discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview. 
• If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation 
should be considered. 
Contraception Guidance: 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of < 1% per year when used 
consistently and correctly. 
• 
Implantable progestogen-only hormone contraception associated with inhibition of ovulationc 
CONFIDENTIAL
Page 97 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner is the sole sexual 
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, an 
additional highly effective method of contraception should be used. Spermatogenesis cycle is 
approximately 90 days. 
Note: documentation of azoospermia for a male participant can come from the site personnel’s review 
of the participant’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of < 1% per year when used consistently 
and correctly. 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of 
ovulationc 
o oral 
o intravaginal 
o transdermal 
o injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
o oral 
o injectable 
• 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant. 
a Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive 
methods for those participating in clinical studies. 
b Failure rate of < 1% per year when used consistently and correctly. Typical use failure rates differ from those when 
used consistently and correctly. 
c Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with Clinical 
Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Male 
condom and female condom should not be used together due to risk of failure from friction. 
CONFIDENTIAL
Page 98 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 6. GENETICS 
Use/Analysis of DNA 
• Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact intervention absorption, 
distribution, metabolism, and excretion; mechanism of action of the intervention; 
disease etiology; and/or molecular subtype of the disease being treated. Therefore, 
where local regulations and IRB/IEC allow, a blood sample will be collected for 
DNA analysis from consenting participants. 
• DNA samples will be used for research related to JZP150 or PTSD and related 
diseases. They may also be used to develop tests/assays including diagnostic tests 
related to JZP150. Genetic research may specifically consist of the analysis of one or 
more candidate genes or the analysis of genetic markers throughout the genome or 
targeted candidate gene analysis (as appropriate). 
• 
 
 
 
 
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to JZP150 or study interventions of this class to understand 
study disease or related conditions. 
• The results of genetic analyses may be reported in the clinical study report or in a 
separate study summary. 
• The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
• The samples will be retained while research on JZP150 continues but no longer than 
15 years or other period as per local requirements. 
CONFIDENTIAL
Page 99 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
APPENDIX 7. LIVER SAFETY: SUGGESTED ACTIONS AND 
FOLLOW-UP ASSESSMENTS  
Table 7: 
Phase 2 Liver Chemistry Stopping Criteria and Follow-up Assessments 
Liver Chemistry Stopping Criteria 
ALT-absolute 
ALT ≥ 5 × ULN 
ALT Increase 
ALT ≥ 3 × ULN persists for ≥ 4 weeks 
Total 
bilirubina,b 
ALT ≥ 3 × ULN and total bilirubin ≥ 2× ULN (> 35% direct bilirubin) 
INRb 
ALT ≥ 3 × ULN and INR >1.5, if INR measured 
Cannot 
Monitor 
ALT ≥ 3 × ULN and cannot be monitored weekly for 4 weeks 
Symptomaticc 
ALT ≥ 3 × ULN associated with symptoms (new or worsening) believed to 
be related to liver injury or hypersensitivity 
Suggested Actions, Monitoring and Follow-up Assessments  
Actions 
Follow-up Assessments 
Immediately discontinue study intervention.  
Record the Liver Stopping Events as an AE, and report 
to the sponsor or designee as an ORE, as described in 
Appendix 4. 
If the Liver Stopping Event also meets the criteria for 
an SAE, record and report to the sponsor or designee as 
an SAE, as described in Appendix 4. 
Perform follow-up assessments as described in the 
Follow-Up Assessment column.  
Monitor the participant until liver chemistry test 
abnormalities resolve, stabilize, or return to baseline 
(see MONITORING). 
 
MONITORING: 
If ALT ≥ 3 × ULN AND total bilirubin ≥ 2 × ULN 
or INR > 1.5:  
Repeat liver chemistry tests (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) and 
perform liver event follow-up assessments within 
24 hours. 
Monitor participant twice weekly until liver chemistry 
test abnormalities resolve, stabilize, or return to 
baseline. 
Viral hepatitis serology.d 
Obtain INR and recheck with each liver chemistry 
assessment until the transaminases values show 
downward trend. 
Obtain blood sample for PK analysis.e 
Obtain serum creatine phosphokinase, lactate 
dehydrogenase, GGT, glutamate dehydrogenase, and 
serum albumin. 
Fractionate bilirubin, if total bilirubin ≥ 2 × ULN. 
Obtain complete blood count with differential to assess 
eosinophilia 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity as an AE. 
Record use of concomitant medications (including 
acetaminophen, herbal remedies, recreational drugs 
and other over-the-counter medications) and provide 
information via email to 
Aereporting@jazzpharma.com. 
If ALT ≥ 3 × ULN AND total bilirubin < 2 × ULN 
or INR > 1.5 obtain the following in addition to the 
assessments listed above: 
Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G or gamma 
globulins. 
CONFIDENTIAL
Page 100 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Liver Chemistry Stopping Criteria 
A specialist or hepatology consultation is 
recommended. 
If ALT ≥ 3 × ULN AND total bilirubin < 2 × ULN 
and INR ≤ 1.5: 
Repeat liver chemistry tests (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) and 
perform liver chemistry follow-up assessments within 
24 to 72 hours. 
Monitor participants weekly until liver chemistry 
abnormalities resolve, stabilize, or return to baseline. 
Permanently discontinue study intervention and 
continue participant in the study for any 
protocol-specified follow-up assessments.  
Serum acetaminophen adduct assay, when available, to 
assess potential acetaminophen contribution to liver 
injury in participants with definite or likely 
acetaminophen use in the preceding week. 
Liver imaging (ultrasound, magnetic resonance, or 
computerized tomography) and/or liver biopsy to 
evaluate liver disease. Provide liver imagine results via 
email to Aereporting@jazzpharma.com. 
Liver biopsy may be considered and discussed with 
local specialist if available: 
In participants when serology raises the possibility of 
autoimmune hepatitis. 
In participants when suspected drug-induced liver 
injury progresses or fails to resolve on withdrawal of 
study intervention. 
In participants with acute or chronic atypical 
presentation 
If liver biopsy conducted, provide liver imaging results 
via email to Aereporting@jazzpharma.com. 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT ≥ 3 × ULN and total bilirubin ≥ 2 × ULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable 
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.  
b All events of ALT ≥ 3 × ULN and total bilirubin ≥ 2 × ULN (> 35% direct bilirubin) or ALT ≥ 3 × ULN and INR 
> 1.5 may indicate severe liver injury (possible “Hy’s Law”) and must be reported to sponsor in an expedited 
manner and as an SAE if SAE criteria met. The INR stated threshold value will not apply to participants 
receiving anticoagulants.  
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).  
d Includes: Hepatitis A immunoglobulin M (IgM) antibody; hepatitis B virus surface antigen (HBsAg) and hepatitis 
B core antibody (HBcAb); hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen 
IgM antibody (or if unavailable, heterophile antibody or monospot testing); and hepatitis E IgM antibody. 
e PK sample may not be required for participants known to be receiving placebo. Record the date/time of the PK 
blood sample draw and the date/time of the last dose of study intervention prior to the blood sample draw on the 
CRF. If the date or time of the last dose is unclear, provide the participant’s best approximation. If the date/time of 
the last dose cannot be approximated OR a PK sample cannot be collected in the time period indicated above, do 
not obtain a PK sample. Instructions for sample handling and shipping are in the Investigator Trial Site Binder. 
CONFIDENTIAL
Page 101 of 102


Jazz Pharmaceuticals, Inc. 
JZP150 
JZP150-201-02 
Amendment 02 
 
 
CONFIDENTIAL 
 
Table 8: 
Phase 2 Liver Chemistry Increased Monitoring Criteria with Continued 
Study Intervention 
Liver Chemistry Increased Monitoring Criterion and Actions With Continued Study 
Intervention 
Criterion 
Actions 
ALT ≥ 3 × ULN and < 5 × ULN and 
total bilirubin < 2 × ULN or INR < 1.5, 
without symptoms believed to be related 
to liver injury or hypersensitivity, and 
who can be monitored weekly for 
4 weeks 
Notify the sponsor within 24 hours of learning of the 
abnormality to discuss participant safety.  
Participant can continue study intervention.  
Participant must return weekly for repeat liver chemistry 
tests (ALT, AST, alkaline phosphatase, total bilirubin) 
until the abnormalities resolve, stabilize or return to 
baseline.  
If at any time, the participant meets liver chemistry 
stopping criteria, proceed as described in Section 7.1. 
If, after 4 weeks of monitoring, ALT < 3 × ULN and total 
bilirubin < 2 × ULN, monitor participants twice monthly 
until liver chemistry tests resolve, stabilize, or return to 
baseline. 
 
 
 
CONFIDENTIAL
Page 102 of 102


Signature Page for JZP150-201-02 Protocol Amendment - Published (VV-CLIN-013888)
Signature Page for JZP150-201-02 Protocol Amendment - Published (VV-CLIN-013888)
Approval Task - Approval of Document
Signing Verdict/Reason: I Approved This Document
16-Nov-2022 18:05:52 GMT+0000

SAP_001.pdf: 
Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
1 
 
 
  
 
  
STATISTICAL ANALYSIS PLAN 
 
 
VERSION: 1.0 
DATE: 12-DEC-2023 
 
STUDY DRUG: 
JZP150 
PROTOCOL/STUDY NUMBER: 
JZP150-201 Amendment 2.0 Original (16-NOV-2022) 
 
STUDY TITLE: 
A Multicenter Phase 2, 12-week Double-blind, Placebo-controlled, Randomized, Parallel-group, 
Study of JZP150 for the Treatment of Posttraumatic Stress Disorder 
SPONSOR: 
Jazz Pharmaceuticals 
3170 Porter Dr, Palo Alto, CA 94304 
   
This study is being conducted in compliance with good clinical practice, including the archiving 
of essential documents.
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
2 
 
 
  
 
SIGNATURE PAGE 
 
This document has been prepared by: 
 
 
 
 
 PhD 
 
Associate Director, Biostatistics 
Jazz Pharmaceuticals 
 
Signature 
 
Date 
 
 
 
This document has been reviewed and approved by: 
 
 
 
 
 
 MSc  
 
 
Senior Director, Biostatistics 
Jazz Pharmaceuticals  
 
Signature 
 
Date 
 
 
 
 
 PhD 
 
 
 
 
Senior Director, Clinical 
Development 
Jazz Pharmaceuticals  
 
Signature 
 
Date 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0
-12-2023 | 12:40 PM PST
Dec-12-2023 | 1:42 PM PST
Dec-12-2023 | 1:45 PM PST


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
3 
 
 
  
 
TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................3 
1. 
LIST OF ABBREVIATIONS.......................................................................................6 
2. 
MODIFICATION HISTORY .......................................................................................9 
3. 
INTRODUCTION ......................................................................................................10 
4. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................11 
4.1. 
Study Objectives .........................................................................................................11 
4.1.1. 
Primary Objective .......................................................................................................11 
4.1.2. 
Key Secondary Objective ...........................................................................................11 
4.1.3. 
Secondary Objectives .................................................................................................11 
4.1.4. 
Exploratory Objectives ...............................................................................................11 
4.2. 
Study Estimands and Endpoints .................................................................................11 
4.2.1. 
Primary Estimand .......................................................................................................11 
4.2.2. 
Key Secondary Estimands ..........................................................................................12 
4.2.3. 
Other Secondary Endpoints ........................................................................................12 
4.2.4. 
Exploratory Endpoints ................................................................................................13 
5. 
STUDY DESIGN .......................................................................................................14 
5.1. 
Summary of Study Design ..........................................................................................14 
5.2. 
Study Intervention ......................................................................................................16 
5.3. 
Power and Sample Size Calculations .........................................................................17 
5.4. 
Randomization and Blinding ......................................................................................17 
5.5. 
Interim Analysis ..........................................................................................................18 
6. 
ANALYSIS SETS ......................................................................................................18 
7. 
GENERAL ASPECTS FOR STATISTICAL ANALYSIS ........................................19 
7.1. 
General Methods .........................................................................................................19 
7.2. 
Baseline and Study Day Definitions ...........................................................................20 
7.2.1. 
Baseline .......................................................................................................................20 
7.2.2. 
Study Day ...................................................................................................................20 
7.2.3. 
Analysis Windows ......................................................................................................20 
7.2.4. 
Visit and Assessment Changes Due to COVID-19 ....................................................24 
7.2.5. 
Missing and Partial Data .............................................................................................24 
7.3. 
Hypotheses Testing .....................................................................................................24 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
4 
 
 
  
 
7.4. 
Level of Significance & Multiplicity Adjustment ......................................................25 
7.5. 
Subgroups and Subgroup Analyses ............................................................................26 
7.6. 
Intercurrent Event Strategies ......................................................................................26 
7.7. 
Statistical Modifications .............................................................................................27 
8. 
STUDY POPULATION SUMMARIES ....................................................................28 
8.1. 
Enrollment ..................................................................................................................28 
8.2. 
Participant Disposition ................................................................................................28 
8.3. 
Demographic and Baseline Characteristics ................................................................29 
8.4. 
Medical History ..........................................................................................................29 
8.5. 
Prior and Concomitant Medications ...........................................................................30 
8.6. 
Protocol Deviations ....................................................................................................30 
9. 
EFFICACY .................................................................................................................31 
9.1. 
Primary Efficacy Estimand and Analysis ...................................................................31 
9.1.1. 
Primary Estimand .......................................................................................................31 
9.1.2. 
Main Analyses ............................................................................................................32 
9.1.3. 
Sensitivity Analyses ....................................................................................................33 
9.1.4. 
Subgroup Analyses .....................................................................................................38 
9.1.5. 
Supplementary Analyses ............................................................................................38 
9.2. 
Secondary Efficacy Estimands, Endpoints and Analyses ...........................................38 
9.2.1. 
Key Secondary Estimands ..........................................................................................38 
9.2.2. 
Key Secondary Estimands Main Analysis ..................................................................38 
9.2.3. 
Key Secondary Estimands Sensitivity Analyses ........................................................39 
9.2.4. 
Key Secondary Estimands Subgroup Analyses ..........................................................40 
9.2.5. 
Key Secondary Estimands Supplementary Analyses .................................................40 
9.2.6. 
Other Secondary Efficacy Endpoints and Analyses ...................................................40 
9.3. 
Exploratory Endpoints ................................................................................................45 
10. 
SAFETY .....................................................................................................................46 
10.1. 
Exposure .....................................................................................................................46 
10.1.1. 
Extent of Exposure .....................................................................................................46 
10.1.2. 
Treatment Compliance ................................................................................................46 
10.2. 
Adverse Events ...........................................................................................................46 
10.2.1. 
Adverse Events of Special Interest .............................................................................49 
10.3. 
Laboratory Assessments .............................................................................................49 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
5 
 
 
  
 
10.3.1. 
Laboratory Normal Reference Ranges .......................................................................50 
10.4. 
Vital Signs ..................................................................................................................50 
10.4.1. 
Vital Signs Markedly Abnormal Criteria ...................................................................50 
10.5. 
ECG ............................................................................................................................51 
10.5.1. 
ECG Specific Derivations ...........................................................................................52 
10.5.2. 
ECG Abnormal Criteria ..............................................................................................52 
10.6. 
Other Safety Endpoints ...............................................................................................52 
10.6.1. 
Physical Examination .................................................................................................52 
10.6.2. 
Pregnancy testing ........................................................................................................53 
10.6.3. 
Columbia-Suicide Severity Rating Scale ....................................................................53 
10.6.4. 
Marijuana Withdrawal Checklist ................................................................................53 
11. 
PHARMACOKINETIC ANALYSES ........................................................................54 
11.1. 
Pharmacokinetic Concentrations ................................................................................54 
12. 
PHARMACODYNAMIC/BIOMARKER ANALYSES............................................55 
13. 
PHARMACOGENOMIC ANALYSES .....................................................................55 
REFERENCES ..............................................................................................................................56 
APPENDIX 1: PSQI (WITH PSQI-A) GLOBAL SCORE DERIVATION .................................57 
APPENDIX 2: DATE IMPUTATION RULES ............................................................................61 
APPENDIX 3: ICON LABORATORY SERVICES (ILS) STANDARD ADULT 
PANIC VALUES........................................................................................................63 
APPENDIX 4: STUDY SPECIFIC CHANGES TO ILS STANDARD PANIC VALUES .........65 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
6 
 
 
  
 
1. 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
Adverse event 
AEA 
Anandamide 
ALQ 
Above the Limit of Quantification 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
ATC 
Anatomical therapeutic class 
AUC 
Area under the plasma concentration-time curve 
B-IPF 
Brief Inventory of Psychosocial Functioning 
BLQ 
Below the Limit of Quantification 
BMI 
Body mass index 
CAPS-5 
Clinician Administered PTSD Scale for DSM-5 
CAPS-5 Total Score 
Clinician Administered PTSD Scale total symptom severity score 
CDISC 
Clinical Data Interchange Standards Consortium 
CGI-C 
Clinical Global Impression of Change 
CGI-S 
Clinical Global Impression of Severity 
CI 
Confidence Interval 
CK 
Creatine kinase 
cm 
Centimeter 
Cmax 
Maximum plasma concentration 
CMH 
Cochran-Mantel-Haenszel 
CNR1 
Cannabinoid receptor type 1 
COVID-19 
Coronavirus disease 2019 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTMS 
Clinical Trial Management System 
CV 
Coefficient of variation 
DBP 
Diastolic blood pressure 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
eCRF 
Electronic case report form 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
7 
 
 
  
 
E/D 
Early discontinuation 
EoS 
End of study 
F 
Female 
FAAH 
Fatty acid amide hydrolase 
HCG 
Human chorionic gonadotropin 
HGB 
Hemoglobin 
HR 
Heart rate 
ICE 
Intercurrent event 
ICF 
Informed consent form 
ICH 
International Council for Harmonization 
INR 
International normalized ratio 
ILS 
ICON Laboratory Services 
IRT 
Interactive response technology 
ISI 
Insomnia Severity Index 
ITT 
Intention-to-Treat 
kg 
Kilogram 
kg/m2 
Kilogram per square meter 
LEC-5 
Life Event Checklist for DSM-5 
LLN 
Lower limit of normal 
LS 
Least square 
M 
Male 
MAR 
Missing at random 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minimum 
min 
Minute 
MINI 
Mini International Neuropsychiatric Interview 
mmHg 
Millimeter of mercury 
MMRM 
Mixed-effect model with repeated measures 
MNAR 
Missing not at random 
msec 
Millisecond 
MWC 
Marijuana withdrawal checklist 
n 
Number of participants 
PCL-5 
PTSD Checklist for DSM-5 
PD 
Pharmacodynamics  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
8 
 
 
  
 
PE  
Physical examination 
PG 
Pharmacogenomics 
PGI-S 
Patient Global Impression of Severity 
PHQ-9 
Patient Health Questionnaire-9 
PK 
Pharmacokinetics 
PSQI 
Pittsburgh Sleep Quality Index  
PSQI-A 
Pittsburgh Sleep Quality Index - PTSD Addendum 
PT 
Preferred Term 
PT 
Prothrombin time 
PTSD 
Posttraumatic Stress Disorder 
QD 
Once daily 
QTcB 
QT Bazett’s Correction 
QTcF 
QT Fridericia’s Correction  
REML 
Restricted maximum likelihood estimation 
ReQoL 
Recovering Quality of Life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SE 
Standard error 
SBP 
Systolic blood pressure 
SDS 
Sheehan Disability Scale 
SIGH-A 
Structured Interview Guide for the Hamilton Anxiety Rating Scale 
 
SNRI 
Serotonin norepinephrine reuptake inhibitor 
SOC 
System Organ Class 
SSRI 
Selective serotonin reuptake inhibitor 
t1/2 
Terminal half-life 
TEAE 
Treatment emergent adverse event 
Tmax 
Time to maximum concentration 
ULN 
Upper limit of normal 
yrs 
Years 
WBC 
White blood cell 
WHO 
World Health Organization 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
9 
 
 
  
 
2. 
MODIFICATION HISTORY 
Version History for SAP: 
Version 
Date 
Description  
Version 1.0 
12 Dec 2023 
Original 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
10 
 
 
  
 
3. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe in detail the statistical 
methodology and planned analyses to be conducted for Protocol JZP150-201-02 for inclusion in 
the Clinical Study Report (CSR). The current version is based on Protocol Amendment 02 dated 
16 November 2022. Any additional analyses or deviation from the analyses outlined in this plan 
will be documented with rationale in SAP amendments and in the final CSR. 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
11 
 
 
  
 
4. 
STUDY OBJECTIVES AND ENDPOINTS 
4.1. 
Study Objectives 
4.1.1. 
Primary Objective 
To evaluate the efficacy of JZP150 administered once daily for up to 12 weeks at doses of 
0.3 mg and 4 mg compared to placebo in the treatment of adults with posttraumatic stress 
disorder (PTSD), as measured by the change in Clinician Administered PTSD Scale for DSM-5 
(CAPS-5) total symptom severity score (CAPS-5 total score). 
4.1.2. 
Key Secondary Objective 
To evaluate the efficacy of JZP150 administered once daily for 12 weeks at doses of 0.3 mg and 
4 mg compared to placebo on overall clinician and patient impression of severity. 
4.1.3. 
Secondary Objectives 
The secondary objectives of the study are: 
 To evaluate the efficacy of JZP150 administered once daily for 12 weeks at doses of 
0.3 mg and 4 mg compared to placebo on functional outcomes and participant reported 
symptoms in adults with PTSD. 
 To evaluate the safety and tolerability of JZP150 administered once daily for up to 
12 weeks at doses of 0.3 mg and 4 mg in adults with PTSD. 
 To characterize the pharmacokinetic (PK) and pharmacodynamics (PD) of JZP150 in 
adults with PTSD using population PK modeling and simulation methodology. 
 
4.2. 
Study Estimands and Endpoints 
Study estimands and intercurrent events (ICEs) strategies are constructed based on International 
Conference on Harmonization (ICH) E9 (R1) (ICH 2021). 
4.2.1. 
Primary Estimand 
The primary estimand of the study is defined as: 
 Treatment: 0.3 mg and 4 mg of JZP150, and placebo. 
 Population: Participants with PTSD (as defined in the eligibility criteria).  
 Variable (endpoint): CAPS-5 total score change from Baseline to Week 12. 
 ICEs: The main ICE treatment discontinuation will be addressed by treatment policy 
(primary strategy) and hypothetical approach (alternative strategy). Other possible ICEs 
are defined in Section 7.6.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
12 
 
 
  
 
 Population-level summary: The mean change from Baseline to Week 12 in CAPS-5 total 
score for each randomized treatment group and the difference in means between each 
randomized treatment group compared to placebo. 
4.2.2. 
Key Secondary Estimands 
The two key secondary estimands of the study are defined as follows.  
Key Secondary Estimand 1: 
• Treatment: 0.3 mg and 4 mg of JZP150, and placebo. 
• Population: Participants with PTSD (as defined in the eligibility criteria).  
• Variable (endpoint): Change in Clinical Global Impression of Severity (CGI-S) from 
Baseline to Week 12. 
• ICEs: The main ICE treatment discontinuation will be addressed by treatment policy 
(primary strategy) and hypothetical approach (alternative strategy). Other possible ICEs are 
defined in Section 7.6.  
• Population-level summary: The mean change from Baseline to Week 12 in CGI-S for each 
randomized treatment group and the difference in means between each randomized treatment 
group compared to placebo. 
Key Secondary Estimand 2: 
• Treatment: 0.3 mg and 4 mg of JZP150, and placebo. 
• Population: Participants with PTSD (as defined in the eligibility criteria).  
• Variable (endpoint): Change in Patient Global Impression of Severity (PGI-S) from 
Baseline to Week 12. 
• ICEs: The main ICE treatment discontinuation will be addressed by treatment policy 
(primary strategy) and hypothetical approach (alternative strategy). Other possible ICEs are 
defined in Section 7.6.  
• Population-level summary: The mean change from Baseline to Week 12 in PGI-S for each 
randomized treatment group and the difference in means between each randomized treatment 
group compared to placebo. 
4.2.3. 
Other Secondary Endpoints 
Other secondary efficacy endpoints include: 
 CAPS-5 total score responder: Percent of participants with ≥ 30% improvement on the 
CAPS-5 total score from Baseline to Week 12. 
 CGI-C responder: Percent of participants who are very much or much improved on the 
CGI-C at Weeks 4 and 12. 
 PGI-S responder: Percent of participants with ≥ 1 unit of improvement on the PGI-S from 
Baseline to Week 12. 
 CAPS-5 total score change from Baseline to Week 4. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
13 
 
 
  
 
 Change in functional outcomes measured by the Brief Inventory of Psychosocial 
Functioning (B-IPF) and Sheehan Disability Scale (SDS) from Baseline to Week 12.  
 Change in patient and clinician-reported symptoms of PTSD as assessed by the PTSD 
Checklist (PCL-5) from Baseline to Weeks 1, 4, 8, and 12. 
 Change in patient and clinician-reported symptoms of PTSD as assessed by PGI-S and 
CGI-S from Baseline to Weeks 1, 4, and 8. 
 Change in self-reported sleep problems as measured by the Insomnia Severity Index (ISI) 
and Pittsburgh Sleep Quality Index (PSQI; with the PSQI-addendum [PSQI-A]) from 
Baseline to Week 12. 
 Change in PTSD symptom clusters (intrusive symptoms, avoidance symptoms, 
arousal/reactivity symptoms, and negative alterations in mood and cognition) as assessed 
by the change in the subscales of the CAPS-5 from Baseline to Weeks 4 and 12. 
 Change in mood and anxiety as assessed by the change in Patient Health Questionnaire 
(PHQ-9) from Baseline to Weeks 1, 4, 12 and the change in the Structured Interview 
Guide for the Hamilton Anxiety Scale (SIGH-A) from Baseline to Weeks 4, 8, 12.  
 Change in quality of life from Baseline to Week 12 as measured by the Recovering 
Quality of Life (ReQoL). 
The safety endpoints of this study include:  
 AEs 
 Vital signs 
 Physical examination (PE) 
 
 12-lead electrocardiogram (ECG) 
 Clinical laboratory tests (chemistry, hematology, urinalysis, 
 
) 
 Columbia Suicide Severity Rating Scale (C-SSRS) 
 Withdrawal scale (marijuana withdrawal checklist [MWC]) 
The PK/PD endpoints of this study include: 
 Plasma concentration of Anandamide (AEA), JZP150 and its metabolites. 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
14 
 
 
  
 
5. 
STUDY DESIGN 
5.1. 
Summary of Study Design 
This is a 12-week, double-blind, placebo-controlled, randomized, parallel-group, multicenter 
study of the safety and efficacy of JZP150 in the treatment of adult participants with PTSD. 
Participants who meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition 
(DSM-5) criteria for PTSD as confirmed by the Mini International Neuropsychiatric Interview 
(MINI), with a total PCL-5 score ≥ 33 at Screening and Baseline will be eligible for enrollment. 
Approximately 270 participants will be randomized (2:1:2) to receive placebo, 0.3 mg JZP150, 
or 4 mg JZP150 to ensure that a minimum of 188 participants have 12 weeks of treatment. 
Participants will be stratified by the presence or absence of concomitant use of selective 
serotonin reuptake inhibitor (SSRIs)/ serotonin norepinephrine reuptake inhibitor (SNRIs). The 
study will consist of the following periods:  
 Screening period and washout of prohibited medications (up to 28 days). 
 Baseline and randomization (Day -1). 
 Double-blind Treatment Period (12 weeks). 
 Safety follow-up (2 weeks). 
The timing and number of administrations of the CAPS-5 has been carefully considered to 
address the high placebo response rate that has been observed in previous PTSD trials with 
sertraline and paroxetine (Hodgins et al 2018). Due to the therapeutic alliance that occurs with 
the administration of the CAPS-5, and the effect this can have on an already high placebo 
response rate, our CAPS-5 administration schedule aims to minimize the number of CAPS-5 
administrations during the study and to maximize the time between administrations. For this 
reason, the CAPS-5 is conducted only at Baseline and end of Weeks 4 and 12. 
Another important design feature is that if study intervention is permanently discontinued, the 
participant will be requested to remain in the study and be asked to complete a 12-week efficacy 
follow-up to collect efficacy and safety data. Every effort will be made to have the participant 
attend an early discontinuation visit and the Week 12 efficacy follow-up. For those participants 
who discontinue study intervention prior to Week 4, every effort will be made to have the 
participant complete the efficacy follow-up at Week 4 and Week 12. The study protocol specifies 
analysis windows of +/- 4 weeks for the Week 4 and Week 12 visits.  Therefore, the protocol 
intends for efficacy data to be collected at an early discontinuation visit and efficacy follow-up 
visits, regardless of any ICE, such as early discontinuation from treatment, allowing for the 
analysis of the primary, key secondary, and other secondary estimands using the treatment 
policy.  
The schema of study is shown in Figure 1. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
15 
 
 
  
 
 
Figure 1: The schema of study 
 
Abbreviations: QD=Once daily. 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
16 
 
 
  
 
 
5.2. 
Study Intervention 
The study interventions planned for use in this study are described in Table 1 below.  
Table 1: 
Study Intervention 
Treatment 
Arm 
Intervention/Treatment 
Name 
Formulation 
Unit Dose 
Strength(s) 
Dosage 
Level(s) 
Route of 
Administration 
Use 
Sourcing 
Packaging 
Labeling 
Storage 
Conditions 
1 
Placebo 
Capsule 
Placebo 
QD 
Oral 
Placebo 
Provided 
centrally 
by the 
Sponsor 
Bottles 
with 30 
capsules/ 
bottle 
Double-
blind 
 
2 
JZP150  
Capsule 
0.3 mg 
QD 
Oral 
Experimental 
Provided 
centrally 
by the 
Sponsor 
Bottles 
with 30 
capsules/ 
bottle 
Double-
blind 
 
3 
JZP150 
Capsule 
4 mg 
QD 
Oral 
Experimental 
Provided 
centrally 
by the 
Sponsor 
Bottles 
with 30 
capsules/ 
bottle 
Double-
blind 
 
Abbreviations: mg = milligram; QD = once daily
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
17 
 
 
  
 
 
5.3. 
Power and Sample Size Calculations 
Approximately 270 participants will be randomized (2:1:2) to receive placebo, 0.3 mg JZP150, 
or 4 mg JZP150. 
The sample size was determined based on ensuring at least 80% marginal power to detect a 
difference of 6 between placebo and each dose of JZP150 for the change in CAPS-5 total score 
from Baseline to Week 12 (Stefanovics et al 2018; Stein et al 2006). The sample size for the 
estimated 70% of evaluable participants completing the 12-week dosing period for each arm 
(placebo [n = 75], 0.3 mg JZP150 [n = 38], and 4 mg JZP150 [n = 75]) provides a marginal 
power of 93.4% and 80.9% for comparing the high dose vs placebo and low dose vs placebo, 
respectively. Calculations are based on assuming a common standard deviation of 10.5, using a 
two-sample t-test, and two-sided significance level of 0.05. To account for a 30% dropout, a total 
of 270 participants will be randomized to ensure that a minimum of 188 participants have 12 
weeks of intervention data. 
5.4. 
Randomization and Blinding 
All participants who sign the informed consent form (ICF) will receive a participant number. The 
participant number identifies the participant for all study procedures that occur throughout the 
study. This number is unique and once assigned cannot be reassigned to another study 
participant.  
Treatment allocation/randomization for this study will occur centrally through the use of an 
interactive response technology (IRT). Following screening, eligible participants will be 
randomized (2:1:2) to one of three treatment arms: placebo, JZP150 0.3 mg QD, or JZP150 4 mg 
QD. Randomization will be stratified based on presence versus absence of use of a stable 
SSRI/SNRI at Screening. The sponsor, CRO, study investigators, clinical raters, and participants 
will be blinded to treatment assignment. 
A double-blind approach will be used throughout the 12-week treatment period. During the 
study, the number of capsules taken each day will be the same for participants randomized to 
each treatment, and JZP150 and placebo capsules will look and feel identical. 
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
investigator has the sole responsibility for determining if unblinding of a participant’s 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a participant’s 
intervention assignment unless this could delay emergency treatment of the participant. If a 
participant’s intervention assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason(s) that the blind was broken must be recorded in the 
source documentation and case report form, as applicable. The participant’s treatment 
assignment may be unblinded for regulatory reporting purposes. Notification of the treatment 
assignment is only made known to those who require it for safety reporting and submission 
processes. All other individuals involved in the study, including the investigator (with the 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
18 
 
 
  
 
exception noted above), will remain blinded to treatment assignment. Participants for whom the 
blind is broken for this reason will not be withdrawn from the study. 
Sponsor safety staff may unblind the intervention assignment for any participant with a serious 
adverse event (SAE) considered related to study intervention. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the report 
identifying the participant’s intervention assignment may be sent to investigators in accordance 
with local regulations and/or sponsor policy. 
 
5.5. 
Interim Analysis 
No interim analysis is planned. 
6. 
ANALYSIS SETS 
For purposes of analysis, the following populations are defined in Table 2. 
Table 2: Analysis Sets 
Analysis Set 
Description 
Enrolled Analysis Set 
The Enrolled Analysis Set includes all participants who provided 
a signed ICF. This analysis set will be used to summarize 
participant disposition including number of screened, screen 
failures, and randomized participants.  
Full Analysis Set 1 
The Full Analysis Set 1 includes all participants who were 
randomized and took at least 1 dose of the study intervention, 
excluding Site 1865*. This analysis set will be the primary 
analysis set for all efficacy analyses. This analysis set will also 
be used in the concordance analysis to examine the classification 
of participants in randomization strata according to different data 
sources. Participants will be summarized according to the 
treatment group they were randomized to.  
Full Analysis Set 2 
The Full Analysis Set 2 includes all participants who were 
randomized and took at least 1 dose of the study intervention. 
This analysis set will be used to summarize participant 
disposition and protocol deviations. This analysis set will also be 
used in supplementary efficacy analysis. Participants will be 
summarized according to the treatment group they were 
randomized to.  
Safety Analysis Set 
The Safety Analysis Set includes all participants who took at 
least 1 dose of study intervention. This analysis set will be used 
to summarize participants’ demographic and other baseline 
characteristics data, past medical conditions/diseases, surgical 
history, medications, PTSD diagnosis history, exposure to study 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
19 
 
 
  
 
Analysis Set 
Description 
intervention, as well as all safety data. Participants will be 
summarized according to the study intervention they actually 
received. 
Modified Full Analysis 
Set 
The Modified Full Analysis Set includes all participants in the 
Full Analysis Set 1 who have baseline and at least 1 post-
baseline assessment of CAPS-5 total score, CGI-S, or PGI-S 
score, excluding ineligible participants that were randomized. 
This analysis set will be used in supplementary efficacy analysis. 
Participants will be summarized according to the treatment group 
they were randomized to. 
PK Analysis Set  
The PK Analysis Set includes all participants who received at 
least 1 dose of study intervention and have at least 1 post-dose 
(post first dose) evaluable PK concentration. The PK set will be 
used to summarize the PK data, demographic and other baseline 
characteristics data, as well as exposure to study intervention.  
PD Analysis Set  
The PD Analysis Set includes all participants who received at 
least 1 dose of study intervention and have at least 1 pre-dose 
(prior to first dose) and 1 post-dose (post first dose) evaluable PD 
(AEA) level. The PD set will be used to summarize the PD data.  
* Randomized participants from Site 1865 were excluded from this analysis set due to observed serious 
deviations and significant breaches to the principles of Good Clinical Practice during the study, particularly in the 
collection of efficacy data. These deviations and breaches are suspected to be gross misconduct and thus 
considered to have compromised the integrity of the efficacy data collected and reported by this site.  
7. 
GENERAL ASPECTS FOR STATISTICAL ANALYSIS 
The statistical principles applied in the design and planned analyses of this study are consistent 
with ICH E9 guidelines (ICH 1998). 
7.1. 
General Methods 
Data will be listed and summarized according to Clinical Data Interchange Standards 
Consortium (CDISC) standards. SAS software Version 9.4 or higher (SAS Institute, Inc. Cary, 
NC) will be used to perform all data analyses, generate tables, figures, and listings. 
Categorical variables will be presented using counts and percentages. Unless otherwise specified, 
continuous data will be summarized using descriptive statistics comprising of the number of 
participants with data to be summarized (n), mean, standard deviation (SD), median, minimum 
(Min) and maximum (Max).  
For quantitative measurements, change from baseline will be calculated as: 
 Change from baseline = Test value at visit X – baseline value  
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
20 
 
 
  
 
7.2. 
Baseline and Study Day Definitions 
7.2.1. 
Baseline 
For the study assessments that are either clinician-reported or patient-reported outcomes (CAPS-
5, CGI-S, CGI-C, PGI-S, PCL-5, B-IPF, ReQoL-10, SDS, PSQI, PSQI-A, ISI, PHQ-9, SIGH-A, 
MWC, and C-SSRS), the baseline value is defined as the initial value obtained on the date of the 
Baseline Visit (Day -1). If this value is missing, the last non-missing value obtained prior to the 
first dose of study intervention will be used as the baseline value. Repeat assessments performed 
on the same Baseline Visit date will be included in the clinical database as unscheduled 
assessment but will not be utilized for analyses. If the scheduled Baseline Visit occurred on the 
same day (Day 1) of first dosing, the assessment of the above-mentioned endpoints should be 
considered prior to first dosing. 
 
For all other assessments, the last non-missing value obtained prior to the initiation of study 
intervention will be used as the baseline value.  
7.2.2. 
Study Day 
A study day will be assigned as follows: 
 The first dose of study intervention is designated as Day 1. Participants will self-
administer the first dose at home the day after the Baseline Visit.  
 For visit days after Day 1, study day = visit date - Day 1 date + 1. 
 For visit days prior to Day 1, study day = visit date - Day 1 date. Thus, study days for 
screening visit are negative numbers. There is no “Day 0”. 
 The end date of study intervention for each participant is the participant’s last dose 
date in the study. 
 The end date of the study for each participant is defined as the date of the 
participant’s last assessment, including the safety follow-up and the efficacy follow-
up (if the participant stops study intervention) in the study. 
7.2.3. 
 Analysis Windows 
All scheduled, unscheduled, and early termination assessments will be summarized by derived 
analysis visit per Table 3, regardless of if the visit was performed on-site or remotely. Visit dates 
will be mapped based on the scheduled period of each visit, with adjusted analysis-defined 
windows as specified in Table 3. 
Height, serum pregnancy, demographics, medical/surgical history, MINI, C-SSRS 
(screening/baseline version), and Life Event Checklist for DSM-5 (LEC-5) are only assessed at 
Screening Visit. The analysis window for these assessments is Day -40 up to -2.  
CGI-S, PGI-S, CGI-C, PCL-5, and C-SSRS since last visit will be assessed at efficacy and safety 
follow-up visits. CAPS-5 will be assessed at efficacy follow-up visits (if applicable) but will not 
be assessed at the safety follow-up visit. PSQI-A, PSQI, ISI, MWC, and PHQ-9 will be assessed 
at safety follow-up visit but not at efficacy follow-up visits. AEs and prior/concomitant 
medications are monitored throughout the study. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
21 
 
 
  
 
A clinic visit at the end of Week 8 is also included for safety assessments, secondary efficacy 
assessments, sparse PK sampling and study intervention dispensation. 
If multiple measurements are recorded within a single analysis window, including unscheduled 
or repeated assessments, early discontinuation assessments, as well as efficacy and safety follow-
up assessments, the following rules will be applied to determine the observation from which 
assessment will be used for that analysis defined visit.  
 
If there are two or more observations within the same analysis window, then the non-
missing observation closest to the scheduled Visit Day will be used in the analysis.  
 
If two observations are equidistant from the scheduled Visit Day, the on-treatment 
observation will prioritize over the off-treatment observation, with the exception for 
safety follow-up visit. If they are both on-treatment observations, then the non-missing 
observation with the latest collection date will be used in the analysis.  
 
If two observations are collected on the same day and this day is the closest to the 
scheduled Visit Day, for efficacy endpoints, the non-missing observation with the earliest 
collection time will be used in the analysis; for safety endpoints, the non-missing 
observation with the latest collection time will be included in the analysis.  
Data collected from safety follow-up visit between 7 to 28 days after the last dose can be mapped 
to the safety follow-up analysis visit. Safety follow-up visits that take place at > 28 days post last 
dose will be considered out of window and the data collected will not be used.  
If an analysis window does not contain any observations, then the data will remain missing for 
the analysis visit.  
Listings will include scheduled, unscheduled, repeated, retest, early termination, efficacy follow-
up and safety follow-up data per nominal visits. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
22 
 
 
  
 
Table 3: Analysis Windows for Assessments or Measurements 
Study Period 
Scheduled 
Visit (V)/ 
Week(W) 
Scheduled  
Visit Day 
CAPS-
5, 
SDSa 
 
CGI-S, 
PGI-S, 
PSQI, 
PSQI-
Ab, 
ISIb 
 
 
PCL-5 
 
 
C-SSRS 
CGI-C 
MINI, 
LEC-5, 
Height, 
Serum 
Pregnan
cy Test 
B-IPFc, 
ReQoL-
10c, 
MWC 
PHQ-9 
SIGH-
Ad, PE 
Laborato
ry, Vital 
Signs, 
ECGe,  
Breath 
Alcohol 
Teste,  
Urine 
Drug 
Screene  
Urine 
Pregnan
cy Test 
Blood 
Sample 
PKf, 
AEA, 
PGg 
 
Screening 
V1 
-40 up to -2 
na 
na 
-40 up 
to -2 
-40 up to 
-2 
na 
-40 up to 
-2 
na 
-40 up to 
-2 
-40 up 
to -2 
-40 up to -
2 
-40 up to 
-2 
na 
Baselineh/ 
Randomization 
V2 
-1 
-1 
-1 
-1 
-1 
na 
na 
-1 
-1 
-1 
-1  
-1 
-1 
Double-Blind 
Intervention   
V3/W1 
7±2 
na 
1-14 
1-14 
1-7 
na 
na 
na 
1-14 
na 
1-14 
na 
1-42 
V4/W2 (call) 
14±2 
na 
na 
na 
8-14 
na 
na 
na 
na 
na 
na 
na 
na 
V5/W4 
28±2 
1-56 
15-42 
15-42 
15-28 
1-56 
na 
na 
15-56 
1-42 
15-42 
na 
na 
V6/W6 (call) 
42±2 
na 
na 
na 
29-42 
na 
na 
na 
na 
na 
na 
na 
na 
V7/W8 
56±2 
na 
43-70 
43-70 
43-56 
na 
na 
na 
na 
43-70 
43-70 
na 
43-70 
V8/W10 (call) 
70±2 
na 
na 
na 
57-70 
na 
na 
na 
na 
na 
na 
na 
na 
V9/W12 
84 (-5, +2) 
57-112 
71-112 
71-112 
71-112 
57-112 
na 
1-112 
57-112 
71-112 
71-112 
1-112 
71-112 
Efficacy 
Follow-up 
V11a/W4  
28 
1-56 
1-56 
1-56 
1-56 
1-56 
na 
na 
na 
na 
na 
na 
na 
V11/W12  
84 
57-112 
57-112 
57-112 
57-112 
57-112 
na 
na 
na 
na 
na 
na 
Na 
Safety Follow-
up 
Safety 
Follow-up 
 
98(+5) 
na 
8-112 
8-112 
8-112 
8-112 
na 
8-112 
8-112 
na 
8-112 
8-112 
8-112 
Abbreviations. AEA = anandamide; B-IPF = Brief Inventory of Psychosocial Functioning; E/D = Early Discontinuation; CAPS-5 = 
Clinician Administered PTSD Scale version 5; CGI-C = Clinical Global Impression of Change; CGI-S = Clinical Global Impression of Severity; C-SSRS = 
Columbia Suicide Severity Rating Scale; ECG = Electrocardiogram; ISI = Insomnia Severity Index; LEC-5 = Life Events Checklist for DSM-5; MINI = Mini 
International Neuropsychiatric Interview; MWC=Marijuana withdrawal checklist; PCL-5 = Posttraumatic Checklist-5; PE=Physical examination; 
PG=Pharmacogenomics; PGI-S = Patient Global Impression of Severity; PHQ-9 = Patient Heath Questionnaire-9; PK = pharmacokinetics; PSQI =  Pittsburgh 
Sleep Quality Index – PTSD; PSQI-A = Pittsburgh Sleep Quality Index with PTSD Addendum; PTSD = posttraumatic stress disorder; ReQoL = Recovering 
Quality of Life; SDS = Sheehan Disability Scale; SIGH-A = Structured Interview Guide for the Hamilton Anxiety Rating Scale. 
a SDS is not assessed at efficacy or safety follow-up visits. 
b PSQI, PSQI-A and ISI are not assessed at efficacy follow-up visits. 
c B-IPF and ReQoL are not assessed at safety follow-up visit. 
d SIGH-A is not assessed at screening visit. 
e ECG, breath alcohol test, and urine drug screen are not assessed at safety follow-up visit. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
23 
 
 
  
 
f Blood sample for PK is not collected at baseline or safety follow-up visit. 
g Blood sample for PG is only collected at baseline visit. 
h For detailed baseline definition, refer to Section 7.2.1. 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
24 
 
 
  
 
7.2.4. 
Visit and Assessment Changes Due to COVID-19  
The investigator may opt to have the participant attend an unscheduled visit, if deemed 
necessary, at any time during the study. Some clinic visits may be shortened and/or conducted 
remotely, if required due to the COVID-19 (or other) pandemic, and with approval from the 
Sponsor’s Medical Monitor. Protocol waivers or exemptions are not allowed. 
Changes in scheduled visits and corresponding assessments due to COVID-19 (or other) 
pandemic restrictions will be reported. Submission datasets will include flags for all missing 
visits and assessments where the “not done” field is indicated and the reason for “not done” 
contains “COVID” in the description field. The protocol deviation log will also be reviewed to 
assess whether deviations are due to COVID-19. 
7.2.5. 
Missing and Partial Data 
Missing or partially missing concomitant medications and AEs start and stop dates will be 
imputed as described in Appendix 2. However, imputed dates will not be presented in the listings 
as their sole purpose will be for the classification of the medications and the AEs. 
Missing data will be handled as described in the following sections: 
 
Missing safety data will not be imputed except for AEs and concomitant medication start 
and stop dates as described above. 
 
For multi-item questionnaires such as CAPS-5, we expect few missing items in the total 
score such as the CAPS-5 total score. The electronic clinical outcome assessment 
platform adopted for this study prevents the rater from proceeding to the next item if 
there are missing items in the questionnaire.  
 
Missing data for the primary estimand and key secondary estimands will not be explicitly 
imputed for main analyses but will be imputed in sensitivity analyses. 
 
Missing data will not be imputed for other secondary endpoints, and exploratory 
endpoints. 
 
7.3. 
Hypotheses Testing 
To evaluate the efficacy of JZP150 at doses of 4 mg/day and 0.3 mg/day compared with placebo, 
pairwise comparisons between each of the doses and placebo will be conducted at the end of 
Week 12 for the primary and key secondary endpoints, resulting in up to six separate null 
hypotheses to be tested. 
The null (H0i) and alternative (HAi) hypotheses for analysis of the primary efficacy and key 
secondary efficacy variables (CAPS-5, CGI-S and PGI-S) at each of JZP150 4 mg and 0.3 mg vs 
placebo are:  
H01(CAPS-5): Δμ(JZP150, 4 mg) = Δμ(Placebo) vs  HA1(CAPS-5): Δμ(JZP150, 4 mg) ≠ Δμ(Placebo) 
H02(CGI-S): Δμ(JZP150, 4 mg) = Δμ(Placebo) vs.  HA2(CGI-S): Δμ(JZP150, 4 mg) ≠ Δμ(C Placebo) 
H03(PGI-S): Δμ(JZP150, 4 mg) = Δμ(Placebo) vs HA3(PGI-S): Δμ(JZP150, 4 mg) ≠ Δμ(Placebo) 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
25 
 
 
  
 
H04(CAPS-5): Δμ(JZP150, 0.3 mg) = Δμ(Placebo) vs HA4(CAPS-5): Δμ(JZP150, 0.3 mg) ≠ Δμ(Placebo) 
H05(CGI-S): Δμ(JZP150, 0.3 mg) = Δμ(Placebo) vs HA5(CGI-S): Δμ(JZP150, 0.3 mg) ≠ Δμ(Placebo) 
H06(PGI-S): Δμ(JZP150, 0.3 mg) = Δμ(Placebo) vs HA6(PGI-S): Δμ(JZP150, 0.3 mg) ≠ Δμ(Placebo) 
 
where Δμ represents mean change from baseline to end of Week 12 in the CAPS-5 total score, 
CGI-S or PGI-S.  
Specifically, for the primary endpoint, the null hypothesis states that there is no difference in the 
mean change in the CAPS-5 total score from Baseline to Week 12 between the indicated JZP150 
dose level and placebo arm. The alternative hypothesis states that the mean change in the 
CAPS- 5 total score is not equal between the indicated JZP150 dose level and placebo. 
The null and alternative hypotheses for each of the key secondary estimand variables (CGI-S and 
PGI-S) are defined similarly as for the primary efficacy estimand variable. 
 
7.4. 
Level of Significance & Multiplicity Adjustment 
A fixed sequence hierarchical testing strategy will be implemented for the primary and key 
secondary endpoints (as illustrated in Table 4) to preserve the family-wise Type 1 error rate at 
the significance level of 0.05. Testing will begin with the comparison of JZP150 4 mg vs placebo 
for the primary efficacy endpoint followed by sequential testing of the key secondary efficacy 
endpoints in the order of CGI-S and then PGI-S. If all three null hypotheses are rejected, then 
similar hierarchical sequential testing of the endpoints will be performed for comparing JZP150 
0.3 mg vs placebo. The testing will stop when the p-value exceeds the significance level of 0.05. 
All tests will be conducted at a 2-sided significance level of 0.05. Multiplicity adjustment will 
not be conducted for other secondary efficacy endpoints or for the exploratory endpoints. 
Statistical hypotheses to be tested (in sequential order): 
1. Change in the primary estimand variable (the CAPS-5 total score) from Baseline to Week 
12, JZP150 4 mg vs placebo 
2. Change in the key secondary estimand variable (CGI-S) from Baseline to Week 12, 
JZP150 4 mg vs placebo  
3. Change in the key secondary estimand variable (PGI-S) from Baseline to Week 12, 
JZP150 4 mg vs placebo  
4. Change in the primary estimand variable (the CAPS-5 total score) from Baseline to 
Week 12, JZP150 0.3 mg vs placebo  
5. Change in the key secondary estimand variable (CGI-S) from Baseline to Week 12, 
JZP150 0.3 mg vs placebo  
6. Change in the key secondary estimand variable (PGI-S) from Baseline to Week 12, 
JZP150 0.3 mg vs placebo  
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
26 
 
 
  
 
Table 4: Fixed Sequence Testing Strategy 
Sequence 
Variable 
JZP150 Dose 
Null Hypothesis 
Expected 
Effect Size 
Power 
1 
CAPS-5 
4 mg 
 H01(CAPS-5) 
0.57 
93.4% 
2 
CGI-S 
4 mg 
H02(CGI-S) 
0.50 
86% 
3 
PGI-S 
4 mg 
H03(PGI-S) 
0.50 
86% 
4 
CAPS-5 
0.3 mg 
H04(CAPS-5) 
0.57 
80.9% 
5 
CGI-S 
0.3 mg 
H05(CGI-S) 
0.50 
70% 
6 
PGI-S 
0.3 mg 
H06(PGI-S) 
0.50 
70% 
 
7.5. 
Subgroups and Subgroup Analyses 
Subgroup analyses will be conducted on the primary and key secondary efficacy endpoints for 
the following: 
 
Randomization stratum: presence vs absence of concomitant use of SSRIs/SNRIs 
 
Age group 1 (years): ≤ 65 vs > 65 
 
Age group 2 (years): ≤ 45 vs > 45 
 
Gender (male vs female) 
 
Race (white vs black vs other) 
 
Ethnicity (Hispanic or Latino vs Not Hispanic or Latino) 
 
High enrolling sites (≥ 20 randomized participants) (high enrolling sites combined vs all 
other sites combined) 
Should there be less than 20 participants in any subgroup, then only summary statistics will be 
presented.  
The output for estimating the treatment difference within subgroup will not be provided (least 
square [LS] means, standard error [SE], LS Mean Difference (95% confidence interval [CI]) or 
median difference (95% CI) and p-value) if the data are too sparse.  
It should be noted that the study was not designed to detect treatment differences with high 
statistical power within any subgroups. 
 
7.6. 
Intercurrent Event Strategies 
The main ICE of treatment discontinuation will be handled using two different strategies as 
defined below: 
The treatment policy (based on the Intention to Treat (ITT) principle, where value of the 
variable of interest is used regardless of whether the ICE occurs) will be used as the 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
27 
 
 
  
 
primary strategy to address the ICE of treatment discontinuation in the main analyses for 
the primary and key secondary estimands. It is defined as the pharmacologic effect of 
JZP150 compared to placebo over the protocol-specified treatment period (i.e., 
12 weeks), regardless of whether randomized treatment is continued. Analyses will be 
conducted using all data collected through Week 12 regardless of treatment 
discontinuation. Efficacy data collected after treatment discontinuation will be included 
in the main analyses. 
The hypothetical approach (assuming treatment discontinuation did not occur) will be 
used as the alternative strategy to address the ICE of treatment discontinuation in the 
repeated analyses for the primary and key secondary estimands. It is defined as the 
pharmacologic effect of JZP150 compared to placebo assuming continuation of 
randomized treatment for the protocol-specified treatment period (i.e., 12 weeks). 
Analyses will be conducted using only data collected at time points that are at or prior to 
treatment discontinuation. Efficacy data collected after treatment discontinuation will be 
discarded for the alternative strategy. 
Other possible ICEs include study intervention non-compliance, significant protocol deviations, 
new trauma, or initiation or adjustment of concomitant medications for PTSD, which are not 
permitted per protocol, but nevertheless can still occur. It is anticipated that the occurrence of 
these events will be rare; therefore, both primary and key secondary estimands use the treatment 
policy approach to address these other ICEs. 
For all secondary efficacy endpoints, unless specified otherwise, all ICEs will be addressed by 
the treatment policy strategy.  
 
7.7. 
Statistical Modifications  
Modifications to the statistical section of the protocol are listed as follows. 
 The protocol states “The FAS will include all participants who are randomized and took 
at least one dose of study medication. Participants are analyzed according to randomized 
treatment.” We have observed serious deviations and significant breaches to the 
principles of Good Clinical Practice during the study at Site 1865, especially in the 
collection of efficacy data. These deviations and breaches are suspected to be gross 
misconduct and thus considered to have compromised the integrity of the efficacy data 
collected and reported by this site. This SAP thus defines Full Analysis Set 1 and Full 
Analysis Set 2 to accommodate the exclusion of Site 1865 from efficacy analyses. 
 The protocol states that “The mFAS population will include all participants who are 
randomized, took at least one dose of study medication, and have baseline and any post-
baseline assessment of CAPS-5 total score, CGI-S, or PGI-S score, excluding ineligible 
participants that were randomized”. This SAP defines the Modified Full Analysis Set as 
“includes all participants in the Full Analysis Set 1 who have baseline and at least 1 post-
baseline assessment of CAPS-5 total score, CGI-S, or PGI-S score, excluding ineligible 
participants that were randomized” to accommodate the exclusion of Site 1865 from the 
supplementary efficacy analyses using mFAS. 
 The protocol states "the mFAS analysis set will be the primary analysis set for all 
efficacy analyses.” At FDA’s recommendation to use FAS, this SAP defines the main 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
28 
 
 
  
 
efficacy analysis set as “The Full Analysis Set 1 which includes all participants who were 
randomized and took at least 1 dose of the study intervention, excluding Site 1865.” This 
analysis set will be the primary analysis set for all efficacy analyses.  
 The protocol states that time-dependent multiple imputation will be included as a 
sensitivity analysis. Due to limited collection of post-ICE efficacy follow up data, the 
time-dependent multiple imputation will not produce robust estimates and therefore will 
not be included in this SAP. 
 The protocol states that the 2-dimentional tipping point analysis will be included as a 
sensitivity analysis. This SAP will use the traditional 1-dimentional tipping point analysis 
to include more details in the results display, such as LS means, LS mean differences, SE, 
and 95% CI, that are associated with different deltas (shifts). 
 The protocol states that “The PK Analysis Set will include all participants who receive at 
least 1 dose of study intervention and have at least 1 pre-dose or 1 post-dose evaluable 
PK concentration.” This SAP has been modified to “The PK Analysis Set will include all 
participants who receive at least 1 dose of study intervention and have at least 1 post-dose 
(post first dose) evaluable PK concentration.” 
 
8. 
STUDY POPULATION SUMMARIES 
8.1. 
Enrollment 
The total number and percentage of participants for each Analysis Set defined in Section 6 will 
be summarized overall and by randomized treatment group.   
8.2. 
Participant Disposition 
All participants who provide signed ICF will be accounted for in this study. The number and 
percentages of screen failure participants will be presented by overall among the Enrolled 
Analysis Set. The number and percentages of participants who received at least one dose, 
completed, discontinued early from study intervention, and discontinued early from study, 
including reasons for early discontinuation, will be presented overall and by randomized 
treatment group among the Enrolled Analysis Set and Full Analysis Set 2. The number and 
percentage of participants by study site/Investigator will also be summarized among the Enrolled 
Analysis Set and Full Analysis Set 2. 
A concordance analysis using Cohen’s kappa will be conducted using the Full Analysis Set 1 to 
examine the agreement of the classification of participants into randomization strata using 
different data sources, i.e., the IRT vs the electronic data capture (EDC). In case of discrepancies 
between IRT and EDC, the randomization stratum recorded in IRT will be used in efficacy 
analyses and the randomization stratum recorded in EDC will be used in safety analyses.   
The following provides the example SAS code for the Cohen’s kappa analysis: 
PROC FREQ; 
TABLE IRT*EDC / AGREE; 
RUN; 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
29 
 
 
  
 
A participant is considered to have completed the study intervention if he/she has completed the 
double-blinded treatment period, including receipt of 12 weeks of study intervention. A 
participant is considered to have completed the study if he/she has completed all periods of the 
study including the last scheduled procedure in the safety follow-up visit. The participants who 
discontinue the study intervention early but remain in the study are not considered study 
completers. 
Note that the participant disposition listing will capture the reason for withdrawal including any 
participant who discontinues from the study due to acquisition of COVID-19 (or other) 
pandemic. 
8.3. 
Demographic and Baseline Characteristics 
Demographics and baseline data will be summarized by randomized treatment group and overall 
for the Full Analysis Set 1, PK, and PD Analysis Sets and by treatment group and overall for the 
Safety Analysis Set. The denominators for calculating the percentages of categorical variables 
will be the number of participants in each analysis set.  
Demographics and baseline characteristics to be summarized include: 
 The age derived from date of birth and informed consent date will be used.  
 Age groups as defined in Section 7.5 
 Gender  
 Race. Participants who reported more than one race will be reported under ‘multiple’ race 
category.  
 Ethnicity  
 Height (cm), weight (kg), and body mass index (BMI) (kg/m2) at Baseline 
 Childbearing potential   
 Presence of concomitant use of SSRIs/SNRIs at Baseline 
Other baseline characteristics such as MINI, C-SSRS (baseline/screening version), LEC-5, and 
medication washout during Screening will be listed. C-SSRS and LEC-5 will be summarized. 
 
8.4. 
Medical History 
Medical/surgical history are defined as those medical/surgical conditions which started prior to 
study intervention. The medical/surgical history data will be summarized by treatment group and 
overall for the Safety Analysis Set and by randomized treatment group and overall for the Full 
Analysis Set 2.  
Medical/surgical history reported terms will be coded to a System Organ Class (SOC) and 
Preferred Term (PT) using the most recent version of the Medical Dictionary for Regulatory 
Activities (MedDRA) dictionary version (24.0 or later). Participants’ Medical/surgical history 
data (other than PTSD) by SOC and PT for each of the analysis sets will be summarized. A 
participant with multiple medical conditions will be counted once per SOC and PT. The 
summary table will be sorted by descending order of frequency of SOC in the JZP150 4 mg 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
30 
 
 
  
 
treatment arm (then alphabetically for ties), then by descending order of frequency of PT within 
each SOC (then alphabetically for ties). 
The PTSD disease history will be summarized for the Safety Analysis Set and the Full Analysis 
Set 1. Key disease history variables include: 
 Time since PTSD symptom onset and initial diagnosis (years) – calculated relative to 
date of ICF signing (See for handling partial dates) 
 Name and status of psychotherapy, if any 
 Listings will also be provided for medical/surgical history and PTSD disease history.  
 
8.5. 
Prior and Concomitant Medications 
Medications will be coded to the anatomical therapeutic class (ATC) level 4 and preferred drug 
name using the World Health Organization (WHO) drug dictionary, version 
GLOBALB03Mar2021 or later, and will be classified as follows (See Appendix 2 for handling 
of partial dates for medications):  
 
Prior medications are defined as any protocol-specified collection of medications which 
have an end date before the first dose of study intervention. 
 
Concomitant medications are defined as any medication which started prior to and is 
ongoing at the time of first dose of study intervention or is started on or after the first 
dose of study administration up to the last dose of study intervention.  
 
Post medications are defined as any medications which started after the last dose of 
study intervention.  
Medications will be summarized by ATC level 4 and preferred drug name. Additionally, disease-
related medications will also be summarized and defined as those medications taken for the 
treatment of PTSD symptoms.  
Summaries will include all prior medication, disease-related prior medications, concomitant 
medications, and disease-related concomitant medications by overall and treatment group in the 
Safety Analysis Set.  
Disease-related prior and concomitant medications will also be summarized by overall and by 
randomized treatment groups using the Full Analysis Set 1. 
All prior, concomitant, and post medications will be included in a data listing. Post medications 
will be flagged in the data listing but will not be summarized. 
 
8.6. 
Protocol Deviations 
Protocol deviations as classified in the Clinical Trial Management System (CTMS) will be 
summarized using the Full Analysis Set 2 by type of deviation and severity (important or non-
important). All protocol deviations will also be provided in a data listing.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
31 
 
 
  
 
If changes to study conduct occur due to COVID-19 restrictions, they will be reported as 
protocol deviations. These deviations will be summarized separately by the classification type in 
CTMS and included in a data listing. 
Discrepancies between IRT and EDC (i.e., wrong randomization stratum recorded in IRT) will 
be reported as protocol deviations. The approach to address these discrepancies is described in 
Section 8.2 and Section 9.1.3.4.  
Dosing in error will be reported as protocol deviations. The mis-dosed participants will be 
summarized by their randomized treatment arm in efficacy analyses. For safety analyses, the 
mis-dosed participants will be summarized by their treatment arm determined by the first actual 
dose.  
9. 
EFFICACY  
Unless otherwise described, efficacy data will be primarily summarized by randomized treatment 
groups using the Full Analysis Set 1, and treatment comparison will be conducted between the 
randomized treatment groups verses placebo. Efficacy data will be summarized using descriptive 
statistics by time point. Data listings will also be presented for all efficacy endpoints. The 
Modified Full Analysis Set and Full Analysis Set 2 will be used in supplementary analyses for 
efficacy endpoints. 
Efficacy data from Site 1865 was excluded from the primary analysis set Full Analysis Set 1 due 
to observed serious deviations and significant breaches to the principles of Good Clinical 
Practice during the study, especially in the collection of efficacy data. These deviations and 
breaches are suspected to be gross misconduct and thus considered to have compromised the 
integrity of the efficacy data collected and reported by this site. A supplemental analysis using 
Full Analysis Set 2 will be conducted which does include this site’s efficacy data.   
9.1. 
Primary Efficacy Estimand and Analysis 
9.1.1. 
Primary Estimand 
The attributes of the primary estimand are described in Section 4.2.1. 
The CAPS-5 is a structured, clinician administered, clinical interview wherein participants report 
on their symptoms of PTSD (Weathers et al 2018). The CAPS-5 will be administered by 
qualified medical personnel (i.e., principal investigator, clinical rater). It is a well-established, 
widely used, and validated assessment that captures PTSD symptom frequency and intensity 
over the past week using a 5-point Likert-type rating scale. 
The CAPS-5 total score is derived by summing the scores over the 20 items from the 4 PTSD 
symptom clusters/subscales: intrusive symptoms (items B1, B2, B3, B4, and B5), avoidance 
symptoms (items C1 and C2), arousal/reactivity symptoms (items E1, E2, E3, E4, E5, and E6), 
and negative alterations in mood and cognition (items D1, D2, D3, D4, D5, D6, and D7). Each 
item is rated with a single severity score on a 5-point rating scale (0-4) corresponding to the 
following categories: 0- Absent, 1- Mild/subthreshold, 2- Moderate/threshold, 3- 
Severe/markedly elevated, and 4- Extreme/incapacitating. The CAPS-5 total score ranges 
between 0 and 80. The intrusive symptoms subscale score ranges between 0 and 20; the 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
32 
 
 
  
 
avoidance symptoms subscale score ranges between 0 and 8; the arousal/reactivity symptoms 
subscale score ranges between 0 and 24; and the negative alterations in mood and cognition 
subscale score ranges between 0 and 28. Higher scores indicate more severe PTSD symptoms. 
The CAPS-5 total score is assessed at Baseline and end of Weeks 4 and 12. 
9.1.2. 
Main Analyses  
The main analysis for the primary estimand will be conducted based on the Full Analysis Set 1, 
using treatment policy to address all ICEs. All CAPS-5 total score data collected through Week 
12 regardless of ICEs will be used in the analysis, including the CAPS-5 total score data 
collected after an ICE. Using the main ICE of treatment discontinuation as the example, Table 5 
describes the detailed data mapping method for CAPS-5 total score scores following treatment 
discontinuation.    
Table 5. Data mapping for CAPS-5 total score following treatment discontinuation for the 
main analyses. 
Intercurrent event  
CAPS-5 total score data mapping 
If participant discontinues both study 
intervention and the study 
CAPS-5 total score at E/D or any 
unscheduled visit will be mapped to Week 
4 or Week 12, according to the windowing 
rule in Section 7.2.3.  
If participant discontinues study intervention 
prior to Week 4 but remains in the study 
CAPS-5 total score at E/D visit, any 
unscheduled visit, the additional efficacy 
follow-up for Week 4, or efficacy follow-
up visit for Week 12 will be mapped to 
Week 4 or Week 12, according to the 
windowing rule in Section 7.2.3. 
If participant discontinues study intervention 
between Week 4 and Week 12 but remains in the 
study 
CAPS-5 total score at E/D visit, any 
unscheduled visit, or efficacy follow-up 
visit for Week 12 will be mapped to Week 
12, according to the windowing rule in 
Section 7.2.3. 
A mixed-effect model with repeated measures (MMRM) will be used to analyze the primary 
efficacy endpoint, change in CAPS-5 total score from Baseline to Week 12. 
 𝑑𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖𝑗= 𝛼𝑖+ 𝛽1 ∗𝑏𝑎𝑠𝑒𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖 + 𝛽2 ∗𝑤𝑒𝑒𝑘𝑗+ 𝛽3 ∗𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑖  + 𝛽4 ∗
𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑖∗ 𝑤𝑒𝑒𝑘𝑗 + 𝛽5 ∗𝑏𝑎𝑠𝑒𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖∗ 𝑤𝑒𝑒𝑘𝑗 + 𝛽6 ∗𝑠𝑡𝑟𝑎𝑡𝑢𝑚𝑖  + 𝛽7 ∗𝑠𝑡𝑟𝑎𝑡𝑢𝑚𝑖∗ 𝑤𝑒𝑒𝑘𝑗 +
 𝜀𝑖𝑗 
The model will include the CAPS-5 total score change from Baseline to Week 12 
(𝑑𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖𝑗) as the dependent variable; randomized treatment group (𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑖  ), 
CAPS-5 total score at Baseline (𝑏𝑎𝑠𝑒𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖), week (as a discrete factor, 𝑤𝑒𝑒𝑘𝑗), 
treatment group by week interaction (𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡𝑘∗ 𝑤𝑒𝑒𝑘𝑗 ), baseline by week interaction 
(𝑏𝑎𝑠𝑒𝐶𝐴𝑃𝑆5𝑇𝑜𝑡𝑎𝑙𝑆𝑐𝑜𝑟𝑒𝑖∗ 𝑤𝑒𝑒𝑘𝑗 ), randomization stratum (𝑠𝑡𝑟𝑎𝑡𝑢𝑚𝑖  ), and stratum by week 
interaction (𝑠𝑡𝑟𝑎𝑡𝑢𝑚𝑖  ∗𝑤𝑒𝑒𝑘𝑗 ) as fixed effects, and week as a repeated effect.  
SAS Proc Mixed with restricted maximum likelihood estimation (REML) will be used and an 
unstructured within-participant covariance structure will be applied to model the correlation 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
33 
 
 
  
 
among repeated measurements. If the model fails to converge on the default Newton-Raphson 
algorithm, the alternative Fisher scoring algorithm should be explored before considering other 
variance-covariance structures (Lu and Mehrotra 2010). The Kenward-Roger approximation will 
be used to estimate denominator degrees of freedom for tests of fixed effects. Missing data will 
not be explicitly imputed and will be handled with the MMRM modeling.  
LS means, SE and 95% CI for Week 12 will be provided for each randomized treatment group. 
The difference between the LS means of an active treatment group and placebo for Week 12, 
along with the SE of the difference, 95% CI and associated p-value corresponding to testing the 
hypothesis of no difference between the treatment groups will also be provided. Summary 
statistics of CAPS-5 total score by time point for each treatment group based on the Full 
Analysis Set 1 will also be provided. 
If the unstructured covariance fails to converge, the following covariance structures will be 
tested in order: 
 Toeplitz with heterogeneity by visit 
 Autoregressive with heterogeneity by visit 
 Compound symmetry with heterogeneous variances by visit 
 Toeplitz 
 Autoregressive 
 Compound symmetry without heterogeneous variances by visit 
If structured covariance matrix is used, a sandwich variance estimator will be applied 
simultaneously to address the potential mis-specification of the covariance matrix. 
A box plot of the change in the CAPS-5 total score from Baseline to end to Week 12 by 
randomized treatment group will be presented. The CAPS-5 total score data will also be 
summarized by time point and the change from baseline to each time point will be displayed as a 
figure.  
Following provides the example SAS code for the MMRM model used in the main analysis. 
PROC MIXED DATA =ANAL; 
CLASS PATIENT TRT WEEK STRATUM; 
MODEL CHG = BASE TRT WEEK TRT*WEEK BASE* WEEK STRATUM STRATUM* 
WEEK / DDFM=KR RESIDUAL OUTP=RESIDUAL;  
REPEATED WEEK/TYPE=UN SUB=PATIENT;  
LSMEANS TRT*WEEK / CL DIFF ALPHA=0.05; 
RUN; 
The option of “EMPIRICAL” will be applied in the PROC MIXED procedure above if 
structured covariance matrix is used. 
9.1.3. 
Sensitivity Analyses  
9.1.3.1. 
Tipping Point Analysis 
The main efficacy analysis of the primary and key secondary efficacy estimand includes all 
CAPS-5 total score, CGI-S score, and PGI-S score data collected following any ICEs for 
participants who remain in the study and assumes that any remaining missing data due to ICEs is 
missing at random (MAR). To examine the departure of the main efficacy analysis results from 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
34 
 
 
  
 
the MAR assumption in the MMRM modeling, a tipping point analysis will be performed to 
‘stress test’ the robustness of the main efficacy analysis based on the Full Analysis Set 1. 
This method involves a 3-step approach: 
Step 1: The MCMC method will be used in conjunction with the IMPUTE=MONOTONE option 
to create an imputed dataset with a monotone missing pattern. 
Step 2: Using the monotone dataset from step 1, missing data will be imputed using the 
MONOTONE REGRESSION method. Participants who experienced an ICE such as treatment 
discontinuation earlier than Week 12 will have missing data imputed first assuming a MAR 
mechanism.  
Step 3: A “marginal delta” or “shift” will be added to Week 12 for one specific JZP150 treatment 
arm prior to analyzing the imputed datasets (number of imputations=20) and combining the 
results using the same MAR assumption and MMRM modeling as in step 2. The deltas to be 
investigated are multiples of the observed treatment effect. If the absolute value of LS Mean 
Difference at week 12 from the MMRM modeling in the main analysis is X, the deltas to be 
investigated will range from -X to +3X for one specific JZP150 treatment arm, in increments of 
0.2X, for example. The increment or range may be further refined based on the analysis results 
and the location of tipping point. The X from the JZP150 4 mg vs placebo comparison in the 
main analysis will also be used for the tipping point analysis between JZP150 0.3 mg vs placebo. 
The imputed datasets will be analyzed using the same MMRM model described in Section 9.1.2. 
Results will be combined using Rubin’s rule (Rubin 1987) for the estimation of treatment effect 
at Week 12. 
Step 1 may be omitted if missing data are completely monotone. 
The imputation model for step 1 and step 2 will include the auxiliary variable randomization 
stratum and the values of the analyzed parameter at baseline and planned visits up to Week 12. 
The imputation in both steps will be performed separately for each treatment arm. The number of 
imputations will be 20 in step 1 and 1 in step 2. If step 1 is omitted, then the number of 
imputations in step 2 will be 20.  
JZP150 and placebo arms will be imputed 20 times based on the MAR assumption. For each of 
the imputations, the relevant deltas will be added to Week 12 for the JZP150 treatment arm. The 
modified imputations will be then analyzed using the same MMRM model in step 2 and the 
results will be combined.  
The values of the imputed variables will be restricted within the ranges of minimum and 
maximum possible values. 
The following SAS code can be used to perform the tipping point analysis. 
 
%MACRO TPA1 (DATA=, SMIN=, SMAX=, SINC=, OUT=); 
DATA &OUT; 
SET _NULL_; 
RUN; 
/*------------ # OF SHIFT VALUES ------------*/ 
%LET NCASE= %SYSEVALF( (&SMAX-&SMIN)/&SINC, CEIL ); 
/*------- IMPUTED DATA FOR EACH SHIFT -------*/ 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
35 
 
 
  
 
%DO JC=0 %TO &NCASE; /*NCASE IS THE NUMBER OF TOTAL SHIFTS TO BE 
EVALUATED*/ 
%LET SJ= %SYSEVALF( &SMIN + &JC * &SINC); /*SJ IS THE SHIFT VALUE*/ 
PROC MI DATA=&DATA SEED=439384924 NIMPUTE=20 OUT=MONO 
MINIMUM=0 0 0 0 
MAXIMUM=1 80 80 80  
MINMAXITER=9000; 
MCMC IMPUTE=MONOTONE NBITER=200 NITER=200; 
VAR STRATUM BASE WEEK4 WEEK12;  
BY TRT; 
RUN; 
PROC MI DATA=MONO SEED=439384924 NIMPUTE=1 OUT=OUTMI  
MINIMUM=0 0 0 0 
MAXIMUM=1 80 80 80  
MINMAXITER=9000; 
CLASS TRT; 
VAR STRATUM TRT BASE WEEK4 WEEK12; 
MONOTONE REGRESSION (BASE STRATUM WEEK4 WEEK12); 
MNAR ADJUST(WEEK12 / SHIFT=&SJ.  ADJUSTOBS=(TRT='1'  '2'));  
BY TRT _IMPUTATION_; 
RUN; 
DATA OUTMI; 
SET OUTMI; 
SHIFT= &SJ; 
RUN; 
DATA &OUT; 
SET &OUT OUTMI; 
RUN; 
%END; 
%MEND TPA1; 
 
%TPA1 (DATA=ANAL_MONO, SMIN=-&X., SMAX=3&X., SINC=0.2&X., OUT= TPA1); 
 
/*CALCULATE CHG AND TRANSPOSE DATA BEFORE RUNNING MMRM MODEL*/ 
PROC MIXED DATA= ANAL_TPA1; 
CLASS PATIENT TRT WEEK STRATUM; 
MODEL CHG = BASE TRT WEEK TRT*WEEK BASE* WEEK STRATUM STRATUM* 
WEEK / DDFM=KR RESIDUAL OUTP=RESIDUAL; 
REPEATED WEEK/TYPE=UN SUB=PATIENT; 
LSMEANS TRT*WEEK / CL DIFF ALPHA=0.05; 
ODS OUTPUT DIFFS=LSDIFFS (where=(TRT=0 and TRT=1 and WEEK=12 and 
_WEEK=12)); 
BY SHIFT _IMPUTATION_; 
RUN; 
 
PROC MIANALYZE DATA=LSDIFFS; 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
36 
 
 
  
 
MODELEFFECTS ESTIMATE; 
STDERR STDERR; 
BY SHIFT; 
ODS OUTPUT PARAMETERESTIMATES=TIPDIFFS; 
RUN; 
 
9.1.3.2. 
Control-based Pattern Mixture Imputation 
For both the primary and key secondary efficacy endpoints, a control-based pattern mixture 
model will be used to explore the possibility of the missing data being missing not at random 
(MNAR) for the participants who discontinued study intervention but provided no post-
discontinuation efficacy data for the main analysis.  
These participants will be categorized based on their reason of treatment discontinuation. If the 
reason is ‘lack of efficacy’ or ‘adverse events’, the participant will be categorized as ‘treatment-
related discontinuation’. If it is due to any other reason, the participant will be categorized as 
‘treatment-unrelated discontinuation’.    
For the participants having treatment-related discontinuation, missing data will be imputed using 
the ‘copy reference’ imputation where the mean and variance based on the placebo group 
(reference) will be assumed for both Week 4 and Week 12 data for the primary endpoint, for 
example (O’Kelly and Ratitch, 2014). For the participants having treatment-unrelated 
discontinuation, missing data will be imputed assuming MAR.  
Similar to step 1 and step 2 in tipping point analysis, 20 imputed datasets will be generated 
assuming a MAR mechanism for missing data. For the participants having treatment-related 
discontinuation, the imputed Week 4 and Week 12 data will be discarded in each of these 20 
datasets and replaced by MNAR imputations. The final imputed datasets with a mixture of MAR 
and MNAR imputations will be analyzed separately using the MMRM model specified in 
Section 9.1.2.  
The MIANALYZE procedure will be used to generate valid statistical inferences by 
combining results from the 20 analyses. 
The following SAS code can be used for the MNAR imputation. 
PROC MI DATA=ANAL_COMPL SEED=439384924 NIMPUTE=1 OUT=ANAL_MNAR; 
MINIMUM = 1 0 0 0 ;  
MAXIMUM = 2 80 80 80.; 
CLASS TRT; 
VAR STRATUM  BASE WEEK4 WEEK12; 
MONOTONE REGRESSION (/DETAILS); 
MNAR MODEL(WEEK4 WEEK12 / MODELOBS= (TRT='0')); 
BY _IMPUTATION_; 
RUN; 
 
9.1.3.3. 
Non-parametric Analysis  
Non-parametric analysis may be performed to examine the departure from the parametric 
assumption for the MMRM model used in the main analysis of the primary efficacy estimand, if 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
37 
 
 
  
 
there is strong evidence of non-normality. In this sensitivity analysis, the p-value for comparing 
treatments for the primary endpoint will be reported from a non-parametric MMRM model with 
the response and baseline covariate variables replaced by their ranks. In the event of ties in the 
baseline or change from baseline, average ranks will be used. The ranks will be used in the 
MMRM with the rank for the change from baseline as the dependent variable; treatment, week 
(as a discrete factor), treatment group by week interaction, randomization stratum and ranked 
baseline CAPS-5 total score as fixed effects. P-values will be presented from the rank-based 
MMRM. The estimated median difference between the change in CAPS-5 total score between 
each treatment group and placebo, and asymptotic 95% CIs will be presented using the Hodges-
Lehmann estimator (Hodges and Lehmann 1962). 
The following SAS code will be used. 
PROC RANK DATA =ANAL OUT=RANKED TIES=MEAN;  
VAR BASE CHG;  
RANKS RBASE RCHG;  
RUN; 
 
PROC MIXED DATA=RANKED;  
CLASS  PATIENT TRT WEEK STRATUM;  
MODEL RCHG = RBASE TRT WEEK TRT*WEEK RBASE* WEEK STRATUM 
STRATUM* WEEK / DDFM=KR RESIDUAL OUTP=RESIDUAL; 
REPEATED WEEK/TYPE=UN SUB=PATIENT; 
RUN; 
 
An estimate of the median difference between treatments for the primary endpoint will be 
reported using Hodges-Lehmann analysis.  
PROC NPAR1WAY HL ALPHA=.05 DATA=ANAL;  
CLASS TRT;  
VAR CHG;  
RUN; 
 
9.1.3.4. 
Additional Sensitivity Analyses 
Additional sensitivity analyses may be performed by using the randomization stratum recorded 
in EDC in case of discrepancies between IRT and EDC.
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
38 
 
 
  
 
9.1.4. 
Subgroup Analyses 
Subgroup analyses for groups specified in Section 7.5 will be performed for the primary efficacy 
estimand using the Full Analysis Set 1, for each of the prespecified subgroups. Subgroup 
variable by treatment interaction will be estimated for Week 12. Normality assumptions will not 
be reassessed for subgroups. The corresponding parametric or nonparametric analysis used for 
the overall sample will be applied to each subgroup. Numeric results for subgroup analyses will 
be summarized. A forest plot summarizing the treatment difference, 95% CI, and p-value for the 
interaction term estimated at Week 12 will also be provided by each subgroup. 
9.1.5. 
Supplementary Analyses 
 Alternative ICE Strategy: The main analysis for the primary estimand in Section 9.1.2 
will be repeated based on the Full Analysis Set 1, using hypothetical approach to address 
the main ICE of treatment discontinuation. The hypothetical approach assumes that 
results for participants with the ICE would have followed the same trajectory as 
participants in the same treatment group who didn’t have the ICE. Only the CAPS-5 total 
score data collected at time points that are at or prior to treatment discontinuation will be 
included in the analysis. The CAPS-5 total score data collected after any treatment 
discontinuation will be discarded. Missing data will not be imputed and will be addressed 
with the same MMRM model described in Section 9.1.2. 
 Alternative Analysis Set: The main analysis for the primary estimand will be repeated 
using the Modified Full Analysis Set and Full Analysis Set 2. 
 
9.2. 
Secondary Efficacy Estimands, Endpoints and Analyses 
9.2.1. 
Key Secondary Estimands  
The attributes of the key secondary efficacy estimands are described in Section 4.2.2. 
The Key Secondary Estimand 1 variable CGI-S is a 7-point Likert-type rating scale used to 
assess the severity of participants’ PTSD over the past week by qualified medical personnel (i.e., 
principal investigator, clinical rater). The responses to this investigator-completed scale range 
from 1 (Normal, not at all ill) to 7 (Among the most extremely ill participants).  
The Key Secondary Estimand 2 variable PGI-S is a 5-point Likert-type rating scale used to 
assess the severity of PTSD over the past week by study participants. The responses to this 
participant-completed scale range from 1 (None) to 5 (Very severe).  
CGI-S and PGI-S are assessed at Baseline and end of Weeks 1, 4, 8, and 12. 
9.2.2. 
Key Secondary Estimands Main Analysis 
The main analysis for the key secondary estimands will be conducted based on the Full Analysis 
Set 1, using treatment policy to address all ICEs. All CGI-S and PGI-S data collected through 
Week 12 regardless of ICEs will be used in the analysis, including the CGI-S and PGI-S data 
collected after an ICE. Using the main ICE of treatment discontinuation as the example, Table 7 
describes the detailed data mapping method for CGI-S and PGI-S following treatment 
discontinuation.    
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
39 
 
 
  
 
Table 7. Data mapping for CGI-S and PGI-S following treatment discontinuation for the 
main analyses. 
Intercurrent event  
CGI-S and PGI-S data mapping 
If participant discontinues both study 
intervention and the study 
CGI-S and PGI-S at E/D visit, any unscheduled 
visit, or safety follow-up will be mapped to Week 4 
and/or Week 12, according to the windowing rule 
in Section 7.2.3. 
If participant discontinues study 
intervention prior to Week x but remains 
in the study (x=1, 4, or 8) 
CGI-S and PGI-S scores at E/D visit, any 
unscheduled visit, the additional efficacy follow-up 
for Week 4, efficacy follow-up visit for Week 12 or 
safety follow-up will be mapped to Week 1, 4, 8, or 
Week 12, according to the windowing rule in 
Section 7.2.3. 
If participant discontinues study 
intervention between Week x and Week 
12 but remains in the study (x=1, 4, or 
8) 
CGI-S and PGI-S scores at E/D visit, any 
unscheduled visit, efficacy follow-up visit for 
Week 12 or safety follow-up will be mapped to 
Week 12, according to the windowing rule in 
Section 7.2.3. 
The CGI-S and PGI-S scores will be considered as continuous variables. A MMRM will be used 
to analyze the key secondary efficacy endpoints, change in CGI-S and PGI-S from Baseline to 
Week 12, respectively.  
The model will include CGI-S or PGI-S change from Baseline to Week 12 as the dependent 
variable; randomized treatment group, week (as a discrete factor), treatment group by week 
interaction, randomization stratum, stratum by week interaction, the CGI-S or PGI-S score at 
Baseline, and baseline by week interaction, as fixed effects, and week as a repeated effect. An 
unstructured variance-covariance matrix will be used to model the correlation among repeated 
measurements. Missing data will not be explicitly imputed and will be handled with the MMRM 
modeling. Alternative covariance structures will be similar to the methodology specified in 
Section 9.1.2. Similar summary statistics described in Section 9.1.2 will be provided. Similar 
SAS codes provided in Section 9.1.2 will be used.  
A box plot will be presented for the change in CGI-S and PGI-S from Baseline to end to 
Week 12 by randomized treatment group, separately. The CGI-S and PGI-S data will also be 
summarized by time point separately.  
A separate SAP will be provided for the anchor-based global assessment to determine CAPS-5’s 
clinically meaningful within-patient change threshold, using CGI-S and PGI-S as anchor scales. 
This supplemental SAP will present analyses intending to support the analysis of the CGI-S and 
PGI-S assessment as continuous variables. 
9.2.3. 
Key Secondary Estimands Sensitivity Analyses 
Sensitivity analyses similar to Section 9.1.3 will be conducted for the key secondary estimands 
CGI-S and PGI-S separately.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
40 
 
 
  
 
9.2.4. 
Key Secondary Estimands Subgroup Analyses 
Subgroup analyses similar to Section 9.1.4 will be conducted for the key secondary estimands 
CGI-S and PGI-S separately.   
9.2.5. 
Key Secondary Estimands Supplementary Analyses  
• 
Alternative ICE Strategy: The main analysis for the key secondary estimands will be 
repeated based on the Full Analysis Set 1, using hypothetical approach to address the main ICE 
of treatment discontinuation. The hypothetical approach assumes that results for participants with 
the ICE would have followed the same trajectory as participants in the same treatment group 
who didn’t have the ICE. Only the CGI-S or PGI-S collected at time points that are at or prior to 
treatment discontinuation will be included in the analysis. The CGI-S or PGI-S collected after 
any treatment discontinuation will be discarded. Missing data will not be imputed and will be 
addressed with the same MMRM model described in Section 9.2.2. 
• 
Alternative Analysis Set: The main analysis for key secondary estimands will be repeated 
using the Modified Full Analysis Set and Full Analysis Set 2. 
9.2.6. 
Other Secondary Efficacy Endpoints and Analyses 
The analysis for all secondary efficacy endpoints, unless specified otherwise, will be based on 
the Full Analysis Set 1 with all ICEs addressed by the treatment policy strategy. No sensitivity 
analysis, subgroup analysis, or supplementary analyses will be considered for any secondary 
efficacy endpoint. No multiplicity adjustment will be considered for any secondary efficacy 
endpoint. Missing data will not be explicitly imputed for any secondary efficacy endpoint.  
 
9.2.6.1. 
 Responder Analysis 
The responders are defined in 3 ways in Section 4.2.3. Three separate responder analyses will be 
performed for the CAPS-5 total score, CGI-C, and PGI-S responders. Missing data will not be 
imputed for responder analysis. 
The CGI-C is a 7-point Likert-type rating scale widely used to assess efficacy in clinical drug 
trials (Guy 1976). Investigators or trained raters will rate their impression of any change in the 
severity of the participant’s condition since Baseline on a 7-point scale ranging from 1 (very 
much improved) to 7 (very much worse). Ratings will focus on the participants’ change in their 
ability to function due to PTSD. CGI-C is assessed at end of Weeks 4 and 12. The CGI-C 
responder analysis will be performed for Week 4 and Week 12 separately.  
In each responder analysis, the proportion of participants will be compared between each dose of 
JZP150 and placebo using the Cochran-Mantel-Haenszel (CMH) test stratified by randomization 
stratum. The point estimate and continuity corrected Wilson’s 95% CI (as modified by 
Newcombe) for the difference of the proportion will also be provided.  
Example SAS Code for obtaining the CMH test p-value, point estimate and 95% CI for the 
difference in proportion is provide below: 
PROC FREQ DATA=ANAL;  
TABLES STRATUM*TRT*RESPONDER1/CMH;  
RUN;  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
41 
 
 
  
 
PROC FREQ DATA=ANAL;  
TABLES TRT*RESPONDER1/RISKDIFF(CL=(WILSON(CORRECT)));  
RUN; 
9.2.6.2. 
CAPS-5 total score change from Baseline to Week 4 
The CAPS-5 total score is described in Section 9.1.1. The results for the change in the CAPS-5 
total score from Baseline to Week 4 will be presented using the Week 4 contrasts of the MMRM 
modeling results for the primary endpoint (the CAPS-5 total score from Baseline to Week 12). 
The modeling details are described in Section 9.1.2. 
9.2.6.3. 
Change in B-IPF and SDS from Baseline to Week 12.  
The B-IPF is a 7-item participant-reported questionnaire that assesses PTSD-related psychosocial 
functional impairment in the past 30 days and is assessed at Baseline and end of Week 12. The 
B-IPF score is derived from the 7 questions regarding functional impairment. The questions are 
rated on a 7-point scale from 0 (Not at all), 1 to 5 (Somewhat), to 6 (Very much). The B-IPF 
total score is calculated by summing individual question scores, dividing by the number of 
questions and then by 6 and multiplying by 100. The B-IPF total score ranges from 0 to 100. 
The SDS is a 5-item participant-reported tool that assesses functional impairment in 
work/school, social life, and family life in the past week. The SDS score is derived from the 3 
questions on disability and impairment. The questions are rated on a 11-point scale from 0 (Not 
at all), 1-3 (Mildly), 4-6 (Moderately), 7-9 (Markedly), and 10 (Severely). The SDS score ranges 
from 0 to 30 and is assessed at Baseline and end of Weeks 4 and 12.  
The change in the B-IPF score from Baseline to Week 12 will be analyzed using an analysis of 
covariance (ANCOVA) model. The model will include B-IPF score change from Baseline to 
Week 12 as the dependent variable and randomized treatment group, randomization stratum, and 
B-IPF score at Baseline as covariates.  
Group comparisons from the ANCOVA model will be based on Type III sum of squares. LS 
means and SE will be provided for each randomized treatment group. The difference between the 
LS means along with the SE of the difference, 95% CI and associated p-value corresponding to 
testing the hypothesis of no difference between the randomized treatment groups will also be 
provided.  
The normality assumption of the ANCOVA model will be examined by residual analysis using 
the Shapiro-Wilk test (Shapiro and Wilk 1965). Outliers will be examined and if there is clear 
evidence of non-normality, a non-parametric ANCOVA with the covariate and response 
variables replaced by their ranks (Conover and Iman 1982) will be used. In the event of ties in 
the baseline or change from baseline, average ranks will be used. The non-parametric ANCOVA 
will include the rank of the B-IPF score change from baseline to Week 12 as the dependent 
variable and randomized treatment group, randomization stratum, and the rank for B-IPF score at 
Baseline as a covariate. P-values will be presented from the rank-based ANCOVA. The 
estimated median difference between the change in B-IPF score from Baseline to Week 12 
between randomized treatment groups and asymptotic 95% CIs will be presented using the 
Hodges-Lehmann estimator (Hodges and Lehmann 1962). 
The example SAS Code for the ANCOVA model is provided below: 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
42 
 
 
  
 
PROC MIXED DATA =ANAL METHOD =TYPE3;  
CLASS TRT STRATUM;  
MODEL CHG = TRT BASE STRATUM/ DDFM=KR RESIDUAL OUTP=RESIDUAL;  
LSMEANS TRT/DIFF CL;  
RUN;  
The example SAS code below evaluates the assumption of normality for the residuals from the 
above ANCOVA model using the Shapiro Wilk test (Shapiro and Wilk 1965).  
PROC UNIVARIATE DATA=RESIDUAL NORMAL;  
VAR RESID;  
RUN; 
The example SAS code for the non-parametric ANCOVA model is provided below:  
PROC RANK DATA =ANAL OUT=RANKED TIES=MEAN;  
VAR BASE CHG;  
RANKS RBASE RCHG;  
RUN;  
PROC MIXED DATA=RANKED METHOD=TYPE3;  
CLASS TRT STRATUM;  
MODEL RCHG = TRT RBASE STRATUM / DDFM=KR RESIDUAL OUTP=RESIDUAL;  
RUN;  
An estimate of the median difference between treatments for the primary endpoint will be 
reported using Hodges and Lehmann analysis.  
PROC NPAR1WAY HL ALPHA=.05 DATA=ANAL;  
CLASS TRT;  
VAR CHG;  
RUN; 
The change in the SDS score from Baseline to Week 12 will be analyzed using a MMRM model. 
The model will include randomized treatment group, SDS score at Baseline, week (as a discrete 
factor), treatment by week interaction, baseline by week interaction, and randomization stratum 
as fixed effects, and week as a repeated effect. An unstructured variance-covariance matrix will 
be used to model the correlation among repeated measurements. The modeling detail and SAS 
code are similar to Section 9.1.2.  
The SDS data will also be summarized by time point. 
9.2.6.4. 
Change in PCL-5 from Baseline to Weeks 1, 4, 8, and 12. 
The PCL-5 is a 20-item participant-reported questionnaire that assesses the 20 DSM-5 symptoms 
of PTSD. The PCL-5 score is derived from the 20 questions on PTSD symptoms. The questions 
are rated on a 5-point scale from 0 (Not at all) to 4 (Extremely). The PCL-5 score ranges from 0 
to 80 and is assessed at Baseline and end of Weeks 1, 4, 8, and 12. The PCL-5 past week version 
is administered at end of Week 1 and the PCL-5 past month version is administered at Baseline 
and end of Weeks 4, 8, and 12.  
The change in participant and clinician-reported symptoms of PTSD as assessed by the PCL-5 
score from Baseline to Weeks 1, 4, 8, and 12, will be analyzed using MMRM. The model will 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
43 
 
 
  
 
include randomized treatment group, corresponding score at Baseline, week (as a discrete 
factor), treatment by week interaction, baseline by week interaction, and randomization stratum 
as fixed effects, and week as a repeated effect. An unstructured variance-covariance matrix will 
be used to model the correlation among repeated measurements. The modeling detail and SAS 
code are similar to Section 9.1.2.  
9.2.6.5. 
Change in PGI-S and CGI-S from Baseline to Weeks 1, 4, and 8 
PGI-S and CGI-S are described in Section 9.2.1. 
The change in participant and clinician-reported symptoms of PTSD as assessed by the PGI-S 
and CGI-S score from Baseline to Weeks 1, 4, and 8, will be analyzed using MMRM, separately 
for PGI-S, and CGI-S. The model will include randomized treatment group, corresponding score 
at Baseline, week (as a discrete factor), treatment by week interaction, baseline by week 
interaction, and randomization stratum as fixed effects, and week as a repeated effect. An 
unstructured variance-covariance matrix will be used to model the correlation among repeated 
measurements. The modeling detail and SAS code are similar to Section 9.1.2.  
9.2.6.6. 
Change in ISI and PSQI (with the PSQI-addendum) from Baseline to Week 12 
The ISI is a 7-item participant-reported questionnaire assessing the nature, severity, and impact 
of insomnia in the past month. The ISI score is derived from the 7 questions that are rated on a 5-
point scale from 0 to 4. Higher score indicates more severe sleep difficulties. The ISI score 
ranges from 0 to 28 and is assessed at Baseline and end of Weeks 1, 4, 8, and 12. 
The PSQI (with the PSQI-addendum; PSQI-A) is a participant-report questionnaire evaluating 
sleep quality and sleep disturbance. The PSQI (with the PSQI-A) is comprised of 2 sections, (a) 
the core PSQI and (b) the PTSD specific addendum. The core PSQI consists of 19-items and the 
addendum is comprised of an additional 7 items that are commonly reported by adults with 
PTSD (e.g., hot flashes, memories or nightmares of the traumatic experience, and episodes of 
terror during sleep) (Germain et al 2004). The PSQI (with the PSQI-A) yields the following 
scores: 7 component scores, a global score, and a PSQI-A total score. The PSQI (with the PSQI-
A) scores are calculated as outlined in Appendix 1. The PSQI (with PSQI-A) is assessed at 
Baseline and end of Weeks 1, 4, 8, and 12. The PSQI (with PSQI-A) past week version is 
administered at end of Week 1 and the PSQI (with the PSQI-A) past month version is 
administered at Baseline and end of Weeks 4, 8, and 12. 
The change in participant-reported sleep problems as measured by the ISI, PSQI (with the PSQI-
A) from Baseline to Week 12 will be analyzed using an MMRM model, separately for ISI, PSQI 
global score and PSQI-A total score. The model will include randomized treatment group, 
corresponding score at Baseline, week (as a discrete factor), treatment by week interaction, 
baseline by week interaction, and randomization stratum as fixed effects, and week as a repeated 
effect. An unstructured variance-covariance matrix will be used to model the correlation among 
repeated measurements. The modeling detail and SAS code are similar to Section 9.1.2. 
The ISI, PSQI (with PSQI-A) data will also be summarized by time point. For the PSQI (with 
PSQI-A) descriptive statistics for the 7 component scores will be provided time point.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
44 
 
 
  
 
9.2.6.7. 
Change in CAPS-5 Subscales from Baseline  
The 4 CAPS-5 subscales are described in Section 9.1.1.  
Change in PTSD symptom clusters (intrusive symptoms, avoidance symptoms, arousal/reactivity 
symptoms, and negative alterations in mood and cognition) as assessed by the change in the 4 
CAPS-5 subscale scores from Baseline to Weeks 4 and 12, will be analyzed using an MMRM 
model, for each of the subscales separately. 
The model will include randomized treatment group, corresponding CAPS-5 subscale score at 
Baseline, week (as a discrete factor), treatment by week interaction, baseline by week 
interaction, and randomization stratum as fixed effects, and week as a repeated effect. An 
unstructured variance-covariance matrix will be used to model the correlation among repeated 
measurements. The modeling detail and SAS code are similar to Section 9.1.2. 
9.2.6.8. 
Change in PHQ-9 from Baseline to Weeks 1, 4, 12 and change in SIGH-A from 
Baseline to Weeks 4, 8, 12 
The PHQ-9 is a component of the longer Patient Health Questionnaire and is a participant-
reported tool for assessing depression in the last 2 weeks. The PHQ-9 score is derived from the 9 
questions that are rated on a 4-point scale from 0 (Not at all) to 3 (Nearly every day). The PHQ-9 
score ranges from 0 to 27 and is assessed at Baseline and end of Weeks 1, 4, and 12.  
The SIGH-A is a 14-item clinician administered rating scale developed to measure the severity 
of anxiety symptoms in the past week or since last visit. The SIGH-A score is derived from the 
14 items that are rated on a 5-point scale from 0 (Absent) to 4 (Very severe). The SIGH-A score 
ranges from 0 to 56 and is assessed at Baseline and end of Weeks 4, 8, and 12. The SIGH-A 
baseline version is administered at Baseline and the SIGH-A since last visit version is 
administered at end of Weeks 4, 8, and 12.  
Change in mood and anxiety as assessed by the change in the PHQ-9 total score from Baseline to 
Weeks 1, 4, 12 and the change in the SIGH-A total score from Baseline to Weeks 4, 8 and 12, 
will be analyzed using an MMRM model, separately for PHQ-9 and SIGH-A. The model will 
include randomized treatment group, corresponding score at Baseline, week (as a discrete 
factor), treatment by week interaction, baseline by week interaction, and randomization stratum 
as fixed effects, and week as a repeated effect. An unstructured variance-covariance matrix will 
be used to model the correlation among repeated measurements. The modeling detail and SAS 
code are similar to Section 9.1.2. 
9.2.6.9. 
Change in ReQoL from Baseline to Week 12 
The ReQoL-10 is a 10-item participant reported outcome that has been developed to assess the 
quality of life for people with different mental health conditions in the past week. The ReQoL-10 
score is derived from the 10 items that are rated on a 5-point scale from 0 to 4. Higher scores 
indicate better quality of life. The ReQoL-10 score ranges from 0 to 40 and is assessed at 
Baseline and end of Week 12.  
Change in quality of life as assessed by the ReQoL-10 score from Baseline to Week 12 will be 
analyzed using an ANCOVA model. The model will include randomized treatment group, 
randomization stratum, and ReQoL-10 score at Baseline as covariates. The modeling detail and 
SAS code are similar to Section 9.2.6.3. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
45 
 
 
  
 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
46 
 
 
  
 
10. 
SAFETY  
Safety data will be primarily summarized by treatment group and pooled JZP150 treatment 
group using the Safety Analysis Set. Summaries of exposure data, AEs, SAEs, laboratory 
assessments, vital signs, physical examination, and concomitant medications will be presented. 
Data listings will also be presented for all safety endpoints. 
10.1. 
Exposure 
10.1.1. 
Extent of Exposure 
The exposure information will be summarized by treatment group with the Safety Analysis Set 
and by randomized treatment group with the Full Analysis Set 2 and PK Analysis Set using 
descriptive statistics as well as counts and percentages, as appropriate. Exposure summaries are 
based on data collected by the study intervention administration eCRF and data captured in EDC. 
A listing of study intervention exposure will also be presented. 
Duration of exposure, in days, is calculated as: date of last dose of study intervention – date of 
first dose of study intervention + 1. Interruptions are not taken into account for the duration of 
exposure. 
10.1.2. 
Treatment Compliance 
Summary statistics for compliance to study intervention will be presented using descriptive 
statistics based on the Safety Analysis Set and Full Analysis Set 2 by treatment group. 
Compliance will also be summarized by category (<75%, ≥75% to ≤100%, >100% to ≤125%, 
and >125%). A listing of compliance will also be presented. 
Compliance will be calculated as the number of capsules consumed (data captured in IRT) 
divided by the number of capsules that should have been consumed by the participant (data 
captured in EDC), expressed as a percentage i.e. 
𝑐𝑜𝑚𝑝𝑙𝑖𝑎𝑛𝑐𝑒(%) = 
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 𝑡ℎ𝑎𝑡 𝑠ℎ𝑜𝑢𝑙𝑑 ℎ𝑎𝑣𝑒 𝑏𝑒𝑒𝑛 𝑐𝑜𝑛𝑠𝑢𝑚𝑒𝑑 
10.2. 
Adverse Events 
Adverse events (AEs) occurring from the first dose of study intervention until the final study 
visit will be reported. If the Investigator becomes aware of an SAE within 14 days after the last 
dose of study intervention, the event must also be reported. In addition, any SAE assessed as 
related to study intervention or procedure by the Investigator must be reported regardless of time 
after study termination.  
Adverse events will be coded to SOC and PT using MedDRA, Version 24.0 or later. The 
investigator will assess the relationship of each AE to study intervention. An AE with a missing 
relationship to study intervention will be reported as related in the summaries. Severity, as 
determined by the Investigator, will be classed as mild, moderate, severe, life-threatening, or 
fatal.  
Note that participants who acquire COVID-19 or report AEs due to the COVID-19 public health 
emergency (e.g., anxiety) while on study will be coded accordingly and included in the treatment 
emergent adverse event (TEAE) summaries. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
47 
 
 
  
 
A TEAE is generally defined as any event with onset date on or after the first dose of study 
intervention, including AEs that occur until 14 days after the last dose date. Any AEs reported 14 
days after the last dose date will not be considered treatment emergent and will be included in 
the listing but not analyzed in the summaries.  
For the purpose of calculating treatment emergence, incomplete onset dates will be imputed as 
detailed in Appendix 2.  
For the summary of TEAEs in Safety Analysis Set by time of first onset, data will be 
summarized under the following categories: 
 Week 1 (Day 1 to 7). 
 Weeks 2 to 4 (Day 8 to 28). 
 Weeks 5 to 8 (Day 29 to 56). 
 Weeks 9 to 12 (Day 57 to 84). 
 After last dose. 
The time of first onset will be calculated for TEAEs as: 
Start date of TEAE – Date of first dose of study intervention + 1 day 
If patients have multiple occurrences of a TEAE then it will be counted once for the first 
occurrence only. For participants who discontinue study intervention prior to study completion, 
all TEAEs occurring after treatment discontinuation will be reported in the “After last dose” 
category.  
The time of first onset will also be used to assign TEAEs by study period onset as follows: 
 
Intervention Period (Day 1 to Day 84 for intervention completers or Day 1 to last dosing 
day for participants who discontinue intervention early)  
 
Safety Follow-up Period (> Day 84 for intervention completers or > last dosing day for 
participants who discontinue intervention early) 
If patients have multiple occurrences of a TEAE then it will be counted once for the first 
occurrence only. For participants who discontinue study intervention prior to study completion, 
TEAEs occurring after treatment discontinuation will be reported according to the time of first 
onset.  
Only TEAEs are included in summary tables unless otherwise specified. If a participant has 
multiple episodes of events coded to the same SOC or PT, then the participant will be counted 
just once in the summaries for that term. For summary tables, participant incidence of TEAEs by 
SOC and PT are sorted by descending order of frequency of SOC in the JZP150 4 mg treatment 
arm (then alphabetically for ties) and then by descending order of frequency of PTs within each 
SOC (then alphabetically for ties). For summaries by PT only, PTs will be sorted in descending 
order of frequency in the JZP150 4 mg treatment arm. Each TEAE will be summarized by 
treatment group and pooled JZP150 treatment groups. 
For the summary of TEAEs by maximal severity, for each participant, the worst severity 
recorded by PT and SOC will be used for summary purposes. If severity is missing, the severity 
level of “severe” will be assumed. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
48 
 
 
  
 
A general overall summary of TEAEs with the number and percent of participants who 
experienced the following types of events will be provided by treatment group and pooled 
JZP150 treatment groups: 
 Participants with any TEAE  
 Participants with any treatment-related TEAE  
 Participants with any serious TEAE  
 Participants with any treatment-related serious TEAE 
 Participants with TEAE by maximum severity  
 Participants with an AE outcome as death  
 Participants with any TEAE leading to study intervention discontinuation  
 Participants with any TEAE leading to study intervention dose interruption  
 Participants with at least one TEAE outcome 
Participant incidence of TEAEs by SOC and PT will be summarized by treatment group and 
pooled JZP150 treatment groups for the following:  
 TEAEs (by SOC and PT and PT only) 
 TEAEs reported in ≥2% of participants   
 Treatment-related TEAEs  
 Serious TEAEs 
 Treatment-related serious TEAEs 
 TEAEs by maximum severity  
 TEAEs leading to study intervention discontinuation 
 TEAEs of special interest (by category [defined in Section 10.2.1 and PT)  
 TEAEs leading to study intervention dose interruption 
 TEAEs by study period onset 
 TEAEs by time of first onset 
Separate AE listings will be provided including the following:  
 All AEs  
 AEs with an outcome of death  
 SAEs 
 AEs leading to permanent withdrawal of study intervention  
 Adverse events of special interest (defined in Section 10.2.1) 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
49 
 
 
  
 
10.2.1. 
Adverse Events of Special Interest  
TEAEs of special interest will be summarized by treatment group and pooled JZP150 treatment 
groups and may include the terms or categories noted below.  
 
Altered consciousness, such as somnolence and coma 
 
Cerebellar syndrome, such as limb ataxia, gait ataxia, postural ataxia, dysarthria, and 
nystagmus 
 
Other neurological symptoms, such as headache, dizziness, gait disturbance, slurred 
speech, blurred vision, amnesia 
The listing of PTs of special interest will be reviewed and finalized prior to each database 
extraction for analysis specified in Section 10.2.  
10.3. 
Laboratory Assessments 
The continuous clinical laboratory assessments (hematology, chemistry, urinalysis, 
 
) will be summarized in Safety Analysis Set using descriptive 
statistics by treatment group and pooled JZP150 treatment groups by scheduled visit.  
Change from baseline to each post-baseline visit for clinical laboratory values is (value at the 
post-baseline visit) – (baseline value). If the laboratory value is missing at either baseline or a 
specific post-baseline assessment for a participant, change between baseline and that assessment 
is unknown. 
Values for any of the clinical laboratory values parameters that are below or above the limit of 
quantification of the assay (BLQ or ALQ), will be summarized using the BLQ or ALQ threshold 
value; the actual reported value will be listed.  
Shift tables will summarize changes in clinical laboratory results by scheduled visit with respect 
to the Baseline result. Laboratory values are categorized into L1, low, normal, high, or H1 based 
on the laboratory reference range. L1 and H1 values are predefined per the laboratory vendor 
alert ranges and correspond to the extreme abnormal lower and higher ranges, respectively. 
Abnormal laboratory assessments deemed clinically significant by the investigator will be 
reported as an AE.  
A listing of participants with abnormal value(s) according to the following criteria will be 
provided using the Safety Analysis Set:  
 Any laboratory value that falls into the pre-defined low or high panic ranges (L1 or 
H1) per the ICON laboratory panic value chart.  
 Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3xUpper 
Limit of Normal (ULN) and total bilirubin > 2xULN  
 AST or ALT ≥ 5xULN,  
 Creatinine ≥ 176 μmol/L 
 Participants positive for alcohol, urine drug screen or pregnancy assessments  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
50 
 
 
  
 
All laboratory results, including pregnancy test, drug screen, and alcohol screen, will also be 
presented in participant data listings. 
10.3.1. 
Laboratory Normal Reference Ranges  
Quantitative laboratory measurements will be compared with the relevant laboratory reference 
ranges in SI units and categorized as:  
 Markedly abnormal low (Panic low values) 
 Low: Less than LLN and greater than Panic low 
 Normal: result within the laboratory normal reference range (LLN and ULN limit 
included)  
 High: greater than ULN and lower than Panic high values 
 Markedly abnormal high (Panic high values)  
Laboratory measurement panic values are included in Appendix 3 and Appendix 4. 
 
10.4. 
Vital Signs 
The following vital signs measurements will be reported for this study. 
 Systolic blood pressure (SBP), (millimeter of mercury [mmHg]) 
 Diastolic blood pressure (DBP) (mmHg) 
 Pulse (beats per minutes [bpm]) 
 Respiratory rate (breaths/min) 
 Temperature (°C) 
 Weight (kg) 
 Height (cm) 
 BMI (kg/m2) [derived as weight (in kg) / [height (in m)]2] 
These vital signs (with the exception of the BMI which will be calculated programmatically) will 
be measured during the Screening Visit and each in-clinic scheduled visit. Height (cm) will be 
obtained at Screening Visit only.  
The following summaries will be provided for vital signs data by treatment group and pooled 
JZP150 treatment groups by scheduled visit: 
 Observed and change from baseline by visit  
 Incidence of markedly abnormal criteria (as defined below) by visit  
10.4.1. 
Vital Signs Markedly Abnormal Criteria  
Markedly abnormal quantitative vital signs measurements will be identified in accordance with 
the following predefined markedly abnormal criteria as specified in Table 8. 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
51 
 
 
  
 
Table 8: 
Vital Signs Predefined Markedly Abnormal Criteria 
Variable (unit) 
Low 
High 
SBP (mmHg) 
≤ 90 mmHg AND  
change from baseline ≤ -20 mmHg 
≥ 180 mmHg AND 
change from baseline ≥ 20 mmHg 
DBP (mmHg) 
≤ 50 mmHg AND 
change from baseline ≤ -15 mmHg 
≥ 110 mmHg AND 
change from baseline ≥ 15 mmHg 
Pulse (bpm) 
≤ 50 bpm AND 
change from baseline ≤ -15 bpm 
≥ 120 bpm AND 
change from baseline ≥ 15 bpm 
Weight (kg) 
percentage change from baseline ≤ -10.0% percentage change from baseline ≥ 
10.0 % 
Temperature (ºC) 
≤ 35.0 ºC 
≥ 39.0 ºC 
Note: bpm: Beats per minute. DBP: Diastolic Blood Pressure. kg: kilogram. mmHg: Millimeter of mercury. SBP: 
Systolic Blood Pressure 
10.5. 
ECG 
A standard 12-Lead ECG will be recorded with the participant resting supine for at least 5 
minutes. Results from the central ECG core lab will be included in the reporting of this study. 
Triplicate ECGs will be measured at each specified visit, with repeat measures no more than 30 
minutes apart. Average values of available measures will be calculated for each visit. The 
following ECG parameters will be reported: 
 PR Interval (msec)  
 RR Interval (msec)  
 QRS Duration (msec)  
 QT Interval (msec)  
 QT Bazett’s correction (QTcB) Interval (msec) [derived]  
 QT Fridericia’s correction (QTcF) Interval (msec) [derived]  
 Mean HR (bpm)  
 Sinus Node Rhythms and Arrhythmias  
o Normal Sinus Rhythm  
o Sinus Arrhythmia  
o Sinus Tachycardia  
o Sinus Bradycardia  
 ECG Interpretation:  
o Normal  
o Abnormal  
 
The following summaries will be provided for ECG data by treatment group and pooled JZP150 
treatment groups by scheduled visit:  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
52 
 
 
  
 
 Observed and change from baseline by visit (for quantitative measurements)  
 ECG parameters results will be listed over time.  
10.5.1. 
ECG Specific Derivations 
𝑄𝑇𝑐𝐹(𝑚𝑠𝑒𝑐) = 
𝑄𝑇 (𝑚𝑠)
√𝑅𝑅(𝑚𝑠)/1000
3
 
𝑄𝑇𝑐𝐵 (𝑚𝑠𝑒𝑐) = 
𝑄𝑇 (𝑚𝑠)
√𝑅𝑅(𝑚𝑠)/1000
 
10.5.2. 
ECG Abnormal Criteria 
Abnormal quantitative ECG measurements will be identified in accordance with the following 
predefined markedly abnormal criteria (FDA 2005). 
Observed values for QT interval, QTcB interval and QTcF will be classified as follows at each 
time point: 
 > 450 msec (M) or 470 msec (F)  
 > 480 msec 
 > 500 msec 
Change from baseline for QT interval, QTcB interval and QTcF will be classified as follows: 
 >30 msec increase from baseline 
 >60 msec increase from baseline 
A listing of participants meeting markedly abnormal criteria as well as a listing of participants 
with abnormal ECG overall assessment will also be provided based on the Safety Analysis Set. 
10.6. 
Other Safety Endpoints 
10.6.1. 
Physical Examination 
A full PE will include, at a minimum, assessments of the cardiovascular, respiratory, 
gastrointestinal (including liver), neurological systems, 
 
). Newly observed clinically significant abnormalities or worsening of pre-existing findings 
after screening will be captured as an AE in the Adverse Event eCRF. 
 
 Any abnormalities 
identified at the screening PE should be recorded as medical history. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
53 
 
 
  
 
 For a specific body system, participants with both baseline and a post-baseline 
value will be included for shift summaries. For computing percentages, the denominator will be 
the number of participants with a baseline and a post-baseline value for the specific body system. 
10.6.2. 
Pregnancy testing 
Participants with confirmed positive test results of pregnancy based on urine sample (confirmed 
by serum sample) will be listed. 
10.6.3. 
Columbia-Suicide Severity Rating Scale  
The C-SSRS is a widely used measure of suicidal ideation and behavior. The instrument reliably 
predicts a potential suicide attempt in those who had previously attempted suicide and is able to 
determine clinically meaningful points at which a person may be at risk for an impending suicide 
attempt (Posner et al 2011). 
The following summaries will be provided for the C-SSRS data by scheduled visit and by 
treatment group and pooled JZP150 treatment groups: 
 Number and percentage of participants with any suicidal ideation (i.e., having responded 
yes to any of the 5 types of suicide ideation) as well as broken down by type of suicidal 
ideation  
 Number and percentage of participants with any suicidal behavior ((i.e., having 
responded yes to any of the 4 or 5 types of suicidal behavior, as applicable) as well as 
broken down by type of suicidal behavior  
 Number and percentage of participants with any suicidal behavior or any suicidal 
ideation; a participant having reported both suicidal behavior and suicidal ideation will be 
counted only once 
 Number and percentage of participants with self-injurious behavior without suicidal 
intent.  
Missing data will not be imputed. C-SSRS parameters will be summarized by scheduled visit. 
All C-SSRS parameters will be presented in the participant data listing. 
10.6.4. 
Marijuana Withdrawal Checklist 
The MWC is a 22-item measure developed to assess the incidence and severity of marijuana 
withdrawal symptoms during the past 2 weeks. The MWC score is derived from the 22 items that 
are each rated on a 4-point scale from 0 (none) to 3 (severe). The MWC score ranges from 0 to 
66 and is assessed at Baseline, end of Week 12, and safety follow-up visit.  
Observed and change from baseline values for the MWC score will be summarized by treatment 
group and pooled JZP150 treatment groups by scheduled visit.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
54 
 
 
  
 
11. 
PHARMACOKINETIC ANALYSES  
All study participants are required to provide blood samples for PK evaluation. The dosing 
regimen during the PK evaluation will be the participant’s currently assigned treatment regimen. 
Blood samples for measurement of plasma concentration of JZP150 and its metabolites will be 
collected at the protocol-specified time points. Blood samples of 4 mL will be drawn at predose 
and 1 sample at 2 (± 15 minutes) hours post dose on Week 1 and Week 12, 5 (± 15 minutes) and 
8 (± 15 minutes) hours post dose on Week 8.  
11.1. 
Pharmacokinetic Concentrations 
Descriptive statistics including number of participants, mean, SD, Min, median, Max, coefficient 
of variation (%CV), geometric mean, and geometric SD will be used to summarize the plasma 
concentration data of JZP150 and its metabolites including M21 and M22 by visit, time point and 
dose.  
All statistical summaries and displays will be based on scheduled sampling times unless there are 
significant deviations of actual sampling times from scheduled sampling times. In calculation of 
the plasma concentration summaries, if concentration values are below the limit of quantitation, 
they will be set to zero. 
Participants who are included in the PK summary but have missing data for a particular time 
point will not be included in the analysis for that time point. Unused data, measurements from 
excluded participants, unscheduled collections, or extra measurements will not be included in the 
summaries but will be presented in the participant data listings. 
Plasma concentrations of JZP150 and its metabolites, if applicable, will be listed by participant, 
dose, visit, and scheduled sampling time. Actual sampling times will be included in the listing. 
The exposure-response analysis may be conducted and reported separately. 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
55 
 
 
  
 
12. 
PHARMACODYNAMIC/BIOMARKER ANALYSES  
Pharmacodynamic markers (e.g., AEA concentration) will be measured and descriptive statistics 
including the number of participants, mean, SD, Min, median, Max, %CV, geometric mean, and 
geometric SD will be used to summarize AEA levels by visit and treatment group. The 
Pharmacodynamic Analysis Plan may be provided in a separate document.  
The pharmacodynamic-response analysis may be conducted and reported separately. 
13. 
PHARMACOGENOMIC ANALYSES  
Participation in pharmacogenomic sampling is optional. 
 analysis may be conducted 
and reported separately. The Pharmacogenomic Analysis Plan may be provided in a separate 
document.  
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
56 
 
 
  
 
REFERENCES 
1. Conover W and Iman RL. Analysis of Covariance Using the Rank Transformation. 
Biometrics. 1982; 38: 715-724. 
2. FDA, E14 Guidance for Industry. October 2005. E14 Clinical Evaluation of QT/QTc 
Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. 
3. Germain A, Hall M, Krakow B et al., A brief Sleep Scale for Posttraumatic Stress 
Disorder: Pittsburgh Sleep Quality Index Addendum for PTSD. Anxiety Disorders. 19 
(2005) 233–244 
4. Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. 1976. Rockville, 
MD, US Department of Health, Education, and Welfare. 
6. Hodges JL Jr., and Lehmann EL. Rank Methods for Combination of Independent 
Experiments in Analysis of Variance. Annals of Mathematical Statistics. 1962; 33:482–
497. 
7. Hodgins GE, Blommel JG, Dunlop BW, Iosifescu D, Mathew SJ, Neylan TC, Mayberg 
HS, Harvey PD. Placebo Effects Across Self-Report, Clinician Rating, and Objective 
Performance Tasks Among Women With Post-Traumatic Stress Disorder: Investigation 
of Placebo Response in a Pharmacological Treatment Study of Post-Traumatic Stress 
Disorder. J Clin Psychopharmacol. 2018 Jun;38(3):200-206. 
8. ICH Guideline: statistical principles for clinical trials. Technical report no. ICH/363/96, 
16 September 1998. Silver Spring: FDA. 
9. ICH (May 2021). E9(R1) STATISTICAL PRINCIPLES FOR CLINICAL TRIALS: 
ADDENDUM: ESTIMANDS AND SENSITIVITY ANALYSIS IN CLINICAL 
TRIALS. Guidance for Industry. US. Department of Health and Human Services Food 
and Drug Administration (Revision 1). 
10. Lu K, Mehrotra DV. Specification of covariance structure in longitudinal data analysis 
for randomized clinical trials. Stats Med, 29 (2010): 474-488. 
11. O’Kelly, M and Ratitch, B. 2014. Clinical Trial with Missing Data A Guide for 
Practitioners. 1st ed. West Sussex, UK: John Wiley & Sons. 
12. Rubin, D. B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: John 
Wiley & Sons. 
13. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo M et al. The 
Columbia–Suicide Severity Rating Scale: Initial Validity and Internal Consistency 
Findings from Three Multisite Studies with Adolescents and Adults. Am J Psychiatry. 
2011; 168: 1266-1277. 
14. Shapiro SS, Wilk MB. An Analysis of Variance Test for Normality (Complete Samples). 
Biometrica. 1965;52: 591-611. 
15. Stefanovics, E.A., Rosenheck, R.A., Jones, K.M., Huang, G. and Krystal, J.H., 2018. 
Minimal clinically important differences (MCID) in assessing outcomes of post-traumatic 
stress disorder. Psychiatric Quarterly, 89(1), pp.141-155. 1. 
16. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). 
Cochrane Database Syst Rev. 2006 Jan 25;2006(1). 
17. Weathers FW, Bovin MJ, Lee DJ, et al. The Clinician Administered PTSD Scale for 
DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans. 
Psychological Assessment. 2018;30(3):383.
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
57 
 
 
  
 
APPENDIX 1: PSQI (WITH PSQI-A) GLOBAL SCORE DERIVATION 
The PSQI contains 19 self-rated questions and 5 questions rated by a bed partner or roommate (if 
one is available). Only self-rated questions are included in the scoring of the PSQI global score. 
The 19 self-rated items are combined to form seven component scores: duration of sleep, sleep 
disturbance, sleep latency, day dysfunction due to sleepiness, sleep efficiency, overall sleep 
quality, and need meds to sleep. Each of the component scores has a range of 0-3 points. In all 
cases, a score of “0” indicates no difficulty, while a score of “3” indicates severe difficulty. The 
seven component scores are then added to yield the PSQI global score, with a range of 0-21 
(inclusive) points. A score of “0” indicates no difficulty and “21” indicates severe difficulties in 
all areas.  
The component scores are calculated as follows: 
 
Duration of Sleep: 
Score is calculated based on number of minutes entered in Question 4: During the past 
month/week, how many hours of actual sleep did you get at night? as follows: 
Value Provided 
Score 
≥ 7 hours of sleep (420 minutes) 
0 
≥ 6 hours of sleep (360 minutes) and < 7 hours of sleep (420 
minutes) 
1 
≥ 5 hours of sleep (300 minutes) and < 6 hours of sleep (360 
minutes) 
2 
< 5 hours of sleep (300 minutes) 
3 
 
This score will not be calculated if Question 4 is not answered. 
 
Sleep Disturbance: 
Score is calculated as a sum of the responses to Questions 5b) to 5j). Each question is rated on a 
4-point scale from 0 (not during the past month/week) to 3 (three or more times a week/three or 
more days in the past week) and the responses are summed to derive the component score.  
Sum of Scores 
Score 
0 
0 
1-9 
1 
10-18 
2 
19-27 
3 
 
This score will not be calculated if any of Questions 5b) to 5j) are not answered. 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
58 
 
 
  
 
 
Sleep Latency: 
Score is calculated as a sum of the responses to Question 2 and Question 5a). Score for Question 
2: During the past month/week, how long (in minutes) has it usually taken you to fall asleep each 
night? is calculated as follows: 
Value Provided 
Score 
0-15 minutes 
0 
16-30 minutes 
1 
31-60 minutes 
2 
61-600 minutes 
3 
 
Question 5a) is rated on a 4-point scale from 0 (not during the past month/week) to 3 (three or 
more times a week/three or more days in the past week). 
The responses to Question 2 and Question 5a) are summed to derive the component score.  
Sum of Scores 
Score 
0 
0 
1-2 
1 
3-4 
2 
5-6 
3 
 
This score will not be calculated if any of Question 2 and Question 5a) are not answered. 
 
Day Dysfunction due to Sleepiness: 
Score is calculated as a sum of the responses to Question 8 and Question 9.  Question 8 is rated 
on a 4-point scale from 0 (not during the past month/week) to 3 (three or more times a 
week/three or more days in the past week). Question 9 is rated on a 4-point scale from 0 (no 
problem at all) to 3 (a very big problem).  
The responses to Question 8 and 9 are summed to derive the component score.  
Sum of Scores 
Score 
0 
0 
1-2 
1 
3-4 
2 
5-6 
3 
 
This score will not be calculated if any of Questions 8 and 9 are not answered. 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
59 
 
 
  
 
Sleep Efficiency: 
Score is calculated using the responses to the following questions: 
1) Question 1: During the past month/week, what time have you usually gone to bed at 
night? 
2) Question 3: During the past month/week, what time have you usually gotten up in the 
morning? 
3) Question 4: During the past month/week, how many hours of actual sleep did you get at 
night? 
A temporary value is calculated to assess sleep efficiency as follows: 
1) If Question 3 > Question 1, Temp = [Question 4 (response in hours)/ (Question 3 (time) – 
Question 1 (time))] x 100% 
2) If Question 3 ≤ Question 1, Temp = [Question 4 (response in hours)/ (24 + Question 3 
(time) – Question 1 (time))] x 100% 
 
Depending on the Temp value, the component score is assigned as follows:  
 
Temp Value (%) 
Score 
≥ 85% 
0 
≥ 75% and < 85% 
1 
≥ 65% and < 75% 
2 
≥ 0% and < 65% 
3 
 
This score will not be calculated if any of Questions 8 and 9 are not answered. 
 
Overall Sleep Quality: 
Score is calculated based on the response to Question 6: During the past month/week, how would 
you rate your sleep quality overall? The response is rated on a 4-point scale from 0 (very good) 
to 3 (very bad). This score will not be calculated if Question 6 is not answered. 
 
Needs Meds to Sleep: 
Score is calculated based on the response to Question 7: During the past month/week, how often 
have you taken medicine to help you sleep (prescribed “over the counter”)? The response is rated 
on a 4-point scale from 0 (not during the past month/week) to 3 (three or more times a 
week/three or more days in the past week). This score will not be calculated if Question 7 is not 
answered. 
 
PSQI Global Score: 
The PSQI global score (total sleep quality score) is the sum of the 7 component scores: duration 
of sleep, sleep disturbance, sleep latency, day dysfunction due to sleepiness, sleep efficiency, 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
60 
 
 
  
 
overall sleep quality, and need meds to sleep. The range of the PSQI global score is from 0 to 21 
(inclusive). The global score will not be calculated if at least one score involved into the 
calculation has no value. 
 
PSQI Addendum Score:  
The PSQI-A total score is derived from a sum of the 7 sleep disturbance items that are 
commonly reported by adults with PTSD (e.g., hot flashes, memories or nightmares of the 
traumatic experience, and episodes of terror during sleep) (Germain et al 2004). Items which are 
rated on a 4-point scale from 0 (not during the past month/week) to 3 (three or more times a 
week). A PSQI-A total score is obtained from the sum of the 7-items and has a range of 0-21, 
with higher scores indicating worse sleep disturbance.  
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
61 
 
 
  
 
APPENDIX 2: DATE IMPUTATION RULES 
Incomplete Adverse Event Onset Date 
If year is missing (or completely missing): set to the date of first dose. 
If (year is present and month and day are missing) or (year and day are present and month 
is missing): 
 
If year = year of first dose: set the date to the first dose date. 
 
If year < year of first dose: set month and day to December 31st. 
 
If year > year of first dose: set month and day to January 1st. 
If month and year are present and day is missing: 
 
If year = year of first dose, and: 
If month = month of first dose: set day to day of first dose. 
 
 
If month < month of first dose: set day to last day of month. 
 
 
If month > month of first dose: set day to 1st day of month. 
 
If year < year of first dose: set day to last day of month. 
 
If year > year of first dose: set day to 1st day of month. 
             For all other cases: set to date of first dose. 
 
Incomplete Concomitant Medication Start Date 
If year is missing (or completely missing): do not impute. 
If (year is present and month and day are missing) or (year and day are present and month 
is missing): 
Set month and day to January 1st. 
If year and month are present and day is missing: 
Set day to 1st day of month. 
 
Incomplete Diagnosis or Symptom Onset Date 
If year is missing (or completely missing): do not impute. 
If (year is present and month and day are missing) or (year and day are present and month 
is missing): 
Set month and day to January 1st. 
If year and month are present and day is missing: 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
62 
 
 
  
 
Set day to 1st day of month 
Incomplete Concomitant Medication End Date 
Do not impute if Ongoing Flag is checked. 
If year is missing (or completely missing): do not impute. 
If (year is present and month and day are missing) or (year and day are present and month 
is missing): 
Set month and day to December 31st. 
If year and month are present and day is missing: 
Set day to last day of the month.  
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
63 
 
 
  
 
APPENDIX 3: ICON LABORATORY SERVICES (ILS) STANDARD ADULT PANIC VALUES 
TEST 
Conventional 
Units 
Reference 
Interval 
Panic 
Value 
< or = 
Panic 
Value 
> or = 
SI Units 
Reference 
Interval 
Panic 
Value 
< or = 
Panic 
Value 
> or = 
Glucose, Fasting 
Serum/Plasma 
mg/dL 
74-99 
40 (F) 
50 (M) 
400 
mmol/L 
4.10-5.50 
2.20 
(F) 
2.80 
(M) 
22.20 
Glucose, 
Random Serum 
mg/dL 
74-139 
40 (F) 
50 (M) 
400 
mmol/L 
4.10-7.74 
2.20 
(F) 
2.80 
(M) 
22.20 
Calcium 
mg/dL 
8.4-10.2 (F, >= 18 
yrs); 8.4-10.2 (M, 
18 yrs to <61 yrs); 
8.8-10.0 (M, >=61 
yrs) 
6.0 
14.0 
mmol/L 
2.10-2.55 (F, >= 
18 yrs); 2.10-2.55 
(M, 18 yrs to <61 
yrs); 2.20-2.50 (M, 
>=61 yrs) 
1.50 
3.50 
Adjusted 
Calcium 
mg/dL 
8.4-10.2 (F, >= 18 
yrs); 8.4-10.2 (M, 
18 yrs to <61 yrs); 
8.8-10.0 (M, >=61 
yrs) 
6.0 
14.0 
mmol/L 
2.10-2.55 (F, >= 
18 yrs); 2.10-2.55 
(M, 18 yrs to <61 
yrs); 2.20-2.50 (M, 
>=61 yrs) 
1.50 
3.50 
Potassium 
mmol/L 
3.5-5.1 
2.5 
6.5 
mmol/L 
3.5-5.1 
2.5 
6.5 
Total Bilirubin 
mg/dL 
Less than or = 1.20 
- 
3.33 
µmol/L 
Less than or = 20.5 
- 
57.0 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
64 
 
 
  
 
CK 
U/L 
29-168 (F) 
30-200 (M) 
- 
850 (F) 
975 
(M) 
U/L 
29-168 (F) 
30-200 (M) 
- 
850 (F) 
975 
(M) 
Platelets 
x 10^9/L 
15-400 
50 
1000 
x 
10^9/L 
15-400 
50 
1000 
Platelets, Na 
Citrate 
x 10^9/L 
131-362 
39 
914 
x 
10^9/L 
131-362 
39 
914 
WBC 
x 10^9/L 
3.50-11.10 
2.50 
30.00 
x 
10^9/L 
3.50-11.10 
2.50 
30.00 
HGB 
g/dL 
11.5-15.5 (F) 
13.2-17.0 (M) 
8.0 
18.0 
g/dL 
11.5-15.5 (F) 
13.2-17.0 (M) 
8.0 
18.0 
PT 
Sec 
11.8-14.7 
- 
25.0 
Sec 
11.8-14.7 
- 
25.0 
APTT 
Sec 
20.4-35.1 
- 
70.0 
Sec 
20.4-35.1 
- 
70.0 
INR 
Ratio 
0.8-1.1 
- 
5.0 
Ratio 
0.8-1.1 
- 
5.0 
HCG, 
Quantitative 
mIU/mL 
Less than or = 5.00 
(F) 
No Reference 
Range (M) 
- 
5.01 (F) 
IU/L 
Less than or = 5.00 
(F) 
No Reference 
Range (M) 
- 
5.01 (F) 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Jazz Pharmaceuticals 
 
 
{Statistical Analysis Plan - Protocol #}JZP150-201-02 
 
 
65 
 
 
  
 
APPENDIX 4: STUDY SPECIFIC CHANGES TO ILS STANDARD PANIC VALUES 
Test 
Reference Range 
Panic Value (≤) 
Panic Value (≥) 
Modified Panic 
Value (≤)  
Modified Panic 
Value (≥) 
Sodium 
(NAARCH) 
136 – 145 mmol/L 
No ICON Panic 
Value 
No ICON Panic 
Value 
< 130 mEq/L 
> 155 mEq/L 
Creatinine 
(CREATARCH)  
Male: 0.72 – 1.18 
mg/dL 
Female: 0.55 – 1.02 
mg/dL 
No ICON Panic 
Value 
No ICON Panic 
Value 
Use ICON Panic 
Value 
> 1.99 mg/dL 
ALT 
(ALTARCH) 
≤ 55 U/L  
No ICON Panic 
Value 
No ICON Panic 
Value 
Use ICON Panic 
Value 
> 165 U/L 
Triglycerides 
(TRIGARCH) 
< 150 mg/dL 
No ICON Panic 
Value 
No ICON Panic 
Value 
Use ICON Panic 
Value 
> 1000 mg/dL 
 
 
 
DocuSign Envelope ID: 76E8FE3A-697D-4258-B019-FC9862ECD6F0


Certificate Of Completion
Envelope Id: 76E8FE3A697D4258B019FC9862ECD6F0
Status: Completed
Subject: Complete with DocuSign: JZP150-201 SAP V1.0.pdf
Source Envelope: 
Document Pages: 65
Signatures: 3
Envelope Originator: 
Certificate Pages: 5
Initials: 0
AutoNav: Enabled
EnvelopeId Stamping: Enabled
Time Zone: (UTC-08:00) Pacific Time (US & Canada)
IP Address: 163.116.254.53 
Record Tracking
Status: Original
             12/12/2023 12:31:50 PM
Holder:
            
Location: DocuSign
Signer Events
Signature
Timestamp
Assoc Dir, Biostatistics
Jazz Pharmaceuticals
Security Level: Email, Account Authentication 
(Required)
Signature Adoption: Pre-selected Style
Signature ID: 
D9E0F8F4-AB96-44BC-8D6D-51F502953829
Using IP Address: 163.116.252.33
With Signing Authentication via DocuSign password
With Signing Reasons (on each tab): 
   I approve this GxP document
Sent: 12/12/2023 12:34:25 PM
Viewed: 12/12/2023 12:38:03 PM 
Signed: 12/12/2023 12:40:03 PM
Electronic Record and Signature Disclosure: 
      Accepted: 1/12/2021 11:07:18 AM
      ID: 2f944fd3-800d-4cbd-b0cb-24c7b13dcdd8
      Company Name: Jazz Pharmaceuticals
Sr Director, Statistics
Jazz Pharmaceuticals
Security Level: Email, Account Authentication 
(Required)
Signature Adoption: Pre-selected Style
Signature ID: 
F1EAA5F5-10C6-46C0-B57E-23057E8C651E
Using IP Address: 163.116.254.45
With Signing Authentication via DocuSign password
With Signing Reasons (on each tab): 
   I approve this GxP document
Sent: 12/12/2023 12:40:06 PM
Viewed: 12/12/2023 1:41:41 PM 
Signed: 12/12/2023 1:42:55 PM
Electronic Record and Signature Disclosure: 
      Accepted: 2/14/2020 1:06:36 PM
      ID: 67a3fd0d-7db0-46ed-b3b7-b7eb941ac397
      Company Name: Jazz Pharmaceuticals


Signer Events
Signature
Timestamp
Senior Director, Global Clinical Lead, Clinical 
Development Neuroscience
Jazz Pharmaceuticals
Security Level: Email, Account Authentication 
(Required)
Signature Adoption: Pre-selected Style
Signature ID: 
0B5CE5B0-7F4A-41E8-A231-89BDEA5C2B73
Using IP Address: 163.116.251.74
With Signing Authentication via DocuSign password
With Signing Reasons (on each tab): 
   I approve this GxP document
Sent: 12/12/2023 1:42:58 PM
Viewed: 12/12/2023 1:45:10 PM 
Signed: 12/12/2023 1:45:46 PM
Electronic Record and Signature Disclosure: 
      Accepted: 10/4/2021 9:33:01 AM
      ID: 935a8039-73fe-4bc0-a5c5-9420596ecf11
      Company Name: Jazz Pharmaceuticals
In Person Signer Events
Signature
Timestamp
Editor Delivery Events
Status
Timestamp
Agent Delivery Events
Status
Timestamp
Intermediary Delivery Events
Status
Timestamp
Certified Delivery Events
Status
Timestamp
Carbon Copy Events
Status
Timestamp
Witness Events
Signature
Timestamp
Notary Events
Signature
Timestamp
Envelope Summary Events
Status
Timestamps
Envelope Sent
Hashed/Encrypted
12/12/2023 12:34:25 PM
Certified Delivered
Security Checked
12/12/2023 1:45:10 PM
Signing Complete
Security Checked
12/12/2023 1:45:46 PM
Completed
Security Checked
12/12/2023 1:45:46 PM
Payment Events
Status
Timestamps
Electronic Record and Signature Disclosure


ELECTRONIC RECORD AND SIGNATURE DISCLOSURE 
From time to time, Jazz Pharmaceuticals (we, us or Company) may be required by law to provide 
to you certain written notices or disclosures. Described below are the terms and conditions for 
providing to you such notices and disclosures electronically through the DocuSign system. 
Please read the information below carefully and thoroughly, and if you can access this 
information electronically to your satisfaction and agree to this Electronic Record and Signature 
Disclosure (ERSD), please confirm your agreement by selecting the check-box next to ‘I agree to 
use electronic records and signatures’ before clicking ‘CONTINUE’ within the DocuSign 
system. 
 
Getting paper copies 
At any time, you may request from us a paper copy of any record provided or made available 
electronically to you by us. You will have the ability to download and print documents we send 
to you through the DocuSign system during and immediately after the signing session and, if you 
elect to create a DocuSign account, you may access the documents for a limited period of time 
(usually 30 days) after such documents are first sent to you. After such time, if you wish for us to 
send you paper copies of any such documents from our office to you, you will be charged a 
$5.00 per-page, with a minimum of $100 per-document fee. You may request delivery of such 
paper copies from us by following the procedure described below. 
 
Withdrawing your consent 
If you decide to receive notices and disclosures from us electronically, you may at any time 
change your mind and tell us that thereafter you want to receive required notices and disclosures 
only in paper format. How you must inform us of your decision to receive future notices and 
disclosure in paper format and withdraw your consent to receive notices and disclosures 
electronically is described below. 
 
Consequences of changing your mind 
If you elect to receive required notices and disclosures only in paper format, it will slow the 
speed at which we can complete certain steps in transactions with you and delivering services to 
you because we will need first to send the required notices or disclosures to you in paper format, 
and then wait until we receive back from you your acknowledgment of your receipt of such 
paper notices or disclosures. Further, you will no longer be able to use the DocuSign system to 
receive required notices and consents electronically from us or to sign electronically documents 
from us. 
 
All notices and disclosures will be sent to you electronically 
Electronic Record and Signature Disclosure created on: 8/8/2019 10:59:54 AM
Parties agreed to: 


Unless you tell us otherwise in accordance with the procedures described herein, we will provide 
electronically to you through the DocuSign system all required notices, disclosures, 
authorizations, acknowledgements, and other documents that are required to be provided or made 
available to you during the course of our relationship with you. To reduce the chance of you 
inadvertently not receiving any notice or disclosure, we prefer to provide all of the required 
notices and disclosures to you by the same method and to the same address that you have given 
us. Thus, you can receive all the disclosures and notices electronically or in paper format through 
the paper mail delivery system. If you do not agree with this process, please let us know as 
described below. Please also see the paragraph immediately above that describes the 
consequences of your electing not to receive delivery of the notices and disclosures 
electronically from us. 
 
How to contact Jazz Pharmaceuticals: 
You may contact us to let us know of your changes as to how we may contact you electronically, 
to request paper copies of certain information from us, and to withdraw your prior consent to 
receive notices and disclosures electronically as follows: 
To contact us by email send messages to: 
 
 
To advise Jazz Pharmaceuticals of your new email address 
To let us know of a change in your email address where we should send notices and disclosures 
electronically to you, you must send an email message to us at 
jazz_notices@jazzpharma.com and in the body of such request you must state: your previous 
email address, your new email address. 
If you created a DocuSign account, you may update it with your new email address through your 
account preferences. 
 
To request paper copies from Jazz Pharmaceuticals 
To request delivery from us of paper copies of the notices and disclosures previously provided 
by us to you electronically, you must send us an email to jazz_notices@jazzpharma.com and in 
the body of such request you must state your email address, full name, mailing address, and 
telephone number.  
 
To withdraw your consent with Jazz Pharmaceuticals 
To inform us that you no longer wish to receive future notices and disclosures in electronic 
format you may: 


i. decline to sign a document from within your signing session, and on the subsequent page, 
select the check-box indicating you wish to withdraw your consent, or you may; 
ii. send us an email to 
 and in the body of such request you must state 
your email, full name, mailing address, and telephone number. 
 
Required hardware and software 
The minimum system requirements for using the DocuSign system may change over time. The 
current system requirements are found here: https://support.docusign.com/guides/signer-guide-
signing-system-requirements. 
 
Acknowledging your access and consent to receive and sign documents electronically 
To confirm to us that you can access this information electronically, which will be similar to 
other electronic notices and disclosures that we will provide to you, please confirm that you have 
read this ERSD, and (i) that you are able to print on paper or electronically save this ERSD for 
your future reference and access; or (ii) that you are able to email this ERSD to an email address 
where you will be able to print on paper or save it for your future reference and access. Further, 
if you consent to receiving notices and disclosures exclusively in electronic format as described 
herein, then select the check-box next to ‘I agree to use electronic records and signatures’ before 
clicking ‘CONTINUE’ within the DocuSign system. 
By selecting the check-box next to ‘I agree to use electronic records and signatures’, you confirm 
that: 
 
You can access and read this Electronic Record and Signature Disclosure; and 
 
You can print on paper this Electronic Record and Signature Disclosure, or save or send 
this Electronic Record and Disclosure to a location where you can print it, for future 
reference and access; and 
 
Until or unless you notify Jazz Pharmaceuticals as described above, you consent to 
receive exclusively through electronic means all notices, disclosures, authorizations, 
acknowledgements, and other documents that are required to be provided or made 
available to you by Jazz Pharmaceuticals during the course of your relationship with Jazz 
Pharmaceuticals. 
 
You are the user identified and that you are applying to use electronic signatures at Jazz 
Pharmaceuticals. Your first and last names and assigned user name are correct. You 
hereby agree to use the combination of my assigned user name and associated private 
password as my electronic signature to review and approve documents that require my 
signature. You further agree that this electronic signature shall be the legally binding 
equivalent of my handwritten signature. You understand that you are accountable and 
responsible for any actions on documents that you initiate under your electronic 
signature.