Conditions: Atopic Dermatitis
Keywords: CBD Synthetic CBD Cannabidiol
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 200
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, vehicle-controlled, Phase 2 study in subjects with moderate AD.

Detailed description:
This is a randomized, double-blind, vehicle-controlled, Phase 2 study in subjects with moderate AD. Eligible subjects will be enrolled and randomized to treatment with BTX 1204 or Vehicle for 84 days. Approximately two hundred (200) subjects will be enrolled. Subjects will receive BID application of study drug for 84 days with a final application on the evening of Day 84 for a total of 168 doses.

Arms:
arm 1: BTX 1204 twice daily arm 2: Vehicle twice daily

Interventions: intervention 1: BTX 1204 intervention 2: Vehicle
Intervention descriptions: intervention 1: BTX 1204 liquid formulation intervention 2: Vehicle liquid formulation

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
 
Study Title:  
A Randomized, Double-Blind, Vehicle-Controlled Study of the 
Safety, Tolerability and Efficacy of BTX 1204 in Patients with 
Moderate Atopic Dermatitis 
 
Protocol Number: 
 
BTX.2018.003 
Version: 
 
 
1.0 
Phase:  
 
 
2a 
 
Sponsor: 
 
 
Botanix Pharmaceuticals Ltd 
 
 
 
 
68 Aberdeen Street  
Northbridge, WA 6003 
Australia 
 
 
Final Approval Date:  
21-AUG-2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document is confidential communication of Botanix Pharmaceuticals Ltd.  Acceptance of 
this document constitutes the agreement by the recipient that no unpublished information 
contained within will be published or disclosed without prior written approval, except that this 
document may be disclosed to the appropriate Institutional Review Board/Human Research 
Ethics Committee under the condition that they are requested to keep it confidential. 
NCT03824405


 
 
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PROTOCOL SIGNATURE PAGE – SPONSOR 
 
Study Title:  
A Randomized, Double-Blind, Vehicle-Controlled Study of the 
Safety, Tolerability and Efficacy of BTX 1204 in Patients with 
Moderate Atopic Dermatitis 
 
Protocol Number: 
BTX.2018.003 
 
Version: 
 
 
1.0  
 
Signature: 
 
The undersigned acknowledges that he/she has received and read Protocol BTX.2018.003, 
Version 1.0, dated 21-AUG-2018. 
 
Sponsor Representative 
Signature 
Date 
Mark Davis 
VP, Clinical and Regulatory 
Affairs  
 
 
 
 
 
 
 
 
 
 
21 August 2018


 
 
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PROTOCOL SIGNATURE PAGE – INVESTIGATOR 
 
Study Title:  
A Randomized, Double-Blind, Vehicle-Controlled Study of the 
Safety, Tolerability and Efficacy of BTX 1204 in Patients with 
Moderate Atopic Dermatitis 
 
Protocol Number: 
BTX.2018.003 
 
Version: 
 
 
1.0 DRAFT v0.9 
 
Signature: 
 
The undersigned acknowledges that he/she has received and read Protocol BTX.2018.003, 
Version 1.0, dated 21-AUG-2018. 
 
Principal Investigator 
Signature 
Date 
 
 
 
 
 
 
By signing this protocol, the investigator has agreed to conduct this study in accordance with the 
requirements of this clinical protocol and in accordance with established principles of current Good 
Clinical Practice (GCP), Title 21 of the Code of Federal Regulations sections 50, 56, and 812 as 
applicable, and the ethical principles that have their origin in the Declaration of Helsinki. 
 
 
 
 
 
 


 
 
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DOCUMENT REVISION HISTORY 
 
Date 
Summary of changes 
Version 1.0 
21-AUG-2018 
Original document  
 


 
 
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LIST OF ABBREVIATIONS 
AD 
Atopic Dermatitis 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BID 
Twice Daily 
CBC 
Complete Blood Count 
CBD 
Cannabidiol 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CMP 
Clinical Monitoring Plan 
CRA 
Clinical Research Assistant / Associate 
CRO 
Clinical Research Organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food & Drug Administration 
GCP 
Good Clinical Practices 
GMP 
Good Manufacturing Practices 
HREC 
Human Research Ethics Committee 
IB 
Investigator’s Brochure 
IND 
Investigational New Drug 
IGA 
Investigator’s Global Assessment 
IFN 
Interferon 
IL 
Interleukin 
IRB 
Institutional Review Board 
ITF 
Investigator’s Trial File 
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web-based Response System 
MCH 
Mean Corpuscular Haemoglobin 
MCHC 
Mean Corpuscular Haemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OTC 
Over the Counter 
PK 
Pharmacokinetics 
p.m. 
Post Meridiem 
PPG 
Polypropyleneglycol 
PPP 
Pharmaceutical Packaging Professionals 


 
 
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QA 
Quality Assurance 
QC 
Quality Control 
QD 
Once Daily 
RBC 
Red Blood Cell 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Event 
THC 
Tetrahydrocannabinol 
TMF 
Trial Master File 
UDS 
Urine Drug Screen 
UPT 
Urine Pregnancy Test 
vIGA-AD 
Validated Investigator Global Assessment scale for Atopic 
Dermatitis 
WBC 
White Blood Cell 
WHO 
World Health Organization 
WOCBP 
Women of Child-Bearing Potential 


 
 
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PROTOCOL SUMMARY 
Title: 
A Randomized, Double-Blind, Vehicle-Controlled Study of the 
Safety, Tolerability and Efficacy of BTX 1204 in Patients with 
Moderate Atopic Dermatitis 
Study Phase: 
2a 
Dose and Treatment 
Duration: 
There will be two dose groups.  All subjects will apply study drug for 
84 days. 
• BTX 1204 4% twice daily (BID), or 
• Vehicle BID 
Study Duration: 
There will be a total of up to 112 days; screening period (up to 28 days), 
and 84 days of treatment. 
Investigational 
Product: 
BTX 1204 Liquid Formulation 
Concurrent Control: 
BTX 1204 Vehicle 
Administration 
Route and Form:  
BTX 1204 4% (w/w) or Vehicle applied topically 
Objective: 
To determine the safety, tolerability and efficacy of BTX 1204 in 
subjects 12 to 70 years of age with moderate atopic dermatitis (AD).   
Study Design: 
This is a multi-center, randomized, double-blind, vehicle-controlled, 
parallel-group study. 
Outcome Measures: 
The efficacy of BTX 1204 4% (w/w) will be evaluated using the 
Validated Investigator Global Assessment scale for Atopic Dermatitis 
(vIGA-ADTM; heretofore – IGA), Body Surface Area (BSA) of AD, 
Signs of AD (erythema, exudation, excoriation, induration/papulation, 
and lichenification), and Eczema Area Severity Index (EASI) Scores 
completed by the treating dermatologist along with Itching-Numerical 
Rating Score (I-NRS) and Worst Itching NRS (WI-NRS) scores 
reported by subjects. At selected sites, a target lesion will be identified, 
photographed and scored with the Signs of AD. 


 
 
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The efficacy outcome measures are: 
Primary endpoint: 
The primary efficacy endpoint for the study is the proportion of subjects 
with IGA success defined as an IGA score of “Clear” (0) or “Almost 
Clear” (1) with at least a 2-grade improvement from Baseline at Day 85. 
Secondary endpoints:   
The secondary endpoints for the study are: 
• The proportion of subjects with an EASI 75 score at Day 85,  
• The proportion of subjects with an EASI 50 score at Day 85, 
• The change from Baseline in the Signs of AD score at Day 85, 
• The proportion of subjects with an IGA of Clear or Almost 
Clear at Day 85, 
• The proportion of subjects with at least a 2-grade improvement 
in ISGA from Baseline at Day 85, 
• The change from Baseline in the percent of BSA affected by 
AD at Day 85,  
• The time to achieve IGA success, and 
• The change from Baseline to Day 85 in the I-NRS  
Exploratory endpoints: 
The exploratory endpoints are: 
• The change from Baseline in the Signs of AD score at Day 15, 
Day 29, and Day 57, 
• The change from Baseline in the percent of BSA affected by 
AD at Day 15, Day 29, and Day 57,  
• The proportion of subjects with IGA success defined as an 
IGA score of “Clear” (0) or “Almost Clear” (1) with at least a 
2-grade improvement from Baseline at Day 15, Day 29, and 
Day 57,  
• The percent change from Baseline in the EASI Score at 
Day 85, 


 
 
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• Change from Baseline in the subject’s reports of pruritus 
obtained daily on a Patient Diary. 
• Time to improvement of pruritus (change of ≥ 4 in the Worst 
Itch Numerical Rating Score [WI-NRS, 0 – 10 score]),  
• Subject’s assessment of the change in their AD from Baseline 
to Day 85 (Patient Reported Outcome [PRO]), and  
• The change from Baseline to Day 29, and Day 57, and Day 85 
in the Signs of AD score for the target lesion (at selected sites 
only). 
The safety outcome measures to be assessed are: 
• Reported adverse events (AEs) including treatment-emergent 
(TEAE) monitored from time of consent through the end of 
study; 
• Changes in clinical labs including complete blood count (CBC), 
chemistry, and urinalysis between Baseline and Day 85, 
• Subject’s reports of burning/stinging obtained during visits on 
Day 1, Day 15, Day 29, Day 57, and Day 85. 
Pregnancy testing will be conducted for women of child-bearing 
potential (WOCBP) at the Screening Visit, the Baseline Visit (if > 7 
days from Screening Visit) and at the Day 29, Day 57 and Day 85 
Visits. 
Total Sample Size:  
Approximately 200 subjects randomized 1:1 (100 subjects to 
BTX 1204 4% and 100 subjects to Vehicle) will be enrolled.    
Methods: 
Subjects will begin screening to determine eligibility to participate in 
the study.  Informed consent/assent, medical history/review of systems, 
demographics, height and weight will be obtained.  Urine pregnancy 
testing (UPT) will be conducted for WOCBP and a urine drug screen 
(UDS) will occur. Measurement of the total body surface area (BSA) 
of AD involvement and IGA will be assessed at Screening.  At selected 
photography sites, a target lesion will be identified.  
Within 28 days after the Screening Visit, Baseline assessments for 
safety (CBC, chemistry, and urinalysis) will be obtained on Day 1.  If 
the subject is eligible to participate, Screening and Baseline may occur 
at the same visit. If the Screening Visit and Baseline Visit are not 
concurrent, IGA, UPT, UDS, and BSA of AD, will be repeated at the 


 
 
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Baseline Visit. Review of eligibility criteria will be repeated.  Signs of 
AD and the EASI scores will be obtained. Subjects will be asked to rate 
their pruritus using the itch numeric rating score (I-NRS) which is an 
average level of itch over the past 24 hours on a scale of 0 (no itch) to 
10 (worst imaginable itch).  At selected sites, photographs and Signs of 
AD scoring of the target lesion will be obtained.  Subjects will be 
randomized 1:1 using an Interactive Web-based Response System 
(IWRS) to receive active BTX 1204 4% or Vehicle.  Subjects will 
receive their first dose of study drug applied by the site staff and will 
be observed in the clinic for approximately 15 minutes after the initial 
application.  Subjects will be given 4 weeks of study drug and instructed 
in the proper application for twice daily (BID) applications to cover 
their AD lesions, except on the scalp and groin.   
Subjects will be provided with a diary to record their daily pruritus 
score using the worst itch numeric rating score (WI-NRS).  Subjects 
will record the WI-NRS over the past 24 hours each day prior to their 
morning application.  Subject will also record on the diary the time of 
their morning and evening applications of study drug.  
Subjects will return to the clinic on Day 15.  Subjects will be queried 
for adverse events and changes in concomitant medications since their 
previous visit.  Returned study drug will be weighed and diaries will be 
reviewed for compliance.  The site will obtain IGA, BSA of AD, Signs 
of AD score, EASI score.  Subjects will be asked to rate their pruritus 
using the I-NRS.  The subject will then apply their dose of study drug 
during the visit for the clinical site to confirm correct application 
techniques.         
Subjects will return to the clinic on Day 29 and Day 57.  Subjects will 
be queried for adverse events and changes in concomitant medications 
since their previous visit. A UPT will be done on WOCBP.  Returned 
study drug will be weighed and diaries will be reviewed for compliance. 
The site will obtain IGA, BSA of AD, Signs of AD, and EASI Score. 
Subjects will be asked to rate their pruritus using the I-NRS.  At 
selected sites, the target lesion will be photographed and scored with 
the Signs of AD score.  The subject will then apply their dose of study 
drug during the visit for the clinical site to confirm correct application 
techniques.  Another four weeks of study drug will be dispensed along 
with a new diary.       


 
 
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The final study drug application will be applied in the evening prior to 
the Day 85 Visit.   
Subjects will return to the clinic for their final visit on Day 85 for safety 
assessments; blood samples for CBC and chemistry, and urine samples 
for urinalysis.  A UPT will be conducted for WOCBP.  Subjects will be 
queried for adverse events and changes in concomitant medications 
since their previous visit.  Returned study drug will be weighed and 
diaries will be reviewed for compliance.  The site will obtain IGA, BSA 
of AD, Signs of AD score, and EASI Score. Subjects will be asked to 
rate their pruritus using the I-NRS. At selected sites, the target lesion 
will be photographed and scored with the Signs of AD score.   
If a subject discontinues from the study early, all Day 85 assessments 
will be completed.  
After completion of study assessments, the subject will be discharged 
from the study.  
  Statistical Methods 
All statistical processing will be performed using SAS® unless 
otherwise stated. 
Analysis Sets: 
This study will be evaluated using 3 analysis sets: intent-to-treat (ITT), 
per protocol (PP), and safety.  Efficacy conclusions will be drawn from 
the ITT analysis set.  The ITT analysis set will consist of all randomized 
subjects with at least one post-baseline efficacy assessment and will be 
based on randomized study group, regardless of study drug received.  
The PP analysis set will be used to support the efficacy findings in the 
ITT analyses and will include subjects with no major protocol 
deviations.  Safety conclusions will be drawn from the safety analysis 
set.  The safety analysis set will include all subjects that received at 
least one application of study drug and had at least one post-baseline 
safety assessment with treatment based on study drug received 
regardless of randomization group.   
Demographics will be summarized using the safety analysis set by 
baseline age, gender, race, ethnicity, height, weight, and BMI.  The 
primary efficacy analysis will be conducted on the ITT population.  For 
continuous variables, the mean, standard deviation (SD), median, and 
range will be presented along with the 95% confidence interval (CI).  


 
 
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Categorical variables will be summarized by proportions along with the 
95% CI. 
Handling of Missing Data: 
The primary method of handling missing efficacy data in the ITT 
analysis set will be based on LOCF.  Other imputation methods (e.g., 
mixed model for repeated measurement [MMRM]) may be used as a 
sensitivity analysis.  
All safety analyses will be conducted using the safety analysis set. No 
imputations will be made for missing safety data. 
Efficacy Analyses: 
The efficacy analyses will be performed using the ITT (primary) and 
PP (supportive) analysis sets. The efficacy variables include the IGA, 
BSA of AD, Signs of AD score, and EASI score collected at Screening 
and/or Baseline and all subsequent study visits. The primary efficacy 
endpoint for the study is the proportion of subjects with IGA success 
defined as an IGA score of Clear (0) or Almost Clear (1) with at least a 
2-grade improvement from Baseline at Day 85.  The IGA will be 
dichotomized into “success” and “failure” at study Day 15, Day 29, Day 
57, and Day 85.   
This Phase 2a study is designed to identify the response to BTX 1204 
relative to vehicle. Statistical tests applied to the outcomes will be 
exploratory.  No adjustments for Type 1 error will occur. 
Success on IGA defined as a score of Clear (0) or Almost Clear (1) and 
at least a 2-grade improvement from Baseline at Day 15, Day 29, Day 
57, and Day 85 will be analyzed using logistic regression, adjusting for 
Baseline IGA.   
The change from Baseline in BSA of AD at Day 15, Day 29, Day 57 
and Day 85 will be analyzed used ANCOVA with Baseline BSA of AD 
and treatment as covariates.  
Summary statistics will be presented for the change from Baseline in 
each of the Signs of AD (erythema, exudation, excoriation, 
induration/papulation, and lichenification) at each timepoint (Day 15, 
Day 29, Day 57 and Day 85).  A total score will be calculated based on 
the sum of each of the Signs of AD (0, 1, 2, or 3; max score of 15) and 
the change from Baseline will be summarized for each timepoint.  The 
change from Baseline in Signs of AD at Day 15, Day 29, Day 57, and 


 
 
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Day 85 will be analyzed using ANCOVA with Baseline Signs of AD 
score and treatment as covariates.   
Summary statistics will be prepared for the change from Baseline in the 
EASI Score and I-NRS at each timepoint (Day 15, Day 29, Day 57 and 
Day 85). Summary statistics will also be prepared for the change from 
Baseline in the Signs of AD score for the target lesion (selected sites) 
at each timepoint (Day 15, Day 29, Day 57 and Day 85).  
Summaries of the pruritus scores reported by the subjects in the daily 
Patient Diary will be presented using daily means by treatment and with 
graphic presentations.  
Safety Analyses:  
All subjects who receive at least one confirmed dose of study drug and 
have at least one post-Baseline assessment will be included in the safety 
analyses. Safety analyses will include summaries of AEs, TEAEs, 
serious AEs (SAEs), and changes in laboratory assessments.  AEs, 
TEAEs and SAEs will be coded using the MedDRA dictionary and 
summarized by treatment group, the number of subjects reporting 
events, system organ class, preferred term, severity, relationship to 
study drug, and seriousness. A list of subjects who prematurely 
discontinue from the study due to an AE and the reason for 
discontinuation will be provided. 
The number and percentage of subjects reporting each medication will 
be summarized.  Medications taken by each subject will be listed. 
Changes in laboratory parameters from Baseline to Day 85 will be 
summarized using shift tables to evaluate for trends.  Abnormal 
laboratory findings will be summarized and listed by subject. 
Concomitant medications will be mapped to ATC Level 2 using the 
WHODrug dictionary.  The number and percentage of subjects 
reporting each medication will be summarized.  Medications taken by 
each subject will be listed. 
Sample Size: 
The sample size for this study is based on clinical considerations only. 
Subjects will be randomized 1:1 with 100 subjects in each treatment 
group for a total 200 subjects. This is considered adequate to evaluate 
the safety and tolerability and preliminary information on efficacy of 


 
 
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twice daily BTX 1204 4% in the treatment of moderate atopic 
dermatitis in subjects aged 12-70.    


 
 
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SCHEMATIC OF STUDY DESIGN  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse events and concomitant medications monitored throughout the study 
Baseline Visit (Day 1) 
Safety labs, UPT, UDS, IGA, BSA of AD, signs of AD,  
EASI, I-NRS, photos (selected sites) 
Day 29 Visit (Day 29 ± 5 days) 
UPT, IGA, BSA of AD, signs of AD, EASI, I-NRS, compliance, 
photos (select sites) 
Day 15 Visit (Day 15 ± 3 days) 
IGA, BSA of AD, signs of AD, EASI, I-NRS, compliance,  
photos (select sites)  
Randomize 
Vehicle 
BID 
N=100 
BTX 1204 
4.0% BID 
N=100 
N = 200: Screening Visit (Day -28 to Day 1) 
Obtain consent/assent; Assess eligibility, obtain demographics, UPT 
Day 57 Visit (Day 57 ± 5 days) 
UPT, IGA, BSA of AD, signs of AD, EASI, I-NRS, compliance, 
photos (select sites) 
Day 85 Visit/EOS (Day 85 ± 5 days) 
Safety labs, UPT, IGA, BSA of AD, signs of AD, EASI, I-NRS 
photos (select sites) 


 
 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ......................................................................................................... 5 
PROTOCOL SUMMARY .............................................................................................................. 7 
SCHEMATIC OF STUDY DESIGN ........................................................................................... 15 
TABLE OF CONTENTS .............................................................................................................. 16 
1. 
INTRODUCTION: BACKGROUND AND SCIENTIFIC RATIONALE .......................... 20 
1.1. 
Background Information ................................................................................................ 20 
1.2. 
Rationale......................................................................................................................... 20 
1.2.1. 
Pathogenesis of Atopic Dermatitis.......................................................................... 20 
1.2.2. 
Rationale for the Development of BTX 1204 for the Treatment of Atopic Dermatitis
 
23 
1.2.3. 
BTX 1204 Nonclinical and Clinical Data ............................................................... 24 
1.3. 
Potential Risks and Benefits ........................................................................................... 26 
1.3.1. 
Known Potential Risks ............................................................................................ 26 
1.3.2. 
Known Potential Benefits ....................................................................................... 26 
2. 
OBJECTIVE ......................................................................................................................... 27 
3. 
STUDY DESIGN AND ENDPOINTS ................................................................................. 28 
3.1. 
Description of the Study Design .................................................................................... 28 
3.2. 
Study Endpoints ............................................................................................................. 28 
4. 
STUDY ENROLLMENT AND WITHDRAWAL .............................................................. 30 
4.1. 
Inclusion Criteria ............................................................................................................ 30 
4.2. 
Exclusion Criteria ........................................................................................................... 31 
4.3. 
Reasons for Withdrawal or Termination ........................................................................ 32 
4.4. 
Premature Termination or Suspension of Study ............................................................ 33 
5. 
STUDY DRUG ..................................................................................................................... 34 
5.1. 
Study Drug ..................................................................................................................... 34 
5.1.1. 
Acquisition .............................................................................................................. 34 
5.1.2. 
Formulations, Appearance, Packaging, and Labeling ............................................ 34 
5.1.3. 
Product Storage and Stability.................................................................................. 35 
5.1.4. 
Preparation .............................................................................................................. 35 
5.1.5. 
Dosing and Administration ..................................................................................... 35 


 
 
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5.1.6. 
Starting Dose ........................................................................................................... 36 
5.1.7. 
Dose Adjustments/Modifications/Delays ............................................................... 36 
5.1.8. 
Duration of Therapy ................................................................................................ 36 
5.1.9. 
Tracking of Dose..................................................................................................... 36 
5.2. 
Study Drug Accountability Procedures .......................................................................... 36 
6. 
STUDY PROCEDURES AND SCHEDULE ....................................................................... 37 
6.1. 
Study Specific Procedures/Evaluations .......................................................................... 37 
6.2. 
Laboratory Procedures/Evaluations ............................................................................... 40 
6.2.1. 
Clinical Laboratory Evaluations ............................................................................. 40 
6.2.2. 
Specimen Preparation, Handling, and Storage ....................................................... 41 
6.3. 
Study Schedule ............................................................................................................... 41 
6.3.1. 
Screening Visit ........................................................................................................ 41 
6.3.2. 
Baseline Visit .......................................................................................................... 42 
6.3.3. 
Study Drug Application Period ............................................................................... 43 
6.3.4. 
Day 15 Visit ............................................................................................................ 43 
6.3.5. 
Day 29 Visit ............................................................................................................ 43 
6.3.6. 
Day 57 Visit ............................................................................................................ 44 
6.3.7. 
Day 85 Visit/End of Study Visit ............................................................................. 45 
6.3.8. 
Early Termination Visit .......................................................................................... 45 
6.3.9. 
Schedule of Events Table ........................................................................................ 45 
6.4. 
Concomitant Medications, Treatment and Procedures .................................................. 47 
6.5. 
Prohibited Medication, Treatment, and Procedures ....................................................... 47 
6.6. 
Rescue Medication, Treatments and Procedures ............................................................ 48 
6.7. 
Subject Access to Study Agent at Study Closure ........................................................... 48 
7. 
ASSESSMENT OF SAFETY ............................................................................................... 49 
7.1. 
Specification of Safety Parameters ................................................................................ 49 
7.1.1. 
Definition of Adverse Events (AE)......................................................................... 49 
7.1.2. 
Definition of Serious Adverse Events (SAE) ......................................................... 49 
7.2. 
Classification of Adverse Events ................................................................................... 50 
7.2.1. 
Relationship to Study Drug ..................................................................................... 50 
7.2.2. 
Severity of Event..................................................................................................... 51 


 
 
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7.2.3. 
Expectedness ........................................................................................................... 51 
7.3. 
Time Period and Frequency for Event Assessment and Follow-up ............................... 51 
7.4. 
Reporting Procedures ..................................................................................................... 52 
7.4.1. 
Adverse Events Reporting ...................................................................................... 52 
7.4.2. 
Serious Adverse Event Reporting ........................................................................... 52 
7.4.3. 
Reporting of Pregnancy .......................................................................................... 53 
7.5. 
Safety Oversight ............................................................................................................. 53 
8. 
CLINICAL MONITORING ................................................................................................. 54 
9. 
STATISTICAL CONSIDERATIONS.................................................................................. 55 
9.1. 
Statistical and Analytical Plans ...................................................................................... 55 
9.2. 
Statistical Hypotheses .................................................................................................... 55 
9.3. 
Description of Statistical Methods ................................................................................. 55 
9.3.1. 
General Approach ................................................................................................... 55 
9.3.2. 
Safety Analyses ....................................................................................................... 55 
9.3.3. 
Efficacy Analyses ................................................................................................... 56 
9.3.4. 
Adherence and Retention Analyses ........................................................................ 57 
9.3.5. 
Baseline Descriptive Statistics ................................................................................ 57 
9.3.6. 
Planned Interim Analyses ....................................................................................... 57 
9.3.7. 
Multiple Comparison/Multiplicity .......................................................................... 57 
9.3.8. 
Handling of Missing Data ....................................................................................... 57 
9.3.9. 
Tabulation of Individual Response Data................................................................. 57 
9.4. 
Sample Size .................................................................................................................... 57 
9.5. 
Measures to Minimize Bias ............................................................................................ 58 
9.5.1. 
Enrollment/Randomization/Masking Procedures ................................................... 58 
9.5.2. 
Breaking the Study Blind/Subject Code ................................................................. 58 
10. 
QUALITY ASSURANCE AND QUALITY CONTROL ................................................. 59 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .... 60 
11.1. 
Regulatory, Ethical, and Study Oversight Considerations ......................................... 60 
11.1.1. 
Informed Consent/Assent Process ....................................................................... 60 
11.1.2. 
Institutional Review Board (IRB)/Ethics Committee (EC)................................. 60 
11.1.3. 
Subject and Data Confidentiality ........................................................................ 60 


 
 
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11.1.4. 
Research Use of Stored Human Samples, Specimens or Data ............................ 61 
11.1.5. 
Future Use of Stored Specimens ......................................................................... 61 
11.1.6. 
Key Roles and Study Administration .................................................................. 61 
12. 
DATA HANDLING AND RECORD KEEPING ............................................................. 63 
12.1.1. 
Data Handling and Record Keeping.................................................................... 63 
12.1.2. 
Protocol Deviations ............................................................................................. 64 
12.1.3. 
Publication and Data Sharing Policy ................................................................... 65 
12.2. 
Conflict of Interest Policy........................................................................................... 65 
13. 
LITERATURE REFERENCES ......................................................................................... 66 
APPENDIX A – CRITERIA OF HANNIFIN AND RAJKA ...................................................... 69 
 
TABLES 
Table 1  Potential Mechanisms of Cannabidiol as a Treatment for Atopic Dermatitis ................ 23 
Table 2 Validated Investigator Global Assessment scale for Atopic Dermatitis  (vIGA-ADTM) . 38 
Table 3  Signs of Atopic Dermatitis (Paller) ................................................................................ 39 
Table 4  Time and Events Schedule .............................................................................................. 46 
 
 
 


 
 
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1. INTRODUCTION: BACKGROUND AND SCIENTIFIC RATIONALE 
1.1. Background Information 
Botanix Pharmaceuticals' BTX 1204 contains the active pharmaceutical ingredient, cannabidiol 
(CBD; 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol).  CBD is 
a member of a broader family of compounds known as cannabinoids, a class of compounds 
originally derived from the cannabis sativa plant. [Olah 2014] CBD is chemically synthesized 
under Good Manufacture Practices (GMP) for use in this study. 
Interest in CBD-based therapeutics has increased significantly in recent years, as published data 
has highlighted the potential efficacy and safety benefits of this compound. [Volkow 2015] CBD 
is not psychoactive and clinical trials have demonstrated that CBD may successfully treat epilepsy, 
arthritis, pain, and even Fragile X Syndrome. [Fernandez-Ruiz 2012] There are now more than 
150 human clinical trials that have been completed, are underway, or pending recruitment around 
the world that are studying CBD in a range of diseases. [ClinicalTrials.gov Aug 2018] 
Botanix Pharmaceuticals is developing a number of topical formulations aimed at exploiting the 
potential immune regulatory and anti-inflammatory effects of CBD that have reported in the 
literature.  Initial clinical development of these topical formulations has focused on establishing 
the safety and local cutaneous tolerability when applied to the skin of healthy volunteers either as 
a single dose or as multiple doses.  Subsequent clinical studies have again focused on establishing 
safety and local cutaneous tolerability in the disease state under investigation.  To date, Botanix 
Pharmaceuticals has completed 3 Phase 1 clinical studies with formulations containing 
concentrations of CBD up to 5% (w/w) with once (QD) or twice daily (BID) dosage regimens for 
up to 28 days.  These formulations have been well-tolerated on normal skin and on skin displaying 
the underlying pathology of acne or atopic dermatitis (AD).  In the most recent study, 37 subjects 
with mild to moderate AD were treated with either vehicle or BTX 1204 4% (w/w) BID for 28 
consecutive days.  Evidence of a potential therapeutic benefit of BTX 1204 over vehicle was 
observed through at reduction in the Signs of AD scores from Baseline. 
This study is intended to establish safety, tolerability and efficacy in subjects with moderate AD 
treated BID with BTX 1204 4% (w/w) Liquid Formulation compared to subjects treated with 
Vehicle for 12 weeks. 
1.2. Rationale 
1.2.1. Pathogenesis of Atopic Dermatitis 
Atopic dermatitis is an inflammatory cutaneous disease which may co-exist with other 
immunoglobulin E (IgE)-dependent atopic diseases such as allergic rhinitis, bronchial asthma, and 
food allergy. [Nowicki 2015] The disease is a skin disorder which presents itself as itchy, inflamed, 
red, and possibly lichenified (i.e. thickened) skin with affected areas potentially distributed widely 
over the body. [National Eczema Organization, 2017]   The pathogenesis of the disease is thought 


 
 
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to involve an acute T-helper 2 (Th2) cell response followed by a chronic response involving 
additional T-helper populations; although more recent research suggests that Th2 cells and a more 
generalized T-cell response are present during both acute and chronic phases. [Gandhi 2017] The 
importance of Th2 cells and interleukin (IL)-4 and IL-13 signaling in the disease is supported by 
the effectiveness of dupilumab, a human monoclonal antibody specific to IL-4Rα that can block 
IL-4 and IL-13 signaling, to improve many symptoms of AD including pruritus, and reduction in 
AD area and severity. [Gandhi 2017]  
The classical steps of AD pathogenesis are the following (Figure 1): 
• A skin barrier defect or entry of a skin irritant triggers the release of IL-25, IL-33, and 
thymic stromal lymphopoietin (TSLP) from keratinocytes, which activate dendritic cells 
(antigen-presenting cells in the skin) and Langerhans cells. 
• During the “acute phase” of onset, dendritic cells cause excessive Th2, T-helper 22 
(Th22), and T-helper 17 (Th17) cell activation (note that these changes continue into the 
“chronic phase” of the disease).    
o Th2 cells produce IL-4, IL-13, and IL-31, which then induce changes in 
keratinocyte gene expression, disrupt skin barrier function, and trigger itch 
symptoms.  IL-4 and IL-14 can increase additional TSLP release from 
keratinocytes, which causes further Th2 cell activation.   
o Activated Th22 cells release IL-22 which promotes keratinocyte hyperplasia, 
downregulates keratinocyte differentiation, and synergizes with IL-17 to induce 
pro-inflammatory S100 genes.   
o Activated Th17 cells release IL-17 which can regulate S100 protein and gene 
expression.  
• During the chronic stage (day 3 onward), dendritic cells recruit T-helper 1 (Th1) cell 
populations via IL-12 and continue to recruit Th22 and Th17 cells.  Th1 cells release 
interferon-γ (IFN-γ), which may decrease the role of Th2 cells in the disease.  Th1, Th22, 
and Th17 cells induce responses that continue to attract additional immune cells to the 
epidermis, alter keratinocyte differentiation, and induce epidermal thickening.   


 
 
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Figure 1 
Pathogenesis of Atopic Dermatitis 
 
Figure 1 provides the various pathways involved in atopic dermatitis (from Guttman-Yassky 2017).  DC = dendritic 
cell; IFN-γ = interferon-γ; IL = interleukin; KC = keratinocyte; LC = Langerhans cell; Th = T-helper; TSLP = thymic 
stromal lymphopoietin 
 
It is estimated that Th2 cell response is dominant in ~80% of AD cases (extrinsic AD), but in other 
instances (intrinsic AD), there is a shift to a more pronounced Th22 and Th17 response. [D’Erme 
2017] A recent study suggests that IL-17 may have a more dominant role in AD than proposed in 
classical models [Tan 2017]: 
• Compared to healthy children, IL-17 protein levels were elevated in AD skin lesions, but 
not in the serum of children with AD, indicating that IL-17 acts locally.   
• The effects of 2,4-dinitrochlorobenzene (DNCB; used to induce a model of AD in mice) 
were evaluated in IL-17 knockout and in wild-type C57Bl/6 mice.  DNCB was able to 
induce AD-like lesions in both types of mice; however, epidermal and dermal thickness 
of the lesions in the IL-17 knockout mice were significantly decreased compared to what 
was observed in wild-type mice.   
• Skin mRNA levels of the Th2 cytokines IL-4 and IL-13 were decreased in IL-17 
knockout mice compared to wild-type mice; however, there was no difference in skin 
mRNA expression levels of IFN-γ.  Splenocytes isolated from naïve IL-17 knockout mice 
released less IL-4 following concanavalin A (ConA) stimulation (a model of T-cell 
activation) compared to splenocytes from treated wild-type mice. 
IL-17 has been shown to trigger a pro-inflammatory response in an immortalized human 
keratinocyte cell line (HaCaT cells).  The addition of IL-17 increased the release of pro-
inflammatory IL-6 and IL-8, but not IL-1β.  This suggests that IL-17 may play a key role in the 
immune response associated with AD. 


 
 
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1.2.2. Rationale for the Development of BTX 1204 for the Treatment of Atopic Dermatitis 
The published literature suggests that CBD can potentially address the underlying immunological 
pathways and inflammatory response associated with AD.  CBD has been shown to alter gene 
expression of antigen-primed T-cells to induce a state of anergy via the Erg2 pathway and induce 
gene expression changes that leads to decreased antigen recognition in B-cells in an autoimmune 
disease model with a predominant Th17 response. [Kozela 2015] This suggests that CBD was able 
to decrease primed T-cell activity and also inhibit subsequent B-cell response.  CBD also altered 
gene expression in gingival stem cells to reduce antigen expression, thereby decreasing the 
potential for these cells to initiate an autoimmune response (Libro 2016), which could also provide 
a rationale for the use of CBD as a possible therapy for GvHD. [Yeshurun 2015a, Yeshurun 2015b] 
CBD was also shown to suppress multiple T-cell populations and inhibit general T-cell activation.  
[Faubert Kaplan 2003, Ignatowska-Jankowska 2009] Numerous experimental models have 
indicated that CBD can decrease concentrations of pro-inflammatory mediators and also increase 
the release of anti-inflammatory cytokines (such as IL-10).  CBD has also been shown to directly 
inhibit inflammatory responses due to the addition of IL-17A or IFN-γ. [De Filippis 2011, Harvey 
2014] The potential for CBD to inhibit the effects of IFN-γ and/or decreasing IFN-γ levels could 
serve a dual purpose; lower levels of IFN-γ could translate to a decreased inflammatory response 
and improve skin barrier function by reducing IFN-γ-mediated inhibition of long-chain fatty acid 
ceramide production in the skin. [Tawada 2014] 
Importantly, the literature indicates that CBD can inhibit the migration, proliferation and cell 
maturation processes involved in Th17, Th1, and Th2 immune responses. [Kozela 2015, Kozela 
2016, Lee 2016] These are considered critical immune pathways involved in the pathophysiology 
of AD. [Guttman-Yassky 2017] CBD may have beneficial effects on AD due to direct antioxidant 
effects, and ability to improve antioxidant status in models of inflammation and autoimmune 
disease. [Ben Shabat 2006, Booz 2011, De Filippis 2011, Fouad 2011, Mukhopadhyay 2011, 
Fouad 2012, Giacoppo 2015, Lee 2016] Finally, CBD may also provide a therapeutic benefit for 
the treatment of AD by modulating the inflammatory response regulated by keratinocytes.  CBD 
inhibited the production of monocyte chemotactic protein-2 (MCP-2), IL-6, IL-8, and tumor 
necrosis factor-α in polyinosinic-polycytidylic acid stimulated human keratinocyte (HaCaT) cells. 
[Petrosino 2018]  CBD has also been shown to directly inhibit the proliferation of keratinocytes. 
[Wilkinson 2007].  The potential mechanisms for CBD activity in AD are listed in Table 1.  
Table 1  Potential Mechanisms of Cannabidiol as a Treatment for Atopic Dermatitis 
Atopic Dermatitis 
• 
Decrease differentiation and proliferation and activity of t-helper 1, 2, and 17 cells. 
• 
Decrease interferon-γ and IL-17 levels and downstream effects.  
• 
Decrease interferon-γ, which may have an inflammatory effect and improve ceramide 
production in the skin.  The latter may prevent deterioration of skin barrier function.  
• 
Decrease monocyte chemotactic protein-2 (MCP-2), IL-6, IL-8, and tumor necrosis factor-α. 
• 
Decrease keratinocyte proliferation. 
• 
Increase intracellular expression of antioxidants and decrease reactive oxygen species. 
 


 
 
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It should be noted that there were no publications evaluating the effects of CBD on AD in the 
clinic or in animal models of this disease.  Additionally, there were no publications identified that 
explored the effects of CBD on the Th22 cell pathway.  
While CBD did appear to have a consistent anti-inflammatory and autoimmune inhibitory effect 
in the identified publications, some caution is warranted when trying to evaluate the potential 
effects of CBD for AD based on data from different autoimmune inflammatory disease models, as 
the underlying cause of the diseases models could differ.  For example, CBD had definitive effects 
on inhibiting IL17 release, decreasing Th17 cell activity and gene expression activity in an in vitro 
model of autoimmune encephalitis; however, CBD did not have any effects on antigen-mediated 
TNF-α or INF-γ release in this same model. [Kozela 2013, Kozela 2015, Kozela 2016] Similarly, 
in a murine model of type 1 diabetes, CBD was reported to inhibit Th1-mediated autoimmunity, 
but shift an immune response towards Th2 immunity, which was considered beneficial for the 
disease. [Weiss 2008] It is unclear whether CBD would induce a shift in T-cell populations in AD.  
Although there were subtle differences in how specific pathways were affected by CBD in these 
models, overall, CBD did demonstrate notable effects on inhibiting autoimmune responses in the 
test systems evaluated. 
An additional consideration needs to be given to a specific mechanism of action for CBD.  While 
not thoroughly investigated in each case, many of these studies showed that the reported effects of 
CBD are likely to be independent of cannabinoid receptors (CB1 or CB2).  Additional receptors 
that could be involved with CBDs effects on immune response and inflammation could be 
peroxisome proliferator-activated receptors (PPARs), adenosine A2 receptors, or the transient 
receptor potential cation channel subfamily V1 (TRPV1).  [De Filippis 2011, Esposito 2011, 
Hegde 2011, Ribeiro 2012, Petrosino 2018] However, the involvement of specific receptors is 
likely different for each model of autoimmune inflammation.       
1.2.3. BTX 1204 Nonclinical and Clinical Data  
The safety of BTX 1204 is supported by information from the published literature and studies 
conducted by Botanix Pharmaceuticals.  Botanix Pharmaceuticals has conducted nonclinical and 
clinical studies with CBD and with CBD formulated in an almost identical siloxane-based 
formulation known as BTX 1503.  The only difference between these formulations is that BTX 
1503 contains a very small amount of polydimethylsiloxane (dimethicone) at 1.0% (w/w).  
Comparative in vitro biopharmaceutic studies have shown both formulations have comparable 
transdermal permeation rates and equivalent deposition into the epidermal and dermal skin layers.  
To date, Botanix Pharmaceuticals has performed a full battery of genotoxicity studies, an ocular 
irritation study, a single dose pharmacokinetic (PK) study in minipigs, a 28-day repeat-dose oral 
toxicology study in rats, 28-and 90-day dermal toxicology studies in minipigs, and a local lymph 
node assay (LLNA) that support the safety of BTX 1204.  In addition, nonclinical information on 
systemic exposure to CBD obtained from the published scientific literature on the efficacy and 
safety pharmacology, on PK and metabolism, and on toxicity support the safety of CBD. 


 
 
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The results from these studies along with a comprehensive review of the scientific literature has 
established the safety profile of CBD and supports the proposed clinical investigation 
(BTX.2018.003) with topical application of CBD to patients with AD.  Details on the observations 
from Botanix Pharmaceuticals’ studies and the extensive literature review can be found in the IB.   
In addition, to the nonclinical data, the safety and tolerability of BTX 1204 4% (w/w) was 
evaluated in subjects with mild to moderate AD (BTX.2017.004).  In this study, BTX 1204 4% 
(w/w) Solution or Vehicle was applied to a target AD lesion and surrounding skin BID (180 mg 
CBD/day) for 28 consecutive days.  
Safety was assessed through collection of AEs, laboratory findings (CBC, chemistry, and 
urinalysis), urine drug tests conducted to detect the presence of THC, signs of AD score on the 
target lesion (erythema, exudation, excoriation, induration/papulation, and lichenification), and 
cutaneous tolerability assessments. 
This study demonstrated that daily topical treatment of BTX 1204 4% (w/w) Solution BID was 
safe and well tolerated.  No early discontinuations occurred as a result of an AE.  There were no 
SAEs reported and the most common AEs were general disorders and administration site 
conditions including application site erythema, application site pruritus, and application site pain. 
In studies conducted with BTX 1503, a formulation similar to BTX 1204 but with a drug load of 
5% (w/w), facial dryness and facial itchiness were reported as possible effects of the study drug 
treatment in a healthy volunteer study (BTX.2017.001). In an acne study (BTX.2017.002), slight 
to moderate erythema was reported most frequently in cutaneous tolerability assessments.  
However, most subjects that reported erythema pre-or post-study drug application had erythema 
at Baseline and treatment with BTX 1503 did not exacerbate the erythema.  Only 1 subject had 
increased erythema from Baseline and this was reported at Day 35, seven days after their final 
application of study drug.  Slight scaling was reported in 2 subjects (9.5%), slight dryness was 
reported in 4 subjects (19.0%) and slight burning/stinging was reported in 5 subjects (23.4%).  
Only one positive cutaneous tolerability assessment (slight dryness) was reported at more than a 
single visit. 
There is adequate support for evaluating the use of BTX 1204 4% (w/w) Liquid Formulation in 
this clinical study based on the findings observed in nonclinical and clinical studies conducted by 
Botanix Pharmaceuticals and its active ingredient CBD along with the extensive published 
literature on the use of CBD in multiple settings.   


 
 
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1.3. Potential Risks and Benefits 
1.3.1. Known Potential Risks 
Based on studies conducted by Botanix Pharmaceuticals with BTX 1204 4% and similar CBD 
products, the potential risks associated with BTX 1204 include: 
• Ocular irritation 
• Local application site AE’s 
• Cutaneous reactions which may include erythema, dryness, scaling, and burning/stinging.   
In the current study, subjects will be allowed to use their usual moisturizers.  Subjects in this study 
will be given instructions on what to do if BTX 1204 liquid accidentally gets into the eyes via a 
provided “patient instruction” video.   
In the published scientific literature, the only target organ for toxicity that has been identified was 
the testes in rat and monkey studies.  It is uncertain if the reduction in spermatogenesis noted in 
these animal studies has a clinical correlate.  In addition, this finding was not observed in the 28-
day oral rat study or in the 28- or 90-day dermal minipig studies conducted with Botanix 
Pharmaceuticals’ BTX 1503.   
The other aspect of systemic exposure to CBD reported in the published scientific literature was 
the potential for competitive binding to CYP450 isozymes, indicating a potential for drug-drug 
interactions.  Given the limited systemic exposure observed in Botanix Pharmaceuticals’ healthy 
volunteer study, the potential for a drug-drug interaction is considered to be minimal. 
1.3.2. Known Potential Benefits 
This study is the second study in evaluating the use of BTX 1204 4% (w/w) in subjects with AD.  
The preliminary efficacy of BTX 1204 4% (w/w) was evaluated in a Phase 1b, randomized, 
double-blind, vehicle-controlled study.  After only 4 weeks of treatment, subjects receiving BTX 
1204 4% (w/w) had improvements in the Signs of AD score compared to treatment with Vehicle.    
A total of 34.8% of subjects receiving BTX 1204 had a ≥ 4-point improvement in the Signs of AD 
score compared to 18.2% of subjects receiving vehicle.  Improvement was observed primarily in 
erythema, exudation and lichenification.   
Based on the non-clinical and accumulating clinical data, there is evidence that treatment with 
BTX 1204 4% (w/w) in subjects with AD may lead to decreased inflammation which may lead to 
a decrease in the signs and symptoms associated with AD.  As with any new form of treatment, 
potential benefits are not guaranteed.   Results from this study will provide guidance for additional 
safety and efficacy studies in AD and potentially other target patient populations. 
   


 
 
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2. OBJECTIVE 
The objective of this study is to determine the safety, tolerability and efficacy of BTX 1204 4% 
(w/w) in subjects with moderate atopic dermatitis. 


 
 
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3. STUDY DESIGN AND ENDPOINTS 
3.1. Description of the Study Design 
This is a randomized, double-blind, vehicle-controlled, Phase 2a study in subjects with moderate 
AD.  Eligible subjects will be enrolled and randomized to treatment with BTX 1204 4% (w/w) or 
Vehicle for 84 days.  Approximately two hundred (200) subjects randomized 1:1 (100 active: 100 
vehicle) will be enrolled. 
3.2. Study Endpoints 
The primary endpoint for the study is the proportion of subjects with an Investigator’s Global 
Assessment (IGA) success defined as an IGA score of “Clear” (0) or “Almost Clear” (1) with at 
least a 2-grade improvement from Baseline at Day 85.  
The secondary endpoints for the study are:  
• The proportion of subjects with an EASI 75 score at Day 85,  
• The proportion of subjects with an EASI 50 score at Day 85, 
• The change from Baseline in the Signs of AD score at Day 85, 
• The proportion of subjects with an IGA of Clear or Almost Clear at Day 85, 
• The proportion of subjects with at least a 2-grade improvement in ISGA from Baseline at 
Day 85, 
• The change from Baseline in the percent of body surface area (BSA) affected by AD at 
Day 85,  
• The time to achieve IGA success, and 
• The change from Baseline to Day 85 in the Itch-Numerical Rating Scale (I-NRS)  
Exploratory analyses will be conducted for:  
• The change from Baseline in the Signs of Atopic Dermatitis score at Day 15, Day 29, and 
Day 57, 
• The change from Baseline in the percent of body surface area (BSA) affected by AD at 
Day 15, Day 29, and Day 57,  
• The proportion of subjects with IGA success defined as an IGA score of “Clear” (0) or 
“Almost Clear” (1) with at least a 2-grade improvement from Baseline at Day 15, Day 
29, and Day 57,  
• The absolute and percent change from Baseline in the Eczema Area Severity Index 
(EASI) score at Day 15, Day 29, Day 57, and Day 85, 


 
 
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• Change from Baseline in the subject’s reports of pruritus obtained daily on a Patient Diary, 
• Time to improvement of pruritus (change of ≥ 4 in the Worst Itch Numerical Rating 
Score [WI-NRS, 0 – 10 score]),  
• Subject’s assessment of the change in their AD from Baseline to Day 85 (Patient 
Reported Outcome [PRO]), and     
• The change from Baseline to Day 29, and Day 57, and Day 85 in the Signs of AD score 
for the target lesion (selected sites). 
Safety outcome measures to be assessed are:  
• Reported adverse events (AEs) including treatment-emergent (TEAE) monitored from 
time of consent through the end of study, 
• Changes in clinical labs including complete blood count (CBC), chemistry, and urinalysis 
between Baseline and Day 85, and  
• Subject’s reports of burning/stinging obtained during visits on Day 1, Day 15, Day 29, Day 
57, and Day 85. 
 
  


 
 
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4. STUDY ENROLLMENT AND WITHDRAWAL 
4.1. Inclusion Criteria  
To be included in the study, subjects must meet the following inclusion criteria. 
1. 
Subject is of either gender between 12 and 70 years of age, inclusive.  
2. 
Subject (or parent/legal guardian) has the ability and willingness to sign a written informed 
consent. 
3. 
Subject has a diagnosis of chronic (≥1 year), stable atopic dermatitis (AD) according to 
Hanifin and Rajka [Hannifin 1980] 
4. 
Subject has ≥ 5% and ≤ 30% body surface area (BSA) of AD involvement excluding the 
scalp and groin.  
5. 
Subject has an Investigator’s Global Assessment (IGA) score of moderate (3) atopic 
dermatitis on the 5-point IGA (0-4) scale. 
6. 
For selected photography sites, subject has a target lesion 25 to 200 cm2 in surface area on 
the trunk, upper extremities or lower extremities with a Baseline Signs of AD score of ≥ 6 
and ≤ 12.  
7. 
Subject is in good general health without clinically significant hematological, cardiac, 
respiratory, renal, endocrine, gastrointestinal, psychiatric, hepatic, or malignant disease, as 
determined by the investigator. 
8. 
Subject has suitable venous access for blood sampling. 
9. 
Subject is able and willing to complete the study and to comply with all study instructions 
and attend the necessary visits. 
10. 
Male subjects and their partners must agree and commit to use a barrier method of 
contraception throughout the study and for 90 days after last study drug application.  
11. 
A negative urine pregnancy test (UPT) result for all WOCBP at the Screening Visit and 
Baseline Visit.  A WOCBP is one who is not permanently sterilized or not postmenopausal.  
Postmenopausal is defined as 12 months with no menses without an alternative medical 
cause. 
12. 
Sexually active women must agree to use the following throughout the study and for 30 
days after last study drug application. WOCBP who are not sexually active at Baseline 
and become sexually active must identify a plan for contraception.   
a. 
One of these highly effective contraception methods 
i. 
Intrauterine device (IUD); hormonal (injections, implants, transdermal 
patch, vaginal ring; tubal ligation; partner vasectomy, OR 
b. 
Oral contraceptives WITH a barrier method (listed below), OR 
c. 
Two barrier forms of contraception (listed below) 
i. 
Male or female condom; diaphragm; cervical cap; contraceptive sponge. 
13. 
Males subjects must refrain from sperm donation during the study treatment period and 
until 90 days after last study drug application. 


 
 
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4.2. Exclusion Criteria  
If a subject meets any of the following exclusion criteria, they may not participate in the study. 
1. 
Female subject who is breast feeding, pregnant, or planning to become pregnant.  
2. 
Subject who has an IGA score of 2 (mild) or 4 (severe). 
3. 
Subject with history of known or suspected intolerance to the drug product excipients 
(hexamethyldisiloxane, polypropylene glycol (PPG) 15 stearyl ether, silicone gum, and 
isopropyl alcohol).   
4. 
Subject has any clinically significant active infection in the investigator’s opinion. This 
includes active impetigo at any AD lesion. 
5. 
Subject has known Hepatitis-B, Hepatitis-C, or HIV infection. 
6. 
Subject has excessive body or facial hair that would interfere with the evaluation of safety 
or with the diagnosis or assessment of AD.  
7. 
Subject has sunburns, unevenness in skin tones, tattoos, scars, excessive hair, freckles, 
birthmarks, moles, or other skin damage or abnormality that would result in the inability 
to evaluate the AD lesions. 
8. 
Subject has clinically significant or severe allergies that in the investigator’s opinion would 
interfere with participation in the study. 
9. 
Subject has known intolerability to topical treatments e.g., reports excessive 
burning/stinging or pain with use of topical treatments. 
10. 
Subject has an active or potentially recurring skin conditions(s) other than AD that in the 
investigator’s opinion would interfere with participation in the study. 
11. 
Subject has unstable AD consistent with a requirement for high-potency corticosteroids. 
12. 
Subject has used dupilumab (Dupixent) within 12 weeks prior to the Baseline Visit. 
13. 
Subject has used any biologic therapy, other than dupilumab, within 28 days prior to the 
Baseline Visit. 
14. 
Subject has used systemic (oral, IV or IM) corticosteroids within 28 days prior to the 
Baseline Visit.  Intra-articular injection for arthroses allowed.   
15. 
Subject has used topical anti-pruritics (e.g., PDE4 inhibitors) within 28 days prior to the 
Baseline Visit. 
16. 
If subject is taking oral antihistamines, subject has not been on a stable dose of oral 
antihistamines within 28 days prior to the Baseline visit.  
17. 
Subject has used phototherapy, tanning beds, or any other artificial light device within 28 
days prior to the Baseline Visit. 
18. 
Subject has used topical corticosteroids within 14 days prior to the Baseline Visit. 
19. 
Subject has used topical calcineurin inhibitors within 14 days prior to the Baseline Visit. 
20. 
Subjects has used barrier creams (e.g., Mimyx, Atopiclair), within 7 days prior to the 
Baseline Visit.  


 
 
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21. 
Subject has an underlying disease that requires the use of interfering topical or systemic 
therapy. 
22. 
Subject has other dermatological conditions that require the use of interfering topical or 
systemic therapy or that might interfere with study assessments such as, but not limited to, 
acne or rosacea. 
Note: Treatment with any of the medications noted in Exclusion 11 through 22 is prohibited 
throughout the study.  Use of bland emollients once daily to manage dry skin areas around, but 
not overlapping, the treatable AD involved areas is acceptable.  
23. 
Subject has a clinically relevant history or currently suffering from any disease or condition 
that, in the opinion of the investigator, may affect the evaluation of the study product or 
place the subject at undue risk or interfere with the subject’s participation in the study. 
This may include respiratory (including chronic unstable asthma requiring repetitive drug 
interventions or hospitalization), gastrointestinal, renal, hepatic, haematological, 
lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, 
immunological, or connective tissue diseases or disorders. Subjects with other 
dermatologic conditions, including genetic syndromes that have an eczematous dermatitis 
as a component of the disease (e.g., Netherton’s) are excluded. 
24. 
Subject has a clinically relevant history of or current evidence of abuse of alcohol or other 
drugs.  Subjects may be deemed eligible if the UDS identifies subject-reported, prescribed 
drugs or appropriate levels of alcohol, as determined by the investigator. 
25. 
Subject is currently using any medication that, in the opinion of the investigator, may affect 
the evaluation of the study product or place the subject at undue risk. 
26. 
Subject has participated in another investigational drug or device research study within 30 
days of the Screening Visit or five half-lives of the drug, whichever is longer. 
27. 
Any other reason that would make the subject, in the opinion of the Investigator or sponsor, 
unsuitable for the study. 
4.3. Reasons for Withdrawal or Termination 
If a subject is withdrawn from the study, the subject’s enrollment in the study will terminate and 
study drug application will be discontinued.  Efforts will be made to perform all assessments 
scheduled for the Day 85 Visit prior to subject withdrawal.  Subjects may be replaced after 
consultation with the sponsor. 
A subject may be withdrawn from further study participation under the following circumstances: 
• At the subject’s request. 
• Noncompliance with protocol by the subject as determined by the study site staff and 
investigator. 
• Adverse Event (decision to be removed from study made by either the investigator or 
subject). The investigator must notify the sponsor immediately if a subject is withdrawn 
because of an AE. 


 
 
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• Decision by the investigator or sponsor that termination is in the subject’s best medical 
interest or administrative decision for a reason other than that of an AE. 
• Lost to follow-up, as determined by failure to respond to at least 2 telephone calls followed 
by certified letter sent to the subject’s last known address. All attempts to contact the 
subject must be documented in the subject’s source documents. 
• Sponsor decision to halt the entire study. 
4.4. Premature Termination or Suspension of Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to the investigator.  If the study is prematurely terminated 
or suspended by the sponsor, the PI will promptly inform the Human Research Ethics Committee 
(HREC) or Institutional Review Board (IRB) and will provide the reason(s) for the termination or 
suspension.  
Circumstances that may warrant termination or suspension include, but are not limited to:  
• Determination of unexpected, significant, or unacceptable risk to subjects  
• Insufficient compliance with protocol requirements  
• Data that are not sufficiently complete and/or evaluable  
The study may resume once concerns about safety, protocol compliance, or data quality are 
addressed and satisfy the sponsor and HREC/IRB. 


 
 
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5. STUDY DRUG 
5.1. Study Drug  
5.1.1. Acquisition 
Study drug will be provided to the US study sites by The Coghlan Group (TCG) in Bastrop, Texas, 
USA and to the Australian sites by PCI Pharma Services (PCI) in Port Melbourne, Victoria, 
Australia.  Initial shipments will be made to supply the study sites prior to enrollment of the first 
subject. Additional supplies will be made available as needed based on subject enrollment.  
5.1.2. Formulations, Appearance, Packaging, and Labeling 
Botanix Pharmaceuticals’ BTX 1204 contains the active pharmaceutical ingredient, cannabidiol 
(CBD).  CBD is a member of a broader family of compounds known as cannabinoids, a class of 
compounds originally derived from the cannabis sativa plant. [Olah 2014]  CBD is chemically 
synthesized under Good Manufacturing Practices (GMP) for use in this study. 
BTX 1204 4% Liquid Formulation (active) is a clear to slightly yellow liquid solution with a 4% 
(w/w) concentration of CBD in a formulation of excipients, which have been used extensively in 
other topical products.  These excipients include hexamethyldisiloxane, silicone gum, 
polypropylene glycol (PPG) 15 stearyl ether, and isopropyl alcohol (IPA).  The solution spreads 
easily and quickly evaporates leaving the CBD on the skin.   
Each milliliter of the BTX 1204 4% (w/w) Liquid Formulation contains 30.0 mg of CBD.  The 
Vehicle will be identical to the BTX 1204 4% (w/w), but without the CBD.     
Study drug, active and vehicle, will be supplied in 125 mL multi-dose, metered pumps delivering 
0.5 mL per actuation.  Each pump will contain approximately 100 mL of study drug.  Each subject 
will apply up to 7 mL per dose.  This will require 14 actuations of the pump.  Each dose will cover 
all the subject’s AD lesions (except scalp and groin).   
Pumps for all groups will be labeled identically, except for kit number and bottle number, to 
maintain the blind.   
Study drug will be applied directly to the AD lesion and spread to cover the AD lesion and up to 
1 cm of the surrounding non-lesional skin.  For lesions that cannot be accessed for direct 
application, study drug will be pumped into the palm of one hand and applied to the AD lesions.  
Adequate study drug will be provided in kits for daily applications (BID) through 4 weeks 
(Day 28).  Prior to distribution, pumps will be weighed by clinical site staff and the weights 
recorded in the source documents and the eCRF.  When a subject is enrolled, the site will access 
the IWRS to receive a kit number for the first 28 days of dosing based on the IWRS randomization.   
At the Day 29 and Day 57 Visits, the site will access the IWRS to obtain the kit number for the 
following 28 days of dosing.  All distributed pumps will be returned by the subject at the Day 29, 
Day 57, and Day 85 Visits and weighed to monitor compliance and document doses delivered.   


 
 
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The study drug bottle may include the following information: 
Caution: New Drug--Limited by Federal (or United States) law to investigational use only. 
KEEP OUT OF REACH OF CHILDREN 
Drug Ingredient:  BTX 1204 or Vehicle 
Directions: Use in accordance with study drug application instructions. 
FOR TOPICAL APPLICATION ONLY.  
Protocol # BTX.2018.003 
Flammable.  Store between 15-30
oC. 
 
Bottle # ________ 
Kit # __________ 
Sponsor: Botanix Pharmaceuticals Ltd  
 
5.1.3. Product Storage and Stability 
The study drug will be stored at a controlled room temperature of 15°C to 30°C and should not be 
refrigerated.  Prior to dispensing to the subject, the study drug will be stored in a secured location 
with access only by authorized study personnel.  Study drug has been tested to ensure that there is 
adequate stability for the duration of the study.  Retest dates may be included on the carton 
labeling. 
5.1.4. Preparation 
No preparation of the study drug is required.   
5.1.5. Dosing and Administration 
Subjects will receive their initial application of study drug on Day 1 at the clinical sites 
administered by the clinical site staff.  When the subject is ready for study drug application, a 
pump is selected from the assigned study kit.  The clinical site staff will unlock the pump and apply 
the first dose of the study drug to the subject’s AD lesions.  Study drug will be applied to the 
lesions and up to 1 cm of surrounding non-lesional skin.  Study drug will not be applied to AD 
lesions located on the scalp and the groin. 
Subjects will be instructed in how to apply study drug.  After their first application in the clinic 
subjects will apply their study drug at home.  Each application of study drug will occur at the 
approximately the same time in the morning with the second application approximately 8 to 12 
hours later.  Subjects will apply study drug at the clinical site during the Day 15, Day 29, and 
Day 57 Visits.  A diary will be maintained documenting compliance with the self-administered 
applications.  All study drug pumps (used and unused) will be returned to the clinical site and 
weighed on the Day 29, Day 57, and Day 85 Visits. 
Study drug should not be applied to the eyes or mouth.  If study drug accidentally gets into the 
eyes, the subject should flush their eyes with clear, running water.  Subjects are to thoroughly wash 


 
 
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their hands after study drug application.  The study drug must not be handled by a family member 
or caregiver for study drug application. 
5.1.6. Starting Dose  
The dose for all subjects will be up to 7 mL applied BID to cover their AD lesions and surrounding 
skin, except on the scalp and the groin.  No escalation of dose will occur.     
5.1.7. Dose Adjustments/Modifications/Delays 
There are no pre-planned dose adjustments, modifications, or delays.   
5.1.8. Duration of Therapy 
Subjects will receive BID application of study drug for 84 days with a final application on the 
evening of Day 84 for a total of 168 doses.  If the Day 85 Visit is delayed, the subject should 
continue dosing through the evening before the scheduled Day 85 Visit. 
5.1.9. Tracking of Dose 
All subjects will be required to maintain a diary documenting each application of study drug.  The 
subject will record that they applied each study dose.  Subjects will return the study drug pumps 
(used and unused) at visits 29, 57, and 85.  The clinical site staff will review the diary and count 
and weigh used/unused pumps to ensure subject compliance with dosing.   
5.2. Study Drug Accountability Procedures 
At each study visit the clinical site will weigh each pump dispensed to the subject and returned 
from the subject to calculate the amount (grams) of study drug used.  The investigator will keep a 
current and accurate inventory of all clinical supplies received.  These records will be reviewed at 
each monitoring visit performed by the CRA per SOPs.  In case of drug accountabilities 
discrepancies (missing pump, lost pump or non-compliance cases in which more product was used 
compared to expected use), investigators should obtain more information and explanation from the 
subjects. 
  


 
 
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6. STUDY PROCEDURES AND SCHEDULE 
6.1. Study Specific Procedures/Evaluations 
At the Screening Visit (Visit 1), all subjects will review and sign an informed consent/assent form 
attesting to their knowledge of the study requirements, risks, and benefits.  The following study 
specific procedures will occur for all subjects at the Screening Visit: 
• Demographics, height and weight, and a medical history will be obtained by the principal 
investigator or designee.   
• A review of systems will be conducted by the principal investigator or designee. 
• All WOCBP will have a UPT conducted.  The test must be negative for the subject to be 
enrolled.  
• A urine drug screen (UDS) will be conducted to ensure that the subject is not taking drugs 
of abuse. 
• The total body surface area (BSA) of atopic dermatitis involvement will be obtained.  The 
BSA can be approximated using the Rule of 9s or the palm (1%) method.   
• An IGA will be conducted.  The subject must have an IGA score of moderate (3) (see 
Table 2).  
• The subjects will be queried for concomitant medications that they are currently taking.  
Concomitant medications include all prescribed and over the counter (OTC) medications 
and any supplements. 
• Eligibility criteria will be reviewed to determine if subjects may proceed to study 
enrollment.   
• At selected sites, a target lesion will be identified.  Photographs will be obtained of the 
target lesion and the target lesion will be scored used the Signs of AD scoring. 
If subjects are eligible upon screening, they may be enrolled into the study on the same day.   
At various visits throughout the study, the following will occur for all subjects to monitor the safety 
of the study drug treatment: 
• Blood draws will be conducted for CBC and chemistry analysis 
• Collection of urine will occur for a urinalysis 
• Signs of AD score will be assessed (See Table 3). 
• Subjects will be queried to report any AEs that have occurred since the last visit.   
• Subjects will be queried to report any new medications or changes in current medications. 


 
 
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Efficacy will be assessed through collection of the IGA, Signs of AD score, BSA of AD, EASI 
score, and changes in pruritus.  An IGA will be conducted at Screening to ensure subject eligibility 
and again at Baseline (if not same day as Screening Visit) and Days 15, 29, 57 and 85.  The IGA 
assesses the overall status of the AD lesions at the time of the assessment.  Every effort should be 
made to have the IGA conducted by the same investigator/sub-investigator at each visit.  No 
comparisons are made to previous assessments.  The IGA is scored from 0 (Clear) to 4 (Severe) 
based on scoring system provided in Table 2.  
Table 2 Validated Investigator Global Assessment scale for Atopic Dermatitis  
(vIGA-ADTM)a  
Instructions: 
The IGA score is selected using the descriptors below that best describe the overall appearance of 
the lesions at a given time point.  It is not necessary that all characteristics under Morphological 
Description be present. 
Score 
Morphological Description 
0 – Clear  
No inflammatory signs of atopic dermatitis (no erythema, no induration/papulation, 
no lichenification, no oozing/crusting.  Post-inflammatory hyperpigmentation and/or 
hypopigmentation may be present. 
 
1 - Almost clear  Barely perceptible erythema, barely perceptible induration/papulation, and/or 
minimal lichenification. No oozing or crusting. 
 
2 – Mild  
Slight but definite erythema (pink), slight but definite induration/papulation, and/or 
slight but definite lichenification.  No oozing or crusting. 
 
3 – Moderate  
Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, 
and/or clearly perceptible lichenification.  Oozing and crusting may be present. 
 
4 – Severe  
Marked erythema (deep or bright red), marked induration/papulation, and/or marked 
lichenification.  Disease is widespread in extent.  Oozing or crusting may be present.   
 
 
Notes: 
1. In indeterminate cases, please use extent to differentiation between scores 
For example: 
• Patient with marked erythema (deep or bright red), marked papulation and/or 
marked lichenification that is limited in extent, will be considered “3 – Moderate”. 
2. Excoriations should not be considered when assessing disease severity.   
 
a Copyright ©2017 Eli Lilly and Company – Used with the permission of Eli Lilly and Company under a Creative 
Commons Attribution-NoDerivatives 4.0 International License – https://creativecommons.org/licenses/by-nd/4.0/ 


 
 
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The Signs of AD score will be an examination of all lesions on the subject for the presence of 
erythema, exudation, excoriation, induration/papulation, and lichenification.  Each sign will be 
graded according to the grade and definitions provided in Table 3. 
Table 3  Signs of Atopic Dermatitis (Paller) 
Score 
Grade 
Definition 
Erythema (redness) 
  0 
None 
No redness 
  1 
Mild 
Mildly detectable erythema; pink 
  2 
Moderate 
Dull red; clearly distinguishable 
  3 
Severe 
Deep, dark red; marked and extensive 
Exudation (oozing and crusting) 
  0 
None 
No oozing or crusting 
  1 
Mild 
Minor or faint signs of oozing 
  2 
Moderate 
Definite oozing or crusting 
  3 
Severe 
Marked and extensive oozing or crusting 
Excoriation (evidence of scratching) 
  0 
None 
No evidence of excoriation 
  1 
Mild 
Mild excoriation 
  2 
Moderate 
Definite excoriation 
  3 
Severe 
Marked, deep, or extensive excoriation 
Induration/papulation 
  0 
None 
None 
  1 
Mild 
Slightly perceptible elevation 
  2 
Moderate 
Clearly perceptible elevation but not extensive 
  3 
Severe 
Marked and extensive elevation 
Lichenification (epidermal thickening) 
  0 
None 
No epidermal thickening 
  1 
Mild 
Minor epidermal thickening 
  2 
Moderate 
Moderate epidermal thickening; accentuated skin lines 
  3 
Severe 
Severe epidermal thickening; deeply accentuated skin lines 
 
The EASI score will be conducted by the principal investigator or an appropriately trained 
designee to obtain a score to measure the extent (area) and severity of AD.  EASI will be scored 
using the area score for each of the four regions (head and neck, trunk, upper limbs, and lower 
limbs) of the body.  The area score is the percentage of skin affected by atopic dermatitis (eczema) 
for each body region:   


 
 
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Area score: Percentage of skin affected by eczema in each region 
0 
No active eczema in this region 
1 
1–9% 
2 
10–29% 
3 
30–49% 
4 
50–69% 
5 
70–89% 
6 
90–100%: the entire region is affected by eczema 
 
At each study visit, the subject will complete the Itch Numeric Rating Score (I-NRS).  
I-NRS 
The subject will be asked, “How would you rate your AVERAGE itch in the past 24 hours, on a 
scale from 0 to 10, where 0 is No itch and 10 is Worst itch imaginable?”  
Prior to morning application of the study drug, the subject will record in their diary the Worst Itch 
Numeric Rating Score (WI-NRS). 
Each day the subject will complete the Worst-Itch Numeric Rating Score (WI-NRS). 
WI-NRS 
The diary question will read, “How would you rate your WORST itch in the past 24 hours, on a 
scale from 0 to 10, where 0 is No itch and 10 is Worst itch imaginable?”  
For all subjects, assessment of compliance with study drug application will be conducted through 
collection of a study diary on which subjects will record their daily administration.  In addition, 
subjects will be required to return all used and unused study drug at each visit where the study site 
will assess compliance.  At each study visit the clinical site will weigh each pump dispensed to the 
subject and returned from the subject to calculate the amount of study drug used.   
6.2. Laboratory Procedures/Evaluations 
6.2.1. Clinical Laboratory Evaluations 
For all subjects, a CBC, chemistry, and urinalysis will be conducted at the Baseline and Day 85 
Visits.  If an abnormal laboratory assessment is returned from the Baseline assessments, 
consideration will be given by the investigator as to the continued participation of the subject in 
the study.  Details are provided in the Laboratory Manual.  Blood samples will be taken per 
standard venipuncture techniques.  The following will be assessed: 
CBC: White blood cell (WBC) count (with automated differential for absolute neutrophils, 
lymphocytes, monocytes, eosinophils, and basophils), red blood cell (RBC) count, 
haemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular 
haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and platelet 
count; 


 
 
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Chemistry: Glucose, albumin, total protein, calcium, sodium, potassium, chloride, CO2 
(bicarbonate), blood urea nitrogen (BUN), creatinine, alkaline phosphatase, alanine amino 
transferase (ALT), aspartate amine transferase (AST), and total bilirubin; 
Urinalysis: Color, clarity, specific gravity, pH, protein, glucose, and leukocyte esterase.  If 
the results are abnormal or further analysis is requested by the site, the sample will undergo 
microscopic analysis for red blood cells, white blood cells, and squamous epithelial cells. 
For all WOCBP, a UPT will be conducted at the Screening Visit, Baseline Visit (if >7 days from 
Screening Visit), and the Day 29, 57, and 85 Visits.  The assessment will be done using a test kit 
with a minimum sensitivity of 25 mIU/mL.  Details for collecting and testing urine for the UPT 
are provided in the Laboratory Manual.     
6.2.2. Specimen Preparation, Handling, and Storage 
Specimen preparation, handling, shipment, and storage for the CBC, chemistry and urinalysis are 
described in the Laboratory Manual.    
6.3. Study Schedule 
6.3.1. Screening Visit 
At the Screening Visit (Day -28 to Day 1), the following will be conducted: 
• Obtain written informed consent/assent 
• Conduct medical history and review of systems 
• Obtain subject’s demographics  
• Obtain subject’s height and weight 
• Conduct UPT (WOCBP only)  
• Collect urine sample for UDS 
• Perform IGA  
• Calculate BSA of total AD involvement 
• Identify a target lesion (selected photography sites only) 
• Review eligibility criteria 
• Query subject for concomitant medications 
If the subject is found to be eligible for participation in the study, the Baseline Visit procedures 
may then be conducted.  If the subject requires any washout period, this period must be completed 
prior to the Baseline Visit.  Subjects found to be ineligible will be screen failed and the reason for 
screen failure will be recorded.  Subjects that do not meet eligibility requirements (e.g. require 
washout from prohibited medications or have an active infection) may be re-screened once they 
meet eligibility requirements (e.g. washed out from the prohibited medication(s) or cleared an 
active infection). 


 
 
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6.3.2. Baseline Visit  
If the subject is deemed eligible and proceeds to enrollment on the same day, in addition to the 
screening assessments the following will be conducted: 
• Collect blood sample for CBC and chemistry 
• Collect urine sample for urinalysis  
• Assess Signs of AD prior to application of study drug 
• Collect EASI score prior to application of study drug 
• Collect I-NRS prior to application of study drug 
• Randomize subject to study drug treatment 
• Apply study drug on subject’s AD lesions (see Section 5.1.5) 
• Monitor subject for AEs 15 minutes after application of study drug 
• Photographs and Signs of AD scoring of target lesion (selected sites only) 
• Train subject in proper application of study drug 
• Weigh and dispense study drug 
• Dispense study diary (Day 1 through Day 28) and train the subject in entering 
administration times and daily pruritus score. 
If the subject is not enrolled on the same day as the Screening Visit, the following will be 
conducted at the Baseline Visit: 
• Review eligibility criteria 
• Review medical history and review of systems 
• Query subject for adverse events since the signing of the informed consent/assent and 
changes in concomitant medications  
• Collect blood sample for CBC and chemistry  
• Collect urine sample for urinalysis  
• Conduct UPT (WOCBP only) 
• Collect urine sample for UDS  
• Perform IGA prior to application of study drug 
• Calculate BSA of total AD involvement 
• Assess Signs of AD score prior to application of study drug 
• Collect EASI score prior to application of study drug 
• Collect I-NRS prior to application of study drug 
• Photographs and Signs of AD scoring of target lesion (selected sites only) 
• Randomize subject to study drug treatment 
• Apply study drug on subject’s AD lesions (see Section 5.1.5) 
• Monitor subject for AEs 15 minutes after application of study drug 
• Train subject in proper application of study drug  
• Weigh and dispense study drug 


 
 
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• Dispense study diary (Day 1 through Day 28) and train the subject in entering 
administration times and daily pruritus score. 
6.3.3.  Study Drug Application Period 
At the Day 1 Visit, the subject will receive their first study drug application at the clinical site 
during the Baseline Visit.  Subjects will be trained in the correct application of the study drug and 
provided an ample supply of study drug to complete BID dosing through Day 28. The first 
application of study drug will occur in the morning and the second application approximately 8 to 
12 hours later.  A diary will be maintained documenting compliance with application of the self-
administered application and daily pruritus score.  At the Day 29 Visit, the subject will be provided 
an ample supply of study drug to complete dosing through Day 56.  At the Day 57 Visit, the subject 
will be provided an ample supply of study drug to complete dosing through Day 84.  The final 
application of study drug will be applied by the subject on the evening of Day 84 or, if the Day 85 
Visit is delayed, the evening prior to the Day 85 Visit.   
6.3.4. Day 15 Visit 
The Day 15 Visit is conducted to ensure the continuing safety of the subject and to monitor 
compliance with the BID application of study drug.  Subjects will be instructed to not apply their 
morning application of study drug until they are seen in the clinic.  If the clinic visit is in the 
afternoon, the subject should apply their regular morning application and apply the evening 
application in the clinic, as long as the dose is at least 6 hours after the morning dose.  At the Day 
15 Visit (Day 15 ± 3 days) the following will be conducted.  
• Query subject for any AEs which have occurred since the last visit  
• Query subject for changes in concomitant medications  
• Perform IGA prior to application of study drug 
• Calculate BSA of total AD involvement 
• Assess Signs of AD score prior to application of study drug 
• Collect EASI score prior to application of study drug 
• Collect I-NRS prior to application of study drug 
• Photographs and Signs of AD scoring of target lesion (selected sites) 
• Have subject apply study drug on their AD lesions (see Section 5.1.5) 
• Review study diary and confirm compliance with study drug applications 
• Confirm compliance with study drug applications by weighing pumps 
6.3.5. Day 29 Visit 
Subjects will be instructed to not apply their morning application of study drug until they are seen 
in the clinic for the Day 29 Visit.  If the clinic visit is in the afternoon, the subject should apply 
their regular morning application and apply the evening application in the clinic, as long as the 


 
 
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dose is at least 6 hours after the morning dose.  At the Day 29 Visit (Day 29 ± 3 days) the following 
will be conducted.  
• Query subject for any AEs which have occurred since the last visit  
• Query subject for changes in concomitant medications  
• Conduct UPT (WOCBP only)  
• Perform IGA prior to application of study drug 
• Calculate BSA of total AD involvement 
• Assess Signs of AD prior to application of study drug 
• Collect EASI score prior to application of study drug 
• Collect I-NRS prior to application of study drug 
• Photographs and Signs of AD scoring of target lesion (selected sites only) 
• Have subject apply study drug on their AD lesions (see Section 5.1.5) 
• Collect study drug and study diary and confirm compliance with study drug applications 
by weighing returned pumps 
• Dispense study diary (Day 29 through Day 56) 
• Weigh and dispense study drug. 
6.3.6. Day 57 Visit 
Subjects will be instructed to not apply their morning application of study drug until they are seen 
in the clinic for the Day 57 Visit.  If the clinic visit is in the afternoon, the subject should apply 
their regular morning application and apply the evening application in the clinic, as long as the 
dose is at least 6 hours after the morning dose.  At the Day 57 Visit (Day 57 ± 5 days) the following 
will be conducted:  
• Query subject for any AEs which have occurred since the last visit  
• Query subject for changes in concomitant medications  
• Conduct UPT (WOCBP only)  
• Perform IGA prior to application of study drug 
• Calculate BSA of total AD involvement 
• Assess Signs of AD score prior to application of study drug 
• Collect EASI score 
• Collect I-NRS 
• Photographs and Signs of AD scoring of target lesion (selected sites only) 
• Have subject apply study drug on their AD lesions (see Section 5.1.5) 
• Collect study drug and study diary and confirm compliance with study drug applications 
by weighing returned pumps 
• Dispense study diary (Day 57 through Day 84) 
• Weigh and dispense study drug. 


 
 
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6.3.7. Day 85 Visit/End of Study Visit 
The final application of study drug will occur on the evening prior to the Day 85 Visit.  If the 
Day 85 visit is delayed, the subject should continue BID application until the evening before the 
Day 85 Visit.   At the Day 85 Visit (Day 85 ± 5 days), the following will be conducted: 
• Collect and weigh returned study drug pumps  
• Collect study diary 
• Query subject for adverse events that occurred since the previous visit  
• Query subject for changes in concomitant medications  
• Collect blood sample for CBC and chemistry  
• Collect urine sample for urinalysis  
• Conduct UPT (WOCBP only)  
• Perform IGA  
• Calculate BSA of total AD involvement 
• Assess Signs of AD score 
• Collect EASI score  
• Collect I-NRS 
• Photographs and Signs of AD scoring of target lesion (selected sites only) 
• Discharge subject from study 
6.3.8. Early Termination Visit 
If a subject terminates the study early for reasons other than an AE, attempts will be made to 
complete the assessments required for the Day 85 Visit.   
6.3.9. Schedule of Events Table  
The Schedule of Events is provided in Table 4. 


 
 
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Table 4  Time and Events Schedule  
Parameter 
 
Screening Visita 
(-28 to Day 1) 
Baseline Visit 
(Day 1) 
Day 15 Visit 
(Day 15 ±3 day) 
Day 29 Visit  
(Day 29 ±3 days) 
Day 57 Visit 
(Day 57 ±5 days) 
Day 85 Visitb 
(Day 85 ±5 days) 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Written informed consent/assent 
X 
 
 
 
 
 
Medical history/ Review of systems 
X 
Xa 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Height and weight measurement 
X 
 
 
 
 
 
Urine pregnancy test (WOCBP only) 
X 
Xa 
 
X 
X 
X 
Urine drug screen 
X 
Xa 
 
 
 
 
Eligibility criteria review 
X 
Xa 
 
 
 
 
IGA 
X 
Xa 
X 
X 
X 
X 
Body Surface Area (BSA) of AD 
X 
Xa 
X 
X 
X 
X 
Signs of AD score 
 
X 
X 
X 
X 
X 
EASI score 
 
X 
X 
X 
X 
X 
Pruritus Score (I-NRS) 
 
X 
X 
X 
X 
X 
Laboratory blood draw (CBC and chemistry) 
 
X 
 
 
 
X 
Urine collection for urinalysis    
 
X 
 
 
 
X 
Photographs and Signs of AD scoring of target 
lesion (selected sites) 
 
X 
X 
X 
X 
X 
Randomize subject 
 
X 
 
 
 
 
Study drug administration in clinic 
 
X 
X 
X 
X 
 
Study drug administration at home 
 
Day 1 pm to Day 84 pm; final application prior to Day 85 Visit 
Concomitant medications query 
X 
Xa 
X 
X 
X 
X 
Adverse experience query 
 
X 
X 
X 
X 
X 
Weigh and Dispense study drug 
 
X 
 
X 
X 
 
Collect and Weigh study drug 
 
 
Xc 
X 
X 
X 
Dispense Diary  
 
X 
 
X 
X 
 
Collect Diary and review compliance 
 
 
Xc 
X 
X 
X 
a  If subject meets eligibility criteria, Screening and Baseline Visit can occur on the same day.  If Screening and Baseline Visit are not concurrent, review of eligibility, Review of  
Systems, UPT, UDS, BSA of AD, IGA, and concomitant medications query will be repeated at the Baseline Visit. 
b  If subject discontinues treatment early, Day 85 evaluations will be performed when possible. 
c On Day 15, review compliance only.


 
 
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6.4. Concomitant Medications, Treatment and Procedures 
All concomitant medications taken during study participation will be recorded on the case report 
forms (eCRFs). For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be reported in the 
eCRF are concomitant prescription medications, OTC medications, and non-prescription 
medications.  In addition, vitamins, supplements and other non-pharmaceuticals products that are 
taken orally are to be reported in the eCRF.  Any use of marijuana containing products will be 
reported. 
Subjects will use their normal soaps or body washes throughout the study.  Changes in soaps and 
body washes during the study should not occur.  Subjects will be instructed to wash their body 
prior to the Baseline, Day 15, Day 29, and Day 57 Visits.  The body should not be washed within 
5 minutes prior to, or within 1 hour after application of study drug.  Subjects must agree to maintain 
their regular use of sunscreens and moisturizers throughout the entire course of the study.    
Detailed dosing instructions will be provided to the subject. 
6.5. Prohibited Medication, Treatment, and Procedures 
The following medications, treatments, and procedures are prohibited for all subjects during the 
study.   
• Treatable AD lesions cannot be washed or shaven within 5 minutes prior to or for 1 hour 
after application of study medication.  
• Participation in a clinical study of any investigational product or procedure. 
• Use of high dose (> 10,000 IU) Vitamin D.   
• Use of systemic corticosteroids (inhaled or intranasal corticosteroid ≤ 1000 µg daily dose 
is acceptable), oral antibiotics, or anti-inflammatory drugs (occasional NSAIDs to treat 
ailments are permitted)  
• Use of any topical agent, other than study drug, to treat AD.   
• Use of any oral medication for the treatment of AD. 
• Use of any medication that, in the opinion of the investigator, may affect the evaluation of 
the study product or place the subject at undue risk. 
• Use of topical or oral antibiotics.  If a subject gets an infection during the study that requires 
topical or oral antibiotics, the subject can be treated and allowed to remain on the study.  
The antibiotic use will be noted as a deviation.   
• Photodynamic therapy.  
• Use of tanning beds. 


 
 
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Subjects may use bland emollients to manage dry skin areas around, but not overlapping, the 
treatable AD lesions.  Sunscreens may be applied to the skin areas around, but not overlapping, 
the treatable AD lesions. 
Subjects should limit exposure of the treatment area to sunlight during the study.  Suitable clothing 
and other protective garments should be worn throughout the study. 
Subjects must not shower or wash the study application area for 1 hour after application of study 
drug.  Subjects should avoid swimming and heavy exercise for 1 hour after application of study 
drug.  
Subjects will wash their hands directly after application of study drug.   
6.6. Rescue Medication, Treatments and Procedures 
Systemic medications for treatment of AD are prohibited (see Section 6.5).  If a subject is unable 
to continue the study without additional treatment for the lesion areas, or if they require systemic 
treatment, the appropriate treatment should be administered.  Exacerbation of AD will be recorded 
as an AE.  The site will notify the study monitor immediately if this occurs.  The subject’s 
continuation on the study will be decided on a case-by-case basis. 
6.7. Subject Access to Study Agent at Study Closure 
Subjects will not have access to the study drug after completion of their participation until the 
product is available commercially. 


 
 
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7. ASSESSMENT OF SAFETY 
7.1. Specification of Safety Parameters 
7.1.1. Definition of Adverse Events (AE) 
An AE is defined as any untoward medical occurrence in a study subject which does not 
necessarily have to have a causal relationship with the study treatment.  An AE can therefore be 
any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of study drug treatment, whether or not considered 
related to the study drug.   
Any events involving illnesses or injuries with onset during the study or any events involving 
exacerbations of pre-existing illnesses should be recorded.  All clearly related signs and symptoms 
should be grouped together and recorded as a single diagnosis in the eCRF.  A pre-existing 
condition will not be reported as an AE unless the condition worsens during the trial.  The 
condition, however, must be reported in the Medical History section of the eCRF. Scheduled or 
planned diagnostic and therapeutic procedures such as surgery will not be reported as AEs.   
7.1.2. Definition of Serious Adverse Events (SAE) 
Each AE will be independently judged by the investigator in terms of seriousness.  A serious AE 
(SAE) is defined as any untoward medical occurrence that: 
• Results in death,  
• Is life-threatening, 
Note: The term “life-threatening” in the definition of “serious” refers to an event in which 
the subject 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. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, 
• Results in permanent impairment of a body function or permanent damage to a body 
structure,  
• Is a congenital anomaly/birth defect,  
• Necessitates medical or surgical intervention to preclude any one of the outcomes listed in 
this definition. 


 
 
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7.2. Classification of Adverse Events 
7.2.1. Relationship to Study Drug 
The investigator will review each event and assess its relationship (unrelated, unlikely, possibly, 
probably, definitely) to drug treatment.  The following definitions will be used for these causality 
assessments. 
Unrelated 
• The AE must clearly be caused by the subject’s clinical state, or the 
study procedure/conditions. 
• Definitely not related to drug. 
• Temporal sequence of an AE onset relative to administration of drug 
not reasonable. 
• Another obvious cause of an AE. 
Unlikely 
• Time sequence is unreasonable. 
• There is another more likely cause for an AE. 
Possibly 
• Corresponds to what is known about the drug. 
• Time sequence is reasonable. 
• Could have been due to another equally, likely cause. 
Probably 
• Is a known effect of the drug. 
• Time sequence from taking drug is reasonable. 
• Ceases on stopping the drug. 
• Cannot be reasonably explained by the known characteristics of the 
subject’s clinical state. 
Definitely 
• Is a known effect of the drug (e.g., listed in IB). 
• Time sequence from taking drug is reasonable. 
• Event stops upon stopping drug, event returns upon restarting drug. 
NOTE: Re-challenge will only be considered after consultation with 
the medical monitor and the sponsor. 
 


 
 
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7.2.2. Severity of Event 
Each sign or symptom reported will be graded on a 5-point severity scale (Grade 1, 2, 3, 4 and 5).  
The following definitions for rating severity will be used: 
Grade 1 
 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
Grade 2 
 
Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living.* 
Grade 3  
 
Severe or medically significant but not immediately life-threatening; 
Hospitalisation or prolongation of hospitalisation indicated; disabling; 
limiting self-care activities of daily living.** 
Note: An experience may be severe but may not be serious, (e.g., severe 
headache). 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
Note:  A semi-colon indicates ‘or’ within the description of the grade. 
*Instrumental activities of daily living refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc. 
**Self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
7.2.3. Expectedness 
For this study, all AEs will be recorded.   
The safety and tolerability of BTX 1204 4% (w/w) Solution was evaluated in a Phase 1b study in 
subjects with mild to moderate atopic dermatitis.  This study demonstrated that BTX 1204 4% was 
safe and well tolerated with up to 3 mL applied BID for up to 28 days.  Adverse events reported 
as related to study drug treatments were administration site conditions including application site 
erythema, application site pruritus, and application site pain. 
Studies of the active ingredient (CBD) administered orally in multiple therapeutic settings has 
described no consistent findings for systemic AEs.  Based on findings in previous studies of CBD, 
mild skin irritation may occur (see IB for details). 
7.3. Time Period and Frequency for Event Assessment and Follow-up 
All AEs occurring after signing of the consent form through completion of Day 85 Visit will be 
recorded.  AEs arising after the time of initiation of first treatment with study drug will be 
considered treatment emergent AEs (TEAEs).  At each contact with the subject, the investigator 


 
 
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or designee must seek information on AEs by non-leading specific questioning and, as appropriate, 
by examination.  All observed or volunteered AEs, regardless of suspected causal relationship to 
study drug, must be recorded on the AE page of the eCRF. 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits 
and interviews of a study subject presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be recorded. 
Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study drug (assessed only by those with the training and authority to make 
a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study 
must be documented appropriately regardless of relationship. All AEs will be followed to adequate 
resolution.  
Any medical condition that is present at the time that the subject is screened will be recorded in 
the Medical History eCRF and will be considered as Baseline and not reported as an AE. However, 
if the study subject’s condition deteriorates at any time during the study, it will be recorded as an 
AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
7.4. Reporting Procedures 
7.4.1. Adverse Events Reporting 
All AEs will be recorded on the AE eCRF.  For each AE, the name of the event, date of onset, 
relationship to study drug, severity, seriousness (Y/N), whether a medication was used to treat the 
event, date of resolution (or ongoing), and outcome (fatal, recovered/resolved, recovered/resolved 
with sequelae, ongoing) will be noted. 
7.4.2. Serious Adverse Event Reporting 
Each AE will be independently judged by the investigator in terms of seriousness.  A SAE is 
defined in Section 7.1.2.  
All SAEs will be reported to the sponsor via e-mail or phone call within 24 hours of becoming 
aware of the event, whether or not the serious events are deemed drug-related.  All serious event 
reporting will adhere to 21 CFR 312.32 for Investigational New Drugs (IND) and to the Guidance 
for 
Industry 
and 
Investigators: 
Safety 
Reporting 
Requirements 
for 
INDs 
and 
Bioavailability/Bioequivalence, dated December 2012. The HREC/IRB will be notified of the 
Alert Reports. 
All AEs will be followed until resolution or until the investigator determines that the subject’s 
status has returned to normal or has stabilized. 


 
 
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7.4.3. Reporting of Pregnancy 
As part of the eligibility criteria, WOCBP must agree to use appropriate contraception methods to   
avoid pregnancy during the study.  If a subject does become pregnant, or is suspected of being 
pregnant, the subject will be immediately withdrawn from any further treatment with the study 
drug.  The pregnancy, or suspected pregnancy will be immediately reported to the Medical 
Monitor. 
Any subject that becomes pregnant during the study will be followed to term to collect pregnancy 
outcomes pending acquisition of the subject’s permission. Pregnancy will be followed until the 
outcome of the pregnancy is known (i.e. miscarriage, abortion or birth), and the newborn condition 
is reported.  No further follow up is required after birth unless specifically requested by the medical 
monitor. It will be the responsibility of the study’s Medical Monitor to follow the subject after the 
subject’s withdrawal from the study.   
7.5. Safety Oversight 
Oversight of the safety of the study will be the responsibility of the Medical Monitor.  No Data 
Safety Monitoring Board (DSMB) will be convened for this study.  Safety data will be regularly 
reviewed (monthly at a minimum).  If unexpected safety signals are observed, the Medical 
Monitor, the sponsor, and the HREC/IRB, if necessary, will determine if the study requires a pause 
to further assess the safety signal or termination.     


 
 
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8. CLINICAL MONITORING 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the study is in compliance with the currently approved protocol/amendment(s), with GCP, and 
with applicable regulatory requirement(s).  
Monitoring for this study will be performed by Premier Research.  
On-site monitoring will occur for initial site assessment and training throughout the study and at a 
frequency adequate to assess the above based on the number of subjects enrolled at each site and 
the time from enrollment of the subjects.  Comprehensive source data verification (100%) will be 
conducted.  The monitor should have access to laboratory test reports and other subject records 
needed to verify the entries on the Case Report Form.  The investigator (or his/her designee) agrees 
to cooperate with the monitor to ensure that any problems detected during these monitoring visits 
are resolved. 
A site visit monitoring report will be prepared for each visit.  The sponsor will be provided copies 
of the draft monitoring reports within 10 days of visit.  
Details of clinical site monitoring are documented in the Clinical Monitoring Plan (CMP). The 
CMP describes in detail who will conduct the monitoring, at what frequency monitoring will be 
done, at what level of detail monitoring will be performed, and the distribution of monitoring 
reports.  
Independent audits may be conducted by Premier Research auditors, the sponsor, or regulatory 
agencies to ensure monitoring practices are performed consistently across all participating sites 
and that monitors are following the CMP.  
 


 
 
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9. STATISTICAL CONSIDERATIONS 
9.1. Statistical and Analytical Plans 
A separate Statistical Analysis Plan (SAP) will be prepared for this study.  The statistical 
approaches to analysis of the data are summarized in this protocol.  Further detail on the structure 
of tables, listings, and figures is provided in the SAP.   
9.2. Statistical Hypotheses 
The purpose of this Phase 2a study is to describe the safety and efficacy of treatment with the BTX 
1204 4% Liquid Formulation vs Vehicle with BID dosing in subjects with moderate atopic 
dermatitis.  Exploratory analysis of the study drug’s effect on AD will be evaluated.  None of these 
assessments will use hypothesis testing to assess their treatment effect.   
Should any post-hoc statistical analyses be conducted to present study outcomes, the methods for 
analysis will be described in the final clinical study report.   
9.3. Description of Statistical Methods 
9.3.1. General Approach 
This study will be evaluated using 3 analysis sets: intent-to-treat (ITT), per protocol (PP), and 
safety.  Efficacy conclusions will be drawn from the ITT analysis set.  The ITT analysis set will 
consist of all randomized subjects with at least one post-baseline efficacy assessment and will be 
based on randomized study group, regardless of study drug received.  The PP analysis set will be 
used to support the efficacy findings in the ITT analyses and will include subjects with no major 
protocol deviations.  Safety conclusions will be drawn from the safety analysis set.  The safety 
analysis set will include all subjects that received at least one application of study drug and had at 
least one post-baseline safety assessment with treatment based on study drug received regardless 
of randomization group.   
Demographics will be summarized using the safety analysis set by baseline age, gender, race, 
ethnicity, height, and weight.  The primary efficacy analysis will be conducted on the ITT 
population.  For continuous variables, the mean, standard deviation (SD), median, and range will 
be presented along with the 95% confidence interval (CI).   Categorical variables will be 
summarized by proportions along with the 95% CI. 
9.3.2. Safety Analyses 
Safety analyses will include summaries of AEs, TEAEs, serious AEs (SAEs), and changes in 
laboratory assessments.  AEs, TEAEs and SAEs will be coded using the MedDRA dictionary and 
summarized by treatment group, the number of subjects reporting events, system organ class, 
preferred term, severity, relationship to study drug, and seriousness. A list of subjects who 


 
 
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prematurely discontinue from the study due to an AE and the reason for discontinuation will be 
provided. 
The number and percentage of subjects reporting each medication will be summarized.  
Medications taken by each subject will be listed. 
Changes in laboratory parameters from Baseline to Day 85 will be summarized using shift tables 
to evaluate for trends.  Abnormal laboratory findings will be summarized and listed by subject. 
Concomitant medications will be mapped to ATC Level 2 using the WHODrug dictionary.  The 
number and percentage of subjects reporting each medication will be summarized.  Medications 
taken by each subject will be listed. 
9.3.3. Efficacy Analyses 
The efficacy variables include the IGA, BSA of AD, Signs of AD score, EASI score, and pruritus 
scores (I-NRS) collected at Screening/Baseline and all subsequent study visits and the WI-NRS 
recorded daily by subjects.  
The primary efficacy endpoint for the study is the proportion of subjects with IGA success defined 
as an IGA score of Clear (0) or Almost Clear (1) with at least a 2-grade improvement from Baseline 
at Day 85.  The IGA will be dichotomized into “success” and “failure” at study Day 15, Day 29, 
Day 57, and Day 85.  Success on IGA defined as a score of Clear (0) or Almost Clear (1) and at 
least a 2-grade improvement from Baseline at Day 15, Day 29, Day 57, and Day 85 will be 
analyzed using logistic regression, adjusting for Baseline IGA.   
Summary statistics will be prepared for the change from Baseline in the percent of BSA affected 
by AD at Days 15, 29, 57, and 85.  The change from Baseline in BSA of AD will be analyzed used 
ANCOVA with Baseline BSA of AD and treatment as covariates.  
Summary statistics will be presented for the change from baseline in each of the Signs of AD 
scores (erythema, exudation, excoriation, induration/papulation, and lichenification) at each 
timepoint (Day 15, Day 29, Day 57 and Day 85).  A total score will be calculated based on the 
sum of each of the Signs of AD (0, 1, 2, or 3; max score of 15) and the change from baseline will 
be summarised for each timepoint.  The change from baseline in Signs of AD score at Day 15, Day 
29, Day 57, and Day 85 will be analyzed used ANCOVA with Baseline Signs of AD score and 
treatment as covariates.   
The proportion of subjects with an EASI 50 and EASI 75 score will be summarized at Day 15, 
Day 29, Day 57, and Day 85 and compared using logistic regression, adjusting for Baseline EASI 
score.  Summary statistics will be prepared for the change from Baseline in the EASI score and 
I-NRS at each timepoint (Day 15, Day 29, Day 57 and Day 85).  
Summary statistics will be prepared for the change from Baseline in the Signs of AD score for the 
target lesion (selected sites) at each timepoint (Day 15, Day 29, Day 57 and Day 85). 


 
 
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Summaries of the pruritus scores (WI-NRS) reported by the subjects in the daily Patient Diary will 
be presented using daily means by treatment and with graphic presentations.  
The percent change from Baseline the EASI will be presented along with the subject’s report of 
pruritus obtained from the Patient Diary.  Time to improvement of pruritus and subject’s 
assessment of the change in their AD from Baseline to Day 85 will be presented. 
9.3.4. Adherence and Retention Analyses 
Compliance with study drug administration will be summarized based on dosing information from 
the clinical sites and based on the diary information obtained from subjects.  Subjects who drop-
out from the study for any reason will be summarized.   
9.3.5. Baseline Descriptive Statistics 
Demographics/Baseline characteristics will be summarized by age, gender, race, ethnicity, height, 
weight, and BSA of AD.  The year of AD diagnosis will be captured to calculate and summarize 
the duration of AD. 
9.3.6. Planned Interim Analyses 
No formal interim analysis is planned.  Blinded subject data will be reviewed as it is generated to 
monitor for any safety signals and to ensure that the study is being appropriately executed.  
9.3.7. Multiple Comparison/Multiplicity 
This Phase 2a study is designed to identify the response to BTX 1204 relative to vehicle.  Statistical 
tests applied to the outcomes will be exploratory.  No adjustments for Type 1 error will occur.   
9.3.8. Handling of Missing Data 
The primary method of handling missing efficacy data in the ITT analysis set will be based on 
LOCF.  Other imputation methods (e.g., mixed model for repeated measurement [MMRM]) may 
be used as  sensitivity analyses.  
All safety analyses will be conducted using the safety analysis set. No imputations will be made 
for missing safety data. 
9.3.9. Tabulation of Individual Response Data 
Individual response data will be presented in data listings.     
9.4. Sample Size 
The sample size for this study is based on clinical considerations only.  Subjects will be 
randomized 1:1 with 100 subjects in each treatment group for a total 200 subjects. This is 
considered adequate to evaluate the safety and tolerability and preliminary information on efficacy 


 
 
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of twice daily BTX 1204 4% in the treatment of moderate atopic dermatitis in subjects aged 12 to 
70 years of age.    
9.5. Measures to Minimize Bias 
9.5.1. Enrollment/Randomization/Masking Procedures 
A randomization code will be prepared by an unblinded statistician.  This statistician will be the 
only person aware of the randomization code.  Randomization will be 1:1 (100 active: 100 vehicle) 
and done by site.  Once a subject is deemed eligible to enroll, randomization will occur.  The site 
will contact the IWRS to receive the kit/bottle number(s) to be used for that subject throughout the 
study.   
Study drug, active or vehicle, will be labelled identically except for the kit/bottle numbers.  All 
bottles of study drug will contain 100 mL of either BTX 1204 4% (w/w) Liquid Formulation or 
Vehicle.  The vehicle study drug is indistinguishable from the active study drug.     
9.5.2. Breaking the Study Blind/Subject Code 
During the study, the randomization code will not be broken except in the case of a safety concern, 
either for an individual subject or for the entire study. 
If a subject has an adverse event that may necessitate unblinding of the randomization code, the 
site will contact the CRO and sponsor to discuss if there are options other than unblinding.  If the 
site and sponsor agree that unblinding is in the best interests of the subject, the unblinded 
statistician will be contacted to conduct the unblinding.  Sealed, unblinding envelopes will be 
maintained at the investigators’ site only for circumstances where the CRO or sponsor cannot be 
contacted and the subject is in imminent danger without knowledge of their treatment.   
At the completion of the study, the blind will be broken only after all data on all subjects have 
been entered into the database and the database is locked.  Database lock procedures will follow 
Premier Research SOPs. 
 


 
 
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10. QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site and laboratory participating in this study will have SOPs for quality management 
that describe: 
• How data will be evaluated for compliance with the protocol, ethical standards, regulatory 
compliance, and accuracy in relation to source documents.  
• The documents to be reviewed (e.g., eCRFs, clinic notes, product accountability records, 
specimen tracking logs, questionnaires, audio or video recordings), who is responsible, and 
the frequency for reviews.  
• Who will be responsible for addressing QA issues (e.g., correcting procedures that are not 
in compliance with protocol) and QC issues (e.g., correcting errors in data entry).  
• Staff training methods and how such training will be tracked.  
• If applicable, calibration exercises conducted prior to and during the study to train 
examiners and maintain acceptable intra-and inter-examiner agreement.  
QC procedures will be implemented beginning with the data entry system and data QC checks that 
will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution.  
Following written SOPs, the clinical study monitors will verify that the clinical trial is conducted 
and data are generated, documented (recorded), and reported in compliance with the protocol, 
GCP, and the applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)).  
The investigational site will provide direct access to all trial related sites, source data/documents, 
and reports for monitoring and auditing by the sponsor, and inspection by local and regulatory 
authorities. 
 


 
 
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11. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
This research will be carried out in accordance with the protocol, the ICH harmonized tripartite 
guideline regarding GCP (E6 Consolidated Guidance, June 1996), the National Statement on 
Ethical Conduct in Human Research (updated May 2015), and the ethical principles set forth in 
the Declaration of Helsinki. 
11.1. 
Regulatory, Ethical, and Study Oversight Considerations 
11.1.1. Informed Consent/Assent Process 
It is the responsibility of the investigator, or a person designated by the investigator (if acceptable 
by local regulations), to obtain written informed consent/assent from each subject participating in 
this study after adequate explanation of the aims, methods, objectives and potential hazards of the 
study.  It must also be explained to the subjects that they are completely free to refuse to enter the 
study or to withdraw from it at any time for any reason.  In states or institutions where permission 
is required from a legal guardian and the child is required to assent to participate, the appropriate 
assent-permission process will be followed according to the relevant local and/or state laws.  
Appropriate IRB/EC-approved forms for obtaining written informed consent/assent will be 
provided by the investigator or by the sponsor or its designee.   
The case report forms for this study contain a section for documenting informed consent/assent 
and this must be completed appropriately.  If new safety information results in significant changes 
in the risk/benefit assessment, the consent/assent form will be reviewed and updated if necessary.  
All subjects (including those already being treated) will be informed of the new information, given 
a copy of the revised form and be re-consented/assented to continue in the study. 
11.1.2. Institutional Review Board (IRB)/Ethics Committee (EC) 
This protocol, the informed consent/assent form and any accompanying material provided to the 
subject (such as subject information sheets or descriptions of the study used to obtain informed 
consent/assent) as well as any advertising or compensation given to the subject, will be reviewed 
by the IRB/EC, and the study will not start until the IRB/EC has approved the protocol or a 
modification thereof.  The IRB/EC is constituted and operates in accordance with the principles 
and requirements described in 21 CFR 56, ICH E6, and the National Statement on Ethical Conduct 
in Human Research (updated May 2015).  
Protocol modifications to this study must be made only after consultation between an appropriate 
representative of the sponsor and the investigator.  Protocol amendments must be prepared and 
approved by the sponsor and reviewed and approved by the IRB/EC prior to implementation. 
11.1.3. Subject and Data Confidentiality 
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples 


 
 
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in addition to the clinical information relating to subjects. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or data will be released to any unauthorized third party without 
prior written approval of the sponsor.  
The study monitor, other authorized representatives of the sponsor, or representatives of the 
IRB/EC may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for 
the subjects in this study. The clinical study site will permit access to such records.  
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location 
as described in Section 12.1.1.  
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored at the CRO. This will not include the subject’s contact or 
identifying information. Rather, individual subjects and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by 
clinical sites and by the clinical sites’ research staff will be secured and password protected. At 
the end of the study, all study databases will be de-identified and archived at the CRO and 
ultimately with the sponsor. 
11.1.4. Research Use of Stored Human Samples, Specimens or Data 
Samples and data collected under this protocol will be used to study the safety of the study drug, 
BTX 1503 liquid formulation. No genetic testing will be performed.  Samples and data will be 
stored using codes assigned by the clinical study site, the CROs, and/or the laboratories assessing 
the samples. Data will be kept in password-protected computers. Only those entities participating 
in the study will have access to the samples and data.  
The study involves taking digital photographs of a target lesion at selected sites. The subject or 
subject’s parent/guardian will consent/assent, in advance of any photographs being taken, to the 
taking, copyright, publication, and use of their photographs.  The subject’s face will not be 
included in the photos. The photographs will be part of the study record and will be sent to the 
sponsor and regulatory agencies. The photographs will only be linked to the subject’s study code 
and not the subject’s name.   
11.1.5. Future Use of Stored Specimens 
All blood and urine samples used for assessment or study drug safety will be destroyed after 
analysis.  No specimens will be stored for future use. 
11.1.6. Key Roles and Study Administration 
The sponsor of this study is Botanix Pharmaceuticals Ltd (Botanix).  Botanix has engaged Premier 
Research (Durham, North Carolina, US) to oversee the conduct of the study.  Premier will conduct 


 
 
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the data management, clinical monitoring and statistical management of the study.  The medical 
monitor for this study will be provided by Premier.  His/her responsibility will be to oversee the 
safety of subjects in the study.   
The IRB/EC, which protects the rights and welfare of subjects, will be either local or centralized 
based on the study site.  Central IRBs will be preferentially used when possible.  Clinical sites 
outside of the US, will have IRB/EC oversight based on local and national requirements. 
Photography of a target lesion at selected sites will be performed utilizing equipment from a 
photography vendor.  The vendor will provide a Photography Manual describing correct 
techniques for photographing subjects.  Photographs from the study are the property of Botanix 
and will become part of the study record.   
Study drug will be manufactured and distributed in Australia by PCI Pharma Services for 
Australian sites.  In the United States, The Coghlan Group (TCG; Bastrop, Texas, USA) is 
responsible for packaging, labeling, and distribution of the study drug for US sites.  
A qualified vendor will act as the central lab for analysis of the blood and urine samples.  Results 
will be provided to the sites for their subject management and to Premier for data analysis.   
There will be no DSMB for this study.  Blinded safety data will be reviewed in real-time by the 
medical monitor to assure subject safety. 


 
 
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12. DATA HANDLING AND RECORD KEEPING 
12.1.1. Data Handling and Record Keeping 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
confidentiality of subjects.  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site principal investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported.  
For each subject enrolled, an eCRF must be completed by an authorized delegate from the study 
staff and signed by the principal investigator.  If a subject withdraws from the study, the reason 
must be noted on the eCRF.  If a subject is withdrawn from the study because of a treatment-
limiting adverse event, thorough efforts should be made to clearly document the outcome.  The 
investigator should ensure the accuracy, completeness, and timeliness of the data reported to the 
sponsor in the eCRF’s and in all required reports. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into the electronic data capture (EDC) system, a 21 CFR 
Part 11-compliant data capture system provided by the CRO. The data system includes password 
protection and internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
The investigator should understand that source documents for this trial should be made available 
to appropriately qualified personnel from the sponsor or its designees or to health authority 
inspectors after appropriate notification.  The verification of the eCRF Data must be by direct 
inspection of source documents. 
Source documents will be maintained for recording data for each subject enrolled in the study. 
Data reported in the eCRF derived from source documents should be consistent with the source 
documents or the discrepancies should be explained and captured in a progress note and 
maintained in the subject’s official study record.  
The investigator shall supply the sponsor or its designee on request with any required background 
data from the study documentation or clinic records.  This is particularly important when data on 
the electronic Case Report Forms requires clarification.  In case of special problems/and or 
governmental queries or requests for audit inspections, it is also necessary to have access to the 
complete study records, provided that subject confidentiality is protected.  
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Examples 
of these original documents and data records include, but are not limited to, hospital records, clinic 
and office charts, laboratory notes, memoranda, subjects’ memory aids or evaluation checklists, 


 
 
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subject diaries, pharmacy dispensing records, recorded audio tapes of counseling sessions, 
recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, 
x-rays, and subject files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical trial.  
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. Black ink is required to ensure clarity of reproduced copies. When making 
changes or corrections, cross out the original entry with a single line, and initial and date the 
change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE 
ORIGINAL.  
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified.  These documents should 
be classified into two different separate categories (1) Investigator’s Study File, and (2) Subject 
clinical source documents. The Investigator’s Study File will contain the protocol/amendments, 
Case Report and Query Forms, IRB/EC and governmental approval (as appropriate) with 
correspondence, sample informed consent/assent, study drug records, staff curriculum vitae and 
authorization forms and other appropriate documents/correspondence. All records defined in 21 
CFR 312.57 will be kept on file. 
The investigator must keep these two categories of documents on file for at least 2 years after the 
latest of the following: completion, discontinuation of the study, or the regulatory submission for 
which the study is being performed is no longer under review.  After that, the documents may be 
destroyed, subject to local regulations. 
Should the investigator wish to assign the study records to another party or move them to another 
location, the sponsor must be notified in advance. 
If the investigator cannot guarantee this archiving requirement at the investigational site for any or 
all of the documents, special arrangements must be made between the investigator and the sponsor 
to store these in a sealed container(s) off-site so that they can be returned sealed to the investigator 
in case of a regulatory audit.  Where source documents are required for the continued care of the 
subject, appropriate copies should be made for storing outside of the site. 
12.1.2. Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or other study 
requirements (e.g., SOPs, Laboratory Manuals, etc).  The noncompliance may be either on the part 
of the subject, the investigator, or the study site staff.  As a result of deviations, corrective actions 
are to be developed by the site and implemented promptly.  
These practices are consistent with ICH E6:  
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 5.1 Quality Assurance and Quality Control, section 5.1.1  


 
 
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• 5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
It is the responsibility of the site to use continuous vigilance to identify and report deviations within 
5 working days of identification of the protocol deviation, or within 5 working days of the 
scheduled protocol-required activity. All deviations must be addressed in study source documents 
and reported to the clinical study monitor or to the CRO.  Protocol deviations must be sent to the 
IRB/EC per their guidelines. The site investigator/study staff is responsible for knowing and 
adhering to their IRB/EC requirements.  
It is not anticipated that waivers of eligibility requirements will be granted for any subjects.  
However, if eligibility requirements are waived in special circumstances, waivers must be 
approved by the medical monitor and the sponsor before a subject may be enrolled.  
Documentation of granted waivers will be maintained in the investigator’s and sponsor’s files. 
12.1.3. Publication and Data Sharing Policy 
The results of this study may be published or presented at scientific meetings.  The investigator 
agrees to submit all manuscripts or abstracts to Botanix Pharmaceuticals at least 30 days prior to 
submission.  This allows Botanix Pharmaceuticals to protect proprietary information and to 
provide comments based on information from other studies that may not yet be available to the 
investigator. 
In accordance with standard editorial and ethical practice, Botanix Pharmaceuticals will generally 
support publication of multicenter trials in their entirety.  In this case, a coordinating investigator 
will be designated by mutual agreement.  Authorship will be determined by mutual agreement. 
12.2. 
Conflict of Interest Policy 
The independence of this study from any actual or perceived influence is critical.  Therefore, any 
actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, 
or any aspect of this trial will be disclosed and managed.  Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is 
appropriate to their participation in the study. The study leadership has established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 


 
 
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13. LITERATURE REFERENCES 
Ben-Shabat S, Hanus LO, Katzavian G, Gallily R. New cannabidiol derivatives: synthesis, binding 
to cannabinoid receptor, and evaluation of their antiinflammatory activity. J Med Chem. 2006; 
49:1113-1117. 
Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of 
inflammation on oxidative stress. Free Radic Biol Med. 2011; 51:1054-1061. 
Clinical Trials database (ClinicalTrials.gov) in August 2018 
 De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C et al. Cannabidiol 
reduces intestinal inflammation through the control of neuroimmune axis. PLoS One. 2011; 
6:e28159 [8pp]. 
D'Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic 
dermatitis: design, development, and potential place in therapy. Drug Des Devel Ther. 2017; 
11:1473-1480. 
Esposito G, Scuderi C, Valenza M, Togna GI, Latina V, De Filippis D et al. Cannabidiol reduces 
Aβ-induced neuroinflammation and promotes hippocampal neurogenesis through PPARγ 
involvement. PLoS One. 2011; 6:e28668 [8pp]. 
Faubert Kaplan BL, Rockwell CE, Kaminski NE. Evidence for cannabinoid receptor-dependent 
and -independent mechanisms of action in leukocytes. J Pharmacol Exp Ther. 2003;306:1077-
1085. 
Fernandez-Ruiz J, Sagredo O, Pazos M, et al, Cannabidiol for Neurodegenerative Disorders: 
Important New Clinical Applications for this Phytocannabinoid? Br J Clin Pharmacol 2012: 75(2); 
323-333 
Fouad AA, Jresat I. Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury 
in rats. Eur J Pharmacol. 2011; 670:216-223.  
Fouad AA, Al-Mulhim AS, Jresat I. Cannabidiol treatment ameliorates ischemia/reperfusion renal 
injury in rats. Life Sci. 2012; 91:284-292.  
Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. 
Expert Rev Clin Immunol. 2017; 13:425-437.  
Giacoppo S, Galuppo M, Pollastro F, Grassi G, Bramanti P, Mazzon E. A new formulation of 
cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune 
encephalomyelitis. Daru. 2015; 23:48.  
Guttman-Yassky E, Krueger JG, Lebwohl MG. Systemic immune mechanisms in atopic dermatitis 
and psoriasis with implications for treatment. Exp Dermatol. 2017 [Epub ahead of print – Mar. 7, 
2017]. 


 
 
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Hanifin M and Rajka G. Diagnostic features of atopic dermatitis, Acta Derm Venereol (Stockh) 
1980. 92 (Suppl): 44-7 
Harvey BS, Sia TC, Wattchow DA, Smid SD. Interleukin 17A evoked mucosal damage is 
attenuated by cannabidiol and anandamide in a human colonic explant model. Cytokine. 2014; 
65:236-244. 
Hegde VL, Nagarkatti PS, Nagarkatti M. Role of myeloid-derived suppressor cells in amelioration 
of experimental autoimmune hepatitis following activation of TRPV1 receptors by cannabidiol. 
PLoS One. 2011; 6:e18281 [12pp].  
Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH. Cannabidiol-induced 
lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol. 2009;60(suppl 3):99-103. 
Kozela E, Juknat A, Kaushansky N, Rimmerman N, Ben-Nun A, Vogel Z. Cannabinoids decrease 
the th17 inflammatory autoimmune phenotype. J Neuroimmune Pharmacol. 2013; 8:1265-1276.  
Kozela E, Juknat A, Kaushansky N, Ben-Nun A, Coppola G, Vogel Z. Cannabidiol, a non-
psychoactive cannabinoid, leads to EGR2-dependent anergy in activated encephalitogenic T cells. 
J Neuroinflammation. 2015; 12:52 [16pp].  
Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene networks 
mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T 
cells. J Neuroinflammation. 2016; 13:136 [19pp].  
Lee W-S, Erdelyi K, Matyas C, Mukhopadhyay P, Varga ZV, Liaudet L et al. Cannabidiol limits 
T cell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and 
organ transplantation. Mol Med. 2016; 22:136-146.  
Libro R, Scionti D, Diomede F, Marchisio M, Grassi G, Pollastro F et al. Cannabidiol modulates 
the immunophenotype and inhibits the activation of the inflammasome in human gingival 
mesenchymal stem cells. Front Physiol. 2016; 7:559 [17pp].  
Mukhopadhyay P, Rajesh M, Horváth B, Bátkai S, Park O, Tanchian G et al. Cannabidiol protects 
against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, 
oxidative/nitrative stress, and cell death. Free Radic Biol Med. 2011; 50:1368-1381.  
National Eczema Organization. Understanding Your Atopic Dermatitis. San Rafael (CA): National 
Eczema 
Organization; 
2017. 
Available 
at: 
https://nationaleczema.org/eczema/types-of-
eczema/atopic-dermatitis/ [Last accessed: June 16, 2017]. 
Nowicki R, Trzeciak M, Wilkowska A, Sokolowska-Wojdylo M, Lugowska-Umer H, Baranska-
Rybak W et al. Atopic dermatitis: current treatment guidelines. Statement of the experts of the 
Dermatological Section, Polish Society of Allergology, and the Allergology Section, Polish 
Society of Dermatology. Postepy Dermatol Alergol. 2015; 32:239-249.  
Olah A, Toth B, Borbiro I, et al, Cannabidiol exerts sebostatic and anti-inflammatory effects on 
human sebocytes, J Clin Invest 2014; 124(9); 3713-3724 


 
 
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Petrosino S, Verde R, Vaia M, Allarà M, Iuvone T, Di Marzo V (2018): Anti-inflammatory 
Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact 
Dermatitis. J Pharmacol Exp Ther. 365(3): 652-663.  
Ribeiro A, Ferraz-De-Paula V, Pinheiro ML, Vitoretti LB, Mariano-Souza DP, Quinteiro-Filho 
WM et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in 
a murine model of acute lung injury: role for the adenosine A(2A) receptor. Eur J Pharmacol. 2012; 
678:78-85.  
Tan Q, Yang H, Liu EM, Wang H. Establishing a role for interleukin-17 in atopic dermatitis-
related skin inflammation. J Cutan Med Surg. 2017; 21:308-315.  
Tawada C, Kanoh H, Nakamura M, Mizutani Y, Fujisawa T, Banno Y et al. Interferon- γ decreases 
ceramides with long-chain fatty acids: possible involvement in atopic dermatitis and psoriasis. J 
Invest Dermatol. 2014; 134:712-718.  
Volkow N, The Biology and Potential Therapeutic Effects of Cannabidiol: "Cannabidiol: Barriers 
to Research and Potential Medical Benefits" Presentation to NIDA June 24, 2015 
Weiss L, Zeira M, Reich S, Slavin S, Raz I, Mechoulam R et al. Cannabidiol arrests onset of 
autoimmune diabetes in NOD mice. Neuropharmacology. 2008; 54:244-249.  
Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a 
non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J 
Dermatol Sci. 2007; 45:87-92.  
Yeshurun M, Shpilberg O, Herscovici C, Shargian L, Dreyer J, Peck A, et al. Cannabidiol for the 
prevention of graft-versus-hostdisease after allogeneic stem cell transplantation: results of a phase 
II study. Biol Blood Marrow Transplant 2015a; 21:1770-1775.  
Yeshurun M, Shpilberg O, Herscovici K, Shargian L, Dreyer J, Peck A et al. Cannabidiol for the 
prevention of graft-versus-host-disease after allogeneic stem cell transplantation: results of a phase 
I/II study. Biol Blood Marrow Transplant. 2015b; 21:S353-S354 [abstract 514].  
 
 
 
 
 


 
 
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APPENDIX A – CRITERIA OF HANNIFIN AND RAJKA  
Hanifin and Rajka Diagnostic Criteria for Atopic Dermatitis (AD) 
Major criteria: Must have three or more of: 
1. Pruritus 
2. Typical morphology and distribution 
• 
Flexural lichenification or linearity in adults 
• 
Facial and extensor involvement in infants and children 
3. Chronic or chronically-relapsing dermatitis 
4. Personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis) 
Minor criteria: Should have three or more of: 
1. Xerosis 
2. Ichthyosis, palmar hyperlinearity, or keratosis pilaris 
3. Immediate (type 1) skin-test reactivity 
4. Raised serum IgE 
5. Early age of onset 
6. Tendency toward cutaneous infections (especially S aureus and herpes simplex) or 
impaired cell-mediated immunity 
7. Tendency toward non-specific hand or foot dermatitis 
8. Nipple eczema 
9. Cheilitis 
10. Recurrent conjunctivitis 
11. Dennie-Morgan infraorbital fold 
12. Keratoconus 
13. Anterior subcapsular cataracts 
14. Orbital darkening 
15. Facial pallor or facial erythema 
16. Pityriasis alba 
17. Anterior neck folds 
18. Itch when sweating 
19. Intolerance to wool and lipid solvents 
20. Perifollicular accentuation 
21. Food intolerance 
22. Course influenced by environmental or emotional factors 
23. White dermographism or delayed blanch 
 

SAP_001.pdf: 
 
 
 
 
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STATISTICAL ANALYSIS PLAN 
Protocol Number: 
BTX.2018.003 
 
 
Study Title: 
A Randomized, Double-Blind, Vehicle-
Controlled Study of the Safety, 
Tolerability and Efficacy of BTX 1204 in 
Patients with Moderate Atopic Dermatitis 
 
 
Development Phase of Study: 
2a 
 
 
Sponsor: 
Botanix Pharmaceuticals Ltd 
Sponsor Contact: 
Stephane Levy 
 
 
Statistical Analysis Plan based on Protocol Version: 
1.2 (04FEB2019) 
 
 
Statistical Analysis Plan Date: 
13 DEC 2019 
Statistical Analysis Plan Version: 
v1 
 
 
NCT03824405




 
 
 
 
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SAP Change History 
Version Date 
Summary of Changes  
Author 
1 13DEC2019 Original document 
Laura Cole 
 
 


 
 
 
 
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TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................7 
2. 
INTRODUCTION .................................................................................................................8 
3. 
STUDY OBJECTIVES .........................................................................................................9 
4. 
STUDY DESIGN ...................................................................................................................9 
4.1 Overall Study Design ......................................................................................................9 
4.1.1 
Schedule of Visits and Assessments .................................................................9 
4.1.2 
Method of Assigning Subjects to Treatment Groups ......................................10 
4.1.3 
Blinding ...........................................................................................................10 
5. 
EFFICACY AND SAFETY ENDPOINTS .......................................................................10 
5.1 Efficacy Endpoints ........................................................................................................10 
5.1.1 
Primary Efficacy Endpoints ............................................................................10 
5.1.2 
Secondary Efficacy Endpoints ........................................................................11 
5.1.3 
Exploratory Efficacy Endpoints ......................................................................11 
5.2 Safety Endpoints ...........................................................................................................11 
6. 
STATISTICAL AND ANALYTICAL PLANS ................................................................12 
6.1 General Methodology ...................................................................................................12 
6.1.1 
Statistical Analysis ..........................................................................................12 
6.1.2 
Baseline Definition ..........................................................................................12 
6.1.3 
Visit Windowing .............................................................................................13 
6.1.4 
Adjustments for Covariates .............................................................................14 
6.1.5 
Handling of Dropouts or Missing Data ...........................................................14 
6.1.6 
Interim Analyses and Data Monitoring ...........................................................14 
6.1.7 
Multicenter Studies ..........................................................................................14 
6.1.8 
Multiple Comparisons/Multiplicity .................................................................15 
6.1.9 
Use of an Efficacy Subset of Subjects .............................................................15 
6.1.10 Active-Control Studies Intended to Show Equivalence ..................................15 
6.1.11 Examination of Subgroups ..............................................................................15 
6.2 Disposition of Subjects .................................................................................................15 
6.3 Protocol Deviations .......................................................................................................16 
6.4 Data Sets Analyzed .......................................................................................................16 
6.4.1 
Randomized Population ..................................................................................16 


 
 
 
 
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6.4.2 
Intent-to-Treat Population ...............................................................................16 
6.4.3 
Modified Intent-to-Treat Population ...............................................................16 
6.4.4 
Safety Population ............................................................................................16 
6.4.5 
Per-Protocol Population ..................................................................................17 
6.5 Demographic and Other Baseline Characteristics ........................................................17 
6.6 Prior and Concomitant Medications .............................................................................18 
6.7 Concomitant Antibiotic Therapies ................................................................................18 
6.8 Analysis of Efficacy ......................................................................................................18 
6.8.1 
Primary Efficacy Analysis ...............................................................................18 
6.8.2 
Secondary Efficacy Analysis ...........................................................................19 
6.8.2.1 
Signs of Atopic Dermatitis at Day 85 ............................................19 
6.8.2.2 
Proportion of Subjects with an IGA of Clear (0) or Almost 
Clear (1) at Day 85 .......................................................................19 
6.8.2.3 
Proportion of Subjects with at least a 2-Grade Improvement 
in IGA at Day 85 ..........................................................................19 
6.8.2.4 
Percent of Total Body Surface Area Affected by Atopic 
Dermatitis at Day 85 .....................................................................19 
6.8.2.5 
Time to Achieve IGA Success .......................................................19 
6.8.2.6 
I-NRS at Day 85.............................................................................19 
6.9 Exploratory Efficacy Analysis ......................................................................................20 
6.9.1.1 
Signs of Atopic Dermatitis at Days 15, 29 and 57 .........................20 
6.9.1.2 
Percent of Total Body Surface Area Affected by Atopic 
Dermatitis at Days 15, 29 and 57 .................................................20 
6.9.1.3 
Investigator Global Assessment at Days 15, 29 and 57 .................20 
6.9.1.4 
Signs of Atopic Dermatitis at Target Lesions (at selected 
photography sites only) at Days 29, 57 and 85 ............................21 
6.10 Sensitivity Analyses ......................................................................................................21 
6.10.1 Repeated Measures ..........................................................................................21 
6.10.2 Tipping Point ...................................................................................................21 
6.11 Safety Evaluation ..........................................................................................................22 
6.11.1 Extent of Exposure ..........................................................................................22 
6.11.2 Adverse Events ................................................................................................22 
6.11.3 Drug Abuse and Liability Assessments ...........................................................23 
6.11.4 Clinical Laboratory Evaluation .......................................................................23 
6.11.5 Other Observations Related to Safety .............................................................24 
6.11.5.1 
Physical Examination.....................................................................24 


 
 
 
 
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7. 
DETERMINATION OF SAMPLE SIZE .........................................................................24 
8. 
CHANGES IN THE PLANNED ANALYSES..................................................................24 
9. 
REFERENCES ....................................................................................................................25 
10. INDEX OF PLANNED TABLES ......................................................................................27 
11. INDEX OF PLANNED FIGURES ..................................................................................102 
12. INDEX OF PLANNED LISTINGS .................................................................................106 
 
 


 
 
 
 
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1. LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AD 
atopic dermatitis 
AE(s) 
adverse event(s) 
ANCOVA 
analysis of covariance 
ATC 
anatomical therapeutic chemical 
AUS 
Australia  
BID 
twice daily 
BSA 
Body Surface Area 
CBC 
Complete Blood Count 
CBD 
Cannabidiol 
eCRF(s) 
Electronic case report form(s) 
CRO 
Clinical research organization 
g 
grams 
g/day 
grams/day 
IGA 
Investigator’s Global Assessment 
IL 
Interleukin 
I-NRS 
Itching-Numerical Rating Score 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web-based Randomization System 
kg 
kilograms 
LOCF 
last observation carried forward 
LSMean  
least squares mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified Intent-to-Treat 
n 
number of observations 
N 
number of subjects (sample size) 
NZ 
New Zealand 
PP 
per-protocol 
PT(s) 
preferred term(s) 
QST 
QST Consultations, Ltd. 
SAE(s) 
serious adverse event(s) 
SAS® 
Statistical Analysis System (SAS® Institute Inc., Cary, NC) 


 
 
 
 
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SD 
standard deviation 
SOC 
system organ class 
TEAE(s) 
treatment-emergent adverse event(s) 
US 
United States 
WHO-DDE 
World Health Organization Drug Dictionary 
2. INTRODUCTION 
Atopic dermatitis (AD) is an inflammatory cutaneous disease which may co-exist with other 
immunoglobulin E (IgE)-dependent atopic diseases such as allergic rhinitis, bronchial asthma, 
and food allergy. [14] The disease is a skin disorder which presents itself as itchy, inflamed, red, 
and possibly lichenified (i.e. thickened) skin with affected areas potentially distributed widely 
over the body. [13] The pathogenesis of the disease is thought to involve an acute T-helper 2 
(Th2) cell response followed by a chronic response involving additional T-helper populations; 
although more recent research suggests that Th2 cells and a more generalized T-cell response are 
present during both acute and chronic phases. [6] The importance of Th2 cells and interleukin 
(IL)-4 and IL-13 signaling in the disease is supported by the effectiveness of dupilumab, a 
human monoclonal antibody specific to IL-4Rα that can block IL-4 and IL-13 signaling, to 
improve many symptoms of AD including pruritus, and reduction in AD area and severity. [6] 
Literature indicates that Cannabidiol (CBD) can inhibit the migration, proliferation and cell 
maturation processes involved in Th17, Th1, and Th2 immune responses. [9, 10, 11] These are 
considered critical immune pathways involved in the pathophysiology of AD. [8] CBD may have 
beneficial effects on AD due to direct antioxidant effects, and ability to improve antioxidant 
status in models of inflammation and autoimmune disease. [1, 2, 3, 4, 12, 5, 7, 11] Finally, CBD 
may also provide a therapeutic benefit for the treatment of AD by modulating the inflammatory 
response regulated by keratinocytes. CBD inhibited the production of monocyte chemotactic 
protein-2 (MCP-2), IL-6, IL-8, and tumor necrosis factor-α in polyinosinic-polycytidylic acid 
stimulated human keratinocyte (HaCaT) cells. [16] CBD has also been shown to directly inhibit 
the proliferation of keratinocytes. [17] 
This study is the second study in evaluating the use of BTX 1204 4% (w/w) in subjects with AD.  
Botanix Pharmaceuticals' BTX 1204 contains the active pharmaceutical ingredient, cannabidiol 
(CBD; 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol). CBD 
is a member of a broader family of compounds known as cannabinoids, a class of compounds 
originally derived from the cannabis sativa plant. [15] 


 
 
 
 
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The preliminary efficacy of BTX 1204 4% (w/w) was evaluated in a Phase 1b, randomized, 
double-blind, vehicle-controlled study. After only 4 weeks of treatment, subjects receiving BTX 
1204 4% (w/w) had improvements in the Signs of AD score compared to treatment with Vehicle. 
A total of 34.8% of subjects receiving BTX 1204 had a ≥ 4-point improvement in the Signs of 
AD score compared to 18.2% of subjects receiving vehicle. Improvement was observed 
primarily in erythema, exudation and lichenification.  
This study is intended to establish safety, tolerability and efficacy in subjects with moderate AD 
treated twice daily (BID) with BTX 1204 4% (w/w) Liquid Formulation compared to subjects 
treated with Vehicle for 12 weeks. 
3. STUDY OBJECTIVES 
The objective of this study is to determine the safety, tolerability and efficacy of BTX 1204 4% 
(w/w) in subjects with moderate atopic dermatitis. 
4. STUDY DESIGN 
4.1 
Overall Study Design 
This is a randomized, double-blind, vehicle-controlled, Phase 2a study in subjects with moderate 
AD. Approximately two hundred (200) subjects randomized 1:1 (100 active: 100 vehicle) will be 
enrolled.  
There will be two dose groups. All subjects will apply study drug for 84 days. 
• 
BTX 1204 4% BID, or 
• 
Vehicle BID 
At the Baseline visit, qualified subjects will be randomized to treatment using an Interactive 
Web-based Randomization System (IWRS). The study will be a total of up to 112 days in 
duration; screening period (up to 28 Days), and 84 days of treatment. During the study, subjects 
will return to the study clinic at Days 15, 29, 57, and 84 (Study Exit). 
4.1.1 
Schedule of Visits and Assessments 
The schedule of assessments can be found in Section 6.3.9 of the protocol. 


 
 
 
 
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4.1.2 
Method of Assigning Subjects to Treatment Groups 
A randomization scheduled will be generated by a statistician(s) from QST Consultations, Ltd. 
(QST) Statistical Services department who is not associated with the day-to-day conduct of the 
study, using a validated system. The randomization list will not be stratified, but stratification by 
site will be accomplished within the IWRS. 
Once a subject is deemed eligible to enroll, randomization will occur using an IWRS. The IWRS 
will assign a study drug kit number based on a predetermined randomization schedule. The kit 
number will be recorded in the electronic case report form (eCRF). Randomization will be 1:1 
(100 active: 100 vehicle). 
4.1.3 
Blinding 
Botanix, the clinical research organization (CRO), the investigator, study site personnel and 
subjects will be blinded to the treatment assignment. The randomization schedule will be kept 
strictly confidential and accessible only to authorized persons. Only when the study has been 
completed, the protocol violations determined, evaluability confirmed, and the study database 
locked will the randomization schedule be released for analysis.  
During the study, the randomization code will not be broken except in the case of a safety 
concern, either for an individual subject or for the entire study. If a subject has an adverse event 
(AE) that may necessitate unblinding of the randomization code, the site will contact the CRO 
and Botanix to discuss if there are options other than unblinding. If the site and Botanix agree 
that unblinding is in the best interests of the subject, the IWRS system will be used to obtain 
treatment assignment information. The Medical Monitor must be notified whenever study 
medication is unblinded, preferably prior to unblinding a subject. 
5. EFFICACY AND SAFETY ENDPOINTS 
5.1 
Efficacy Endpoints 
5.1.1 
Primary Efficacy Endpoints 
The primary efficacy endpoint for the study is: 
• The proportion of subjects with Investigator Global Assessment (IGA) success defined as 
an IGA score of “Clear” (0) or “Almost Clear” (1) with at least a 2-grade improvement 
from Baseline at Day 85 


 
 
 
 
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5.1.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints for the study are: 
• The change from Baseline in the total Signs of AD score at Day 85, 
• The proportion of subjects with an IGA of Clear or Almost Clear at Day 85, 
• The proportion of subjects with at least a 2-grade improvement in IGA from Baseline at 
Day 85, 
• The change from Baseline in the percent of total body surface area (BSA) affected by AD 
at Day 85, 
• The time to achieve IGA success, and 
• The change from Baseline to Day 85 in the Itch-Numerical Rating Scale (I-NRS). 
5.1.3 
Exploratory Efficacy Endpoints 
The exploratory endpoints for the study are: 
• The change from Baseline in the total Signs of AD score at Day 15, Day 29, and Day 57, 
• The change from Baseline in the percent of total BSA affected by AD at Day 15, Day 29, 
and Day 57 
• The proportion of subjects with IGA success defined as an IGA score of “Clear: (0) or 
“Almost Clear” (1) with at least a 2-grade improvement from Baseline at Day 15, Day 
29, and Day 57, 
• The change from Baseline to Day 29 and Day 57, and Day 85 in the Signs of AD score 
for the target lesion (at selected sites only). 
5.2 
Safety Endpoints 
Safety will be assessed through adverse events (AEs), complete blood count (CBC), chemistry, 
and urinalysis laboratory tests, and reports of burning/stinging obtained during visits on Day 1, 
Day 15, Day 29, Day 57, and Day 85 (within AEs). 


 
 
 
 
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6. STATISTICAL AND ANALYTICAL PLANS 
6.1 
General Methodology 
All statistical processing will be performed using SAS® 9.4 or higher. No interim analyses are 
planned. This Phase 2 study is designed to identify the response of BTX 1204 4.0% BID 
compared to Vehicle BID. Statistical tests will be exploratory. No adjustments for Type I error 
will occur. 
Descriptive statistics will be used to provide an overview of the efficacy and safety results. For 
categorical parameters, the number and percentage of subjects in each category will be 
presented. For continuous parameters, descriptive statistics will include n (number of subjects), 
mean, standard deviation (SD), median, minimum and maximum.  
The primary method of handling missing efficacy data in the Intent-to-Treat (ITT) and modified 
Intent-to-Treat (mITT) analysis sets will be based on last observation carried forward (LOCF). 
Repeated measures analyses will be used on the observed data as a sensitivity analysis on the 
primary endpoint. 
The efficacy analysis performed on the ITT population is considered the primary analysis. The 
efficacy analyses performed on the mITT and per-protocol (PP) populations are considered 
supportive analyses. 
The number of subjects in each analysis set will be summarized. Reasons for study withdrawal 
during the study will be summarized using frequencies and percentages by treatment group. 
Reported AEs, medical history terms and prior and concomitant procedures and therapies will be 
classified on the basis of Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
Prior and concomitant medications will be classified on the basis of World Health Organization 
Drug Dictionary (WHO-DDE) terminology. 
6.1.1 
Statistical Analysis 
All analyses will be performed by QST using SAS® Version 9.4 or later. All summary tables 
and data listings will be prepared utilizing SAS® software. 
The standard operating procedures of QST will be followed in the creation and quality control of 
all data displays and analyses. 
6.1.2 
Baseline Definition 
Baseline is defined as the last non-missing assessment prior to first application of study drug.  


 
 
 
 
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6.1.3 
Visit Windowing 
Data will be summarized based on nominal visit indications with the exception of data captured 
at early termination and unscheduled visits. Data from early termination and unscheduled visits 
will be summarized based on mapped visit values. The analysis windows for early termination 
and unscheduled visits are presented in the following table.  
Analysis Windows for Efficacy and Safety Assessments 
Scheduled Visit 
Target Study Day 
Window (Days) 
Day 15 
15 
9 to 21 
Day 29 
29 
22 to 42 
Day 57 
57 
43 to 70 
Day 85 
85 
71 to 98 
 
Data collected at early termination and unscheduled visits prior to study day 9 will not be 
analyzed, with the exception of those identified as Baseline values. Efficacy and safety data 
collected at early termination and unscheduled visits after study day 98 will not be included in 
analyses.  
The definition for the study day included in each study window is defined as below: 
 
Study Day prior to Day 1 = Visit Date – Day 1 Date 
 
Study Day on or after Day 1 = Visit Date – Day 1 Date + 1 
If an assessment’s mapped visit is a visit at which the subject has data from a scheduled visit 
present, or if no analyses are planned for the assessment at the mapped visit, the data collected at 
the early termination or unscheduled visit will not be included in analyses.  
In the event of multiple values from unscheduled or early termination assessments within an 
analysis window, the value closest to the scheduled visit target study day will be used for 
analyses. If two values tie as closest to the time point (for example, one value is before and the 
other value is after the time point), then the later value will be selected.  
Data collected at all visits will be included in the data listings with visit presented as reported by 
the site. 


 
 
 
 
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6.1.4 
Adjustments for Covariates 
Baseline total BSA affected by AD will be a covariate for the secondary efficacy endpoint, 
change from Baseline in total BSA affected by AD. Baseline Signs of AD total score will be a 
covariate for the secondary and exploratory efficacy endpoints change from Baseline in total 
Signs of AD. No other covariates are planned to be used in the analyses for this study.  
6.1.5 
Handling of Dropouts or Missing Data 
All efforts will be made to minimize the occurrence of missing data. It is not expected that 
dropout rates will differ between groups. Therefore, the primary method of handling missing 
efficacy data in the ITT and mITT analysis set will be based on LOCF. Summary of efficacy 
variables for the PP subjects will be based on available data. No imputation will be done for non-
efficacy related variables.  
If a partial date is reported where the day is missing, then the day will be imputed as the first day 
of the month unless the month is the same month as the first application of study drug then the 
day will be that of first application with the month and year remaining the same. If a partial date 
is reported where the month is missing, then the month will be imputed to January unless the 
year is the same year as the first application of study drug then the month will be that of first 
application with the year remaining the same. If a partial date where both the day and month is 
missing, follow details as stated previously.  
Missing AE start dates will be imputed using partial date imputation rules as previously 
described in this Section. 
6.1.6 
Interim Analyses and Data Monitoring 
No interim analysis or data monitoring is planned for this study. Blinded subject data will be 
reviewed as it is generated to monitor for any safety signals and to ensure that the study is being 
appropriately executed. 
6.1.7 
Multicenter Studies 
This study will be conducted at multiple investigational sites in the United States (US), Australia 
(AUS) and New Zealand (NZ) with the intention of pooling the results for analysis. 


 
 
 
 
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6.1.8 
Multiple Comparisons/Multiplicity 
This Phase 2a study is designed to identify the response to BTX 1204 relative to vehicle. 
Statistical tests applied to the outcomes will be exploratory. No adjustments for Type 1 error will 
occur. 
6.1.9 
Use of an Efficacy Subset of Subjects 
One subset of interest is the mITT population. This subset is defined in order to better assess the 
effects of treatment on target areas; see Section 6.4.3 for definition. 
Subjects randomized to study drug who complete the Day 85 visit without noteworthy study 
protocol violations, including compliance with study drug application, and completion of 
efficacy evaluations on Day 85 will form the PP population. Any noteworthy protocol violations 
will be defined at the time of evaluability evaluation, the time between the database soft lock and 
hard lock before unblinding.  
Both mITT and PP analyses will allow for a further exploration of overall efficacy of BTX 1204. 
6.1.10 
Active-Control Studies Intended to Show Equivalence 
Not applicable to this study. 
6.1.11 
Examination of Subgroups 
Subset analyses will be conducted for the mITT and PP analysis sets on the primary efficacy 
endpoint. These analyses will be summarized using descriptive statistics. The specific subsets 
within the mITT and PP analysis sets that will be evaluated include: 
• Geographical region (US vs AUS/NZ); 
• Gender (Male vs. Female); 
• Ethnicity (Hispanic or Latino vs Non-Hispanic or Latino); 
• Race (White vs Non-White) 
• Age (12 to < 18 Years vs. 18 to < 30 Years vs. ≥30 Years) 
6.2 
Disposition of Subjects 
The number of subjects included in each analysis population (randomized, ITT, mITT, safety, 
PP) will be summarized by treatment group. The number of subjects completed, and 


 
 
 
 
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discontinued (including the primary reasons for discontinuation) will be summarized for each 
treatment group. 
Subjects who are excluded from an analysis population will be summarized by the primary 
reasons for exclusion. 
6.3 
Protocol Deviations 
Protocol deviations will not be entered into the database. Deviations leading to exclusion from 
analysis populations will be identified and summarized. 
6.4 
Data Sets Analyzed 
6.4.1 
Randomized Population 
All subjects who are randomized to study treatment will be included in the randomized 
population and will be analyzed according to the treatment group they were randomized. Listings 
and summaries will be provided for all randomized subjects. 
6.4.2 
Intent-to-Treat Population 
All subjects in the randomized population who receive at least one application of study drug and 
have at least one post-Baseline efficacy assessment will be included in the ITT population and 
analyzed according to the randomized treatment group. All efficacy analyses will be presented 
using the ITT population. 
6.4.3 
Modified Intent-to-Treat Population 
All subjects in the ITT population with no new areas of AD post-Baseline compared to Baseline 
BSA areas of AD will be included in the mITT population and analyzed according to the 
randomized treatment group. All efficacy analyses will be presented using the mITT population 
as supportive. 
6.4.4 
Safety Population 
All subjects who receive at least one application of study drug and have at least one post-
Baseline safety assessment will be included in the Safety population and analyzed according to 
the treatment received. All safety analyses will be performed using the Safety population. 


 
 
 
 
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6.4.5 
Per-Protocol Population 
All subjects in the ITT population who complete the Day 85 visit without noteworthy study 
protocol violations will be included in the PP population and analyzed according to the treatment 
group received. The PP population will include subjects in the ITT population who do not meet 
any of the following criteria: 
• Violated the inclusion/exclusion criteria; 
• Have taken any interfering concomitant medication; 
• Has missing IGA assessment at the Day 85 visit; 
• Have missed both the Day 29 and Day 57 visits; 
• Have not been compliant with the dosing regimen (i.e. subjects must apply 80 – 120% of 
the expected applications of study medication during participation in the study); 
• Out of visit window at the Day 85 visit by ±7 days; 
Subjects that discontinue from the study due to an AE related to study treatment or documented 
lack of treatment effect will be included in the PP population. Prior to breaking the blind, other 
additional criteria may be added to the list to accommodate for unforeseen events that occurred 
during the conduct of the trial that result in noteworthy study protocol violations. 
All efficacy analyses will be performed on the PP population with results considered as 
supportive. 
6.5 
Demographic and Other Baseline Characteristics 
All Baseline summaries will be done on the ITT, mITT, PP, and Safety populations. 
Sex, race, and ethnicity will be summarized by counts and percentages. Age, height (cm), and 
weight (kg) will be summarized with descriptive statistics. 
Baseline total BSA affected by AD and duration of AD will be summarized with descriptive 
statistics. Baseline IGA will be summarized by counts and percentages. 
The duration of AD will be calculated as follows: 
 
Duration of AD = year of Baseline visit – year of AD diagnosis + 1. 
Medical histories will be coded using the MedDRA dictionary and presented in a by-subject 
listing. 


 
 
 
 
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6.6 
Prior and Concomitant Medications 
Concomitant medications will be coded to preferred name and Anatomical Therapeutic Chemical 
(ATC) classification of ingredients using the WHO-DDE terminology. 
Counts and percentages will be provided to summarize the use of concomitant medications other 
than the study drug reported throughout the study. The number and percent of subjects who took 
other therapy will be shown by ATC level 2 term and preferred name. Medications which start 
prior to first application will be considered prior medications. Ongoing medications and 
medications ending after the date of first application will be considered concomitant 
medications. Incomplete start and end dates which could be either prior to first application or 
after first application will be considered prior to first application. 
A by-subject listing of all prior and concomitant medications will be presented. 
6.7 
Concomitant Antibiotic Therapies 
Concomitant antibiotic therapies will be determined by Botanix prior to database lock. 
Counts and percentages will be provided to summarize the use of concomitant antibiotic 
therapies reported throughout the study. The number and percent of subjects who took 
concomitant therapies will be shown by ATC level 2 term and preferred name. 
A by-subject listing of all concomitant antibiotic therapies will be presented. 
6.8 
Analysis of Efficacy 
The efficacy analyses will be performed using the ITT (primary), mITT (supportive), and PP 
(supportive) populations. The IGA, total BSA affected by AD, Signs of AD total score, and I-
NRS analyses will employ the methods for handling missing data as described in Section 6.1.5. 
IGA, total BSA affected by AD, Signs of AD score, and I-NRS data will also be shown in by-
subject listings. 
6.8.1 
Primary Efficacy Analysis 
The proportion of subjects with IGA success defined as an IGA score of Clear (0) or Almost 
Clear (1) with at least a 2-grade improvement from Baseline at Day 85 will be analyzed using 
logistic regression with a term for treatment. 


 
 
 
 
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6.8.2 
Secondary Efficacy Analysis 
6.8.2.1 
Signs of Atopic Dermatitis at Day 85 
The Signs of AD total score will be calculated based on the sum of the score for each component 
(erythema, exudation, excoriation, induration/papulation, and lichenification). Each component 
will be scored as 0, 1, 2, or 3. The total score therefore ranges from 0 to a maximum score of 15. 
The change from Baseline to Day 85 in the total Signs of AD score will be analyzed using 
analysis of covariance (ANCOVA) with Baseline Signs of AD as covariate and treatment as a 
factor.  
6.8.2.2 
Proportion of Subjects with an IGA of Clear (0) or Almost Clear (1) at Day 
85 
The proportion of subjects with an IGA of Clear (0) or Almost Clear (1) at Day 85 will be 
analyzed analogously to the primary endpoint. 
6.8.2.3 
Proportion of Subjects with at least a 2-Grade Improvement in IGA at Day 
85 
The proportion of subjects with at least a 2-grade improvement from Baseline at Day 85 will be 
analyzed analogously to the primary endpoint. 
6.8.2.4 
Percent of Total Body Surface Area Affected by Atopic Dermatitis at Day 85 
The change from Baseline to Day 85 in percent of total BSA affected by AD will be analyzed 
using ANCOVA with Baseline total BSA affected by AD as covariate and treatment as a factor. 
6.8.2.5 
Time to Achieve IGA Success 
Time to achieve IGA success will be summarized using the Kaplan-Meier method and displayed 
graphically. Medians, as well as 25% and 75% percentiles will be presented. Elapsed times will 
be computed from the date of first dose to the date of IGA assessment. Subjects not achieving the 
event by the time of completion/discontinuation will be right censored using the date of the last 
recorded non-missing assessment. 
6.8.2.6 
I-NRS at Day 85 
The change from Baseline to Day 85 in the I-NRS score will be summarized with descriptive 
statistics. 


 
 
 
 
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Summary statistics will also be presented for the change from Baseline in I-NRS at each 
timepoint (Day 15, Day 29, Day 57 and Day 85). Additionally, summary statistics for I-NRS will 
be presented at each timepoint (Baseline, Day 15, Day 29, Day 57 and Day 85). 
6.9 
Exploratory Efficacy Analysis 
6.9.1.1 
Signs of Atopic Dermatitis at Days 15, 29 and 57 
The change from Baseline in the Signs of AD total score for the target lesion at Day 15, Day 29, 
and Day 57 will be analyzed using ANCOVA with Baseline score as a covariate and treatment as 
a factor. 
Summary statistics will also be presented for the change from Baseline in each of the Signs of 
AD scores (erythema, exudation, excoriation, induration/papulation, and lichenification) and 
total score at each timepoint (Day 15, Day 29, Day 57 and Day 85). 
Summary statistics for each of the Signs of AD scores (erythema, exudation, excoriation, 
induration/papulation, and lichenification) and total score at each timepoint will be presented 
(Baseline, Day 15, Day 29, Day 57 and Day 85). 
6.9.1.2 
Percent of Total Body Surface Area Affected by Atopic Dermatitis at Days 
15, 29 and 57 
Change from Baseline in the percent of total BSA affected by AD at Days 15, 29, and 57 will be 
analyzed using ANCOVA with Baseline percent of total BSA affected by AD as covariate and 
treatment as factor. 
Summary statistics will be presented for the percent of total BSA affected by AD and change 
from Baseline at each timepoint (Day 15, Day 29, Day 57 and Day 85). 
6.9.1.3 
Investigator Global Assessment at Days 15, 29 and 57 
The proportion of subjects with IGA success defined as an IGA score of Clear (0) or Almost 
Clear (1) with at least a 2-grade improvement from Baseline at Day 15, Day 29, and Day 57 will 
be analyzed using the same logistic regression method described for the primary endpoint. 
Summary statistics by IGA Score at each timepoint (Baseline, Day 15, Day 29, Day 57 and Day 
85) and dichotomized IGA at each post-Baseline timepoint (Day 15, Day 29, Day 57 and Day 
85) will also be presented at each post-Baseline timepoint. 


 
 
 
 
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6.9.1.4 
Signs of Atopic Dermatitis at Target Lesions (at selected photography sites 
only) at Days 29, 57 and 85 
At selected sites, a target lesion will be identified, photographed and scored with the Signs of 
AD. 
The change from Baseline to Day 29, and Day 57, and Day 85 Signs of AD total score at target 
lesions will be analyzed using an ANCOVA with Baseline score as a covariate and treatment as a 
factor. 
Summary statistics for each of the Signs of AD scores (erythema, exudation, excoriation, 
induration/papulation, and lichenification) and total score at target lesions for each timepoint will 
be presented (Baseline, Day 15, Day 29, Day 57 and Day 85). 
6.10 
Sensitivity Analyses 
The sensitivity analyses will be performed using the ITT population.  
6.10.1 
Repeated Measures 
The first sensitivity analysis for the primary endpoint, IGA success, will be analyzed using a 
repeated measures logistic regression (generalized estimating equations), with dichotomized IGA 
success as the dependent variable and treatment group, visit, and treatment group by visit 
interaction as independent factors. In this analysis, data from all post-Baseline visits will be 
included with no imputation for missing data. 
proc genmod data = datain; 
class SUBJECT TRT VISIT; 
model IGA SUCCESS = TRT VISIT TRT * VISIT / dist=bin; 
repeated subject = SUBJECT/type = cs; 
lsmeans TRT*VISIT / diff; 
estimate ‘pval’ TRT 1 -1 TRT*VISIT 0 0 1 0 0 -1; 
run; 
6.10.2 
Tipping Point 
A tipping point analysis of the primary endpoint, proportion of subjects with IGA success 
defined as an IGA score of Clear (0) or Almost Clear (1) with at least a 2-grade improvement 
from Baseline at Day 85, will be performed as a sensitivity analysis for the handling of missing 
data. Specifically, a range of response rates for both groups will be explored to determine the 
tipping point(s) at which the combinations result in no longer reaching statistical significance. 


 
 
 
 
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6.11 
Safety Evaluation 
6.11.1 
Extent of Exposure 
The extent of exposure to study drug in each treatment group will be summarized by total 
number of applications, number of missed applications, number and percentage of subjects who 
are compliant, and amount of drug used total.  Exposure and compliance will not be calculated 
for subjects who are lost to follow-up. A subject will be considered compliant with the dosing 
regimen if the subject applies 80% to 120% of the expected number of applications while 
enrolled in the study. 
 
The total amount of study drug used will be calculated from the drug accountability record using 
the recorded weights for subjects with an initial weight and return weight for all dispensed 
pumps of study drug. The difference between the dispensed weight and the returned weight for 
each pump will be summed over all pumps to calculate the total amount of study drug used.  
Compliance will be calculated based on the applications of study drug. The total number of 
applications is as follows: 
If 2 applications expected on Date of Last Application: 2*(Date of Last Application - 
Date of First Application + 1) – (Number of doses marked as missed on the CRF). 
 
If 1 application expected on Date of Last Application: 2*(Date of Last Application - Date 
of First Application) +1 – (Number of doses marked as missed on the CRF). 
 
The total number of applications expected is as follows: 
 
 
2*(Date Subject Ended Participation - Date of Randomization + 1). 
 
If the total number of applications exceeds 178 then it will set to 178. 
 
Compliance will be calculated as a percentage as 100 times the total number of applications 
taken divided by the total number of applications expected while enrolled in the study. 
6.11.2 
Adverse Events 
All AEs that occur during the study will be recorded and classified on the basis of Medical 
Dictionary for Regulatory Activities (MedDRA) terminology. Treatment-emergent AEs 
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Adverse events noted prior to the first study drug administration that worsen after Baseline will 
also be reported as AEs and included in the summaries. Burning/stinging is a pre-defined safety 
endpoint; subjects’ reports of burning/stinging will be reported as AEs and included in a separate 
summary. 
An overall summary of TEAEs will be presented showing the number of subjects reporting at 
least one TEAE, number reporting at least one serious adverse event (SAE), number reporting at 
least one TEAE leading to study discontinuation, and number of TEAEs by severity and by 
relationship for each treatment group. The total number of AEs will also be presented as part of 
the overall summary of TEAEs. Treatment-emergent AEs will be summarized by system organ 
class and preferred name. Serious TEAEs, Related TEAEs, Severe TEAEs, and TEAEs leading 
to study discontinuation will also be summarized by system organ class and preferred name. 
A summary of time until study discontinuation for subjects who discontinue due to a TEAE will 
also be presented. 
In addition, a listing of all AEs, a listing of Serious AEs, and a listing of subjects who 
prematurely discontinue from the study due to an AE will be provided. A summary of subjects 
who discontinue the study due to AEs will be included. 
No statistical inference between treatments will be performed on AEs. 
6.11.3 
Drug Abuse and Liability Assessments 
Adverse events associated with potential abuse or overdose will be recorded and classified by 
MedDRA System Organ Classifications (SOC) and MedDRA Preferred Terms (PTs) as outlined 
in the Safety Management Plan. The incidence of abuse related AEs will be summarized by 
treatment group using frequency counts and percentages. 
A by-subject listing of abuse related AEs will also be presented. 
6.11.4 
Clinical Laboratory Evaluation 
Laboratory test results will be summarized with descriptive statistics at Baseline and Day 85. 
Additionally, shifts from Baseline to Day 85 in laboratory test results based on normal ranges 
will be summarized with frequency counts and percentages. Individual laboratory test results will 
be presented in a by-subject listing. A by-subject listing of abnormal lab findings will also be 
provided. 


 
 
 
 
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6.11.5 
Other Observations Related to Safety 
6.11.5.1 
Physical Examination 
Physical examination (review of systems) data will be presented in a by-subject listing. 
7. DETERMINATION OF SAMPLE SIZE 
The sample size for this study is based on clinical considerations only. Subjects will be 
randomized 1:1 with 100 subjects in each treatment group for a total 200 subjects. This is 
considered adequate to evaluate the safety and tolerability and preliminary information on 
efficacy of twice daily BTX 1204 4% in the treatment of moderate atopic dermatitis in subjects 
aged 12 to 70 years of age. 
8. CHANGES IN THE PLANNED ANALYSES 
Baseline IGA will not be used as a factor for the primary, secondary, and exploratory efficacy 
IGA endpoints as treatment was not stratified by IGA score. 
The ITT population was updated to specify inclusion only of subjects with at least one post-
Baseline efficacy assessment. 
The mITT population was added to the SAP in order to assess efficacy for subjects with 
consistent areas of AD lesions. 
A tipping point analysis was added as an additional sensitivity analysis on the ITT population. 
 
 


 
 
 
 
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9. REFERENCES 
1. Ben-Shabat S, Hanus LO, Katzavian G, Gallily R. New cannabidiol derivatives: 
synthesis, binding to cannabinoid receptor, and evaluation of their antiinflammatory 
activity. J Med Chem. 2006; 49:1113-1117. 
 
2. Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of 
inflammation on oxidative stress. Free Radic Biol Med. 2011; 51:1054-1061. 
 
3. De Filippis D, Esposito G, Cirillo C, Cipriano M, De Winter BY, Scuderi C et al. 
Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis. 
PLoS One. 2011; 6:e28159 [8pp]. 
 
4. Fouad AA, Jresat I. Therapeutic potential of cannabidiol against ischemia/reperfusion 
liver injury in rats. Eur J Pharmacol. 2011; 670:216-223. 
 
5. Fouad AA, Al-Mulhim AS, Jresat I. Cannabidiol treatment ameliorates 
ischemia/reperfusion renal injury in rats. Life Sci. 2012; 91:284-292. 
 
6. Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic 
diseases. Expert Rev Clin Immunol. 2017; 13:425-437. 
 
7. Giacoppo S, Galuppo M, Pollastro F, Grassi G, Bramanti P, Mazzon E. A new 
formulation of cannabidiol in cream shows therapeutic effects in a mouse model of 
experimental autoimmune encephalomyelitis. Daru. 2015; 23:48. 
 
8. Guttman-Yassky E, Krueger JG, Lebwohl MG. Systemic immune mechanisms in atopic 
dermatitis and psoriasis with implications for treatment. Exp Dermatol. 2017 [Epub 
ahead of print – Mar. 7, 2017]. 
 
9. Kozela E, Juknat A, Kaushansky N, Ben-Nun A, Coppola G, Vogel Z. Cannabidiol, a 
non-psychoactive cannabinoid, leads to EGR2-dependent anergy in activated 
encephalitogenic T cells. J Neuroinflammation. 2015; 12:52 [16pp]. 
 
10. Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene 
networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, 
in autoimmune T cells. J Neuroinflammation. 2016; 13:136 [19pp]. 
 
11. Lee W-S, Erdelyi K, Matyas C, Mukhopadhyay P, Varga ZV, Liaudet L et al. 
Cannabidiol limits T cell-mediated chronic autoimmune myocarditis: implications to 
autoimmune disorders and organ transplantation. Mol Med. 2016; 22:136-146. 
 


 
 
 
 
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12. Mukhopadhyay P, Rajesh M, Horváth B, Bátkai S, Park O, Tanchian G et al. Cannabidiol 
protects against hepatic ischemia/reperfusion injury by attenuating inflammatory 
signaling and response, oxidative/nitrative stress, and cell death. Free Radic Biol Med. 
2011; 50:1368-1381. 
 
13. National Eczema Organization. Understanding Your Atopic Dermatitis. San Rafael (CA): 
National Eczema Organization; 2017. Available at: 
https://nationaleczema.org/eczema/types-of-eczema/atopic-dermatitis/ [Last accessed: 
June 16, 2017]. 
 
14. Nowicki R, Trzeciak M, Wilkowska A, Sokolowska-Wojdylo M, Lugowska-Umer H, 
Baranska-Rybak W et al. Atopic dermatitis: current treatment guidelines. Statement of 
the experts of the Dermatological Section, Polish Society of Allergology, and the 
Allergology Section, Polish Society of Dermatology. Postepy Dermatol Alergol. 2015; 
32:239-249. 
 
15. Olah A, Toth B, Borbiro I, et al, Cannabidiol exerts sebostatic and anti-inflammatory 
effects on human sebocytes, J Clin Invest 2014; 124(9); 3713-3724 
 
16. Petrosino S, Verde R, Vaia M, Allarà M, Iuvone T, Di Marzo V (2018): Anti-
inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in 
Experimental Allergic Contact Dermatitis. J Pharmacol Exp Ther. 365(3): 652-663. 
 
17. Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation 
through a non-CB1/CB2 mechanism and have a potential therapeutic value in the 
treatment of psoriasis. J Dermatol Sci. 2007; 45:87-92. 
 


 
 
 
 
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10. INDEX OF PLANNED TABLES 
Table 14.0.1: Summary of Subject Completion/Discontinuation (Randomized Subjects) ...........31 
Table 14.0.2: Summary of Subjects Excluded from Analyses (Randomized Subjects) ................32 
Table 14.0.3: Summary of Reasons for Screen Failure (Non-Randomized Subjects)...................34 
Table 14.1.1.1: Summary of Subject Demographics (ITT Population) .........................................35 
Table 14.1.1.2: Summary of Subject Demographics (mITT Population) ......................................36 
Table 14.1.1.3: Summary of Subject Demographics (PP Population) ...........................................36 
Table 14.1.1.4: Summary of Subject Demographics (Safety Population) .....................................36 
Table 14.1.2.1: Summary of Baseline Characteristics (ITT Population) .......................................37 
Table 14.1.2.2: Summary of Baseline Characteristics (mITT Population)....................................39 
Table 14.1.2.3: Summary of Baseline Characteristics (PP Population) ........................................39 
Table 14.1.2.4: Summary of Baseline Characteristics (Safety Population) ...................................39 
Table 14.1.3.1: Summary of Concomitant Medications by ATC Level 2 Term and Preferred 
Name (ITT Population) .........................................................................40 
Table 14.1.3.2: Summary of Concomitant Medications by ATC Level 2 Term and Preferred 
Name (mITT Population) ......................................................................41 
Table 14.1.3.3: Summary of Concomitant Medications by ATC Level 2 Term and Preferred 
Name (PP Population) ...........................................................................41 
Table 14.1.3.4: Summary of Concomitant Medications by ATC Level 2 Term and Preferred 
Name (Safety Population) .....................................................................41 
Table 14.1.4.1: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and 
Preferred Name (ITT Population) .........................................................42 
Table 14.1.4.2: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and 
Preferred Name (mITT Population) ......................................................43 
Table 14.1.4.3:  Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and 
Preferred Name (PP Population) ...........................................................43 
Table 14.1.4.4: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and 
Preferred Name (Safety Population) .....................................................43 
Table 14.2.1.1: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85  (ITT 
Population) ............................................................................................44 
Table 14.2.1.2: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 (mITT 
Population) ............................................................................................45 


 
 
 
 
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Table 14.2.1.3: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 (PP 
Population) ............................................................................................45 
Table 14.2.1.4: Sensitivity Analysis of Primary Efficacy Endpoint: Dichotomized IGA Success 
at Day 85  (ITT Population) ..................................................................46 
Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 
85  (mITT Population) ..........................................................................47 
Table 14.2.1.7: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 
85 (PP Population) ................................................................................52 
Table 14.2.2.1.1: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 
85  (ITT Population)..............................................................................53 
Table 14.2.2.1.2: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 
85 (mITT Population) ...........................................................................54 
Table 14.2.2.1.3: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 
85 (PP Population) ................................................................................54 
Table 14.2.2.2.1: Secondary Endpoint: Dichotomized IGA at Day 85  (ITT Population) ............55 
Table 14.2.2.2.2: Secondary Endpoint: Dichotomized IGA at Day 85 (mITT Population) ..........56 
Table 14.2.2.2.3: Secondary Endpoint: Dichotomized IGA at Day 85 (PP Population) ...............56 
Table 14.2.2.3.1: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Day 85  (ITT Population) ......................................................57 
Table 14.2.2.3.2: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Day 85 (mITT Population) ....................................................58 
Table 14.2.2.3.3: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Day 85 (PP Population) .........................................................58 
Table 14.2.2.4.1: Secondary Endpoint: Time to IGA Success (ITT Population) ..........................59 
Table 14.2.2.4.2: Secondary Endpoint: Time to IGA Success (mITT Population) .......................60 
Table 14.2.2.4.3: Secondary Endpoint: Time to IGA Success (PP Population) ............................60 
Table 14.2.2.5.1: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit 
(ITT Population)....................................................................................61 
Table 14.2.2.5.2: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit 
(mITT Population) ................................................................................64 
Table 14.2.2.5.2: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit (PP 
Population) ............................................................................................64 
Table 14.2.3.1.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Days 15, 29 and 57  (ITT Population) ..................................................65 


 
 
 
 
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Table 14.2.3.1.2: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Days 15, 29 and 57 (mITT Population) ................................................67 
Table 14.2.3.1.3: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Days 15, 29 and 57 (PP Population) .....................................................67 
Table 14.2.3.2.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit (ITT 
Population) ............................................................................................68 
Table 14.2.3.2.2: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit 
(mITT Population) ................................................................................70 
Table 14.2.3.2.3: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit (PP 
Population) ............................................................................................70 
Table 14.2.3.3.1: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Days 15, 29 and 85  (ITT Population) ...................................71 
Table 14.2.3.3.2: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Days 15, 29 and 85 (mITT Population) .................................73 
Table 14.2.3.3.3: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected 
by AD at Days 15, 29 and 85 (PP Population) ......................................73 
Table 14.2.3.4.1: Summary of Percent of Total BSA Affected by AD by Visit (ITT 
Population) ............................................................................................74 
Table 14.2.3.4.2: Summary of Percent of Total BSA Affected by AD by Visit (mITT 
Population) ............................................................................................77 
Table 14.2.3.4.3: Summary of Percent of Total BSA Affected by AD by Visit (PP Population) .77 
Table 14.2.3.5.1: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at 
Days 15, 29 and 57  (ITT Population) ..................................................78 
Table 14.2.3.5.2: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at 
Days 15, 29 and 57 (mITT Population) ................................................79 
Table 14.2.3.5.3: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at 
Days 15, 29 and 57 (PP Population) .....................................................79 
Table 14.2.3.6.1: Summary of Investigator Global Assessment by Visit (ITT Population) ..........80 
Table 14.2.3.6.2: Summary of Investigator Global Assessment by Visit (mITT Population) ......84 
Table 14.2.3.6.3: Summary of Investigator Global Assessment by Visit (PP Population) ...........84 
Table 14.2.3.7.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Target Lesions at Days 29, 57 and 85  (ITT Population) ......................85 
Table 14.2.3.7.2: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Target Lesions at Days 29, 57 and 85 (mITT Population) ....................87 


 
 
 
 
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Table 14.2.3.7.3: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at 
Target Lesions at Days 29, 57 and 85 (PP Population).........................87 
Table 14.2.3.8.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target 
Lesions by Visit (ITT Population) ........................................................88 
Table 14.2.3.8.2: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target 
Lesions by Visit (mITT Population) .....................................................90 
Table 14.2.3.8.3: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target 
Lesions by Visit (PP Population) ..........................................................90 
Table 14.3.0.1: Summary of Extent of Exposure (Safety Population) ..........................................91 
Table 14.3.1.1: Summary of Treatment-Emergent Adverse Event Characteristics (Safety 
Population) ............................................................................................93 
Table 14.3.1.2: Summary of Treatment-Emergent Adverse Event by MedDRA System Organ 
Class and Preferred Term (Safety Population)......................................94 
Table 14.3.1.3: Summary of Serious Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term (Safety Population)...........................95 
Table 14.3.1.4: Summary of Related Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term (Safety Population)...........................95 
Table 14.3.1.5: Summary of Severe Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term (Safety Population)...........................95 
Table 14.3.1.6: Summary of Treatment-Emergent Adverse Events Leading to Study 
Discontinuation by MedDRA System Organ Class and Preferred Term 
(Safety Population)................................................................................95 
Table 14.3.1.7: Summary of Time to Study Discontinuation for Subjects Who Discontinue Due 
to Treatment-Emergent Adverse Events (ITT Population) ...................96 
Table 14.3.1.8: Summary of Treatment-Emergent Abuse-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term (Safety Population) ..............97 
Table 14.3.2.1.1: Summary of Chemistry Results by Visit (Safety Population) ...........................98 
Table 14.3.2.1.2: Shift Table for Chemistry Results (Safety Population) .....................................99 
Table 14.3.2.2.1: Summary of CBC Results by Visit (Safety Population) ..................................100 
Table 14.3.2.2.2: Shift Table for CBC Results (Safety Population) ............................................100 
Table 14.3.2.3.1: Summary of Numeric Urinalysis Results by Visit (Safety Population) ..........100 
Table 14.3.2.3.2: Shift Table for Numeric Urinalysis Results (Safety Population) ....................100 
Table 14.3.2.3.3: Summary of Character Urinalysis Results by Visit (Safety Population) .........101 


 
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Table 14.0.1: Summary of Subject Completion/Discontinuation 
(Randomized Subjects) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Completed Study 
xx ( xx.x%) 
xx ( xx.x%) 
Yes 
xx ( xx.x%) 
xx ( xx.x%) 
No 
Reason for Discontinuation from Study 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
Death 
xx ( xx.x%) 
xx ( xx.x%) 
Lost to Follow-Up  
xx ( xx.x%) 
xx ( xx.x%) 
Physician Decision 
xx ( xx.x%) 
xx ( xx.x%) 
Pregnancy  
xx ( xx.x%) 
xx ( xx.x%) 
Protocol Violation 
xx ( xx.x%) 
xx ( xx.x%) 
Study Terminated by Sponsor 
xx ( xx.x%) 
xx ( xx.x%) 
Withdrawal by Subject 
xx ( xx.x%) 
xx ( xx.x%) 
Worsening Condition 
xx ( xx.x%) 
xx ( xx.x%) 
Other 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.0.2: Summary of Subjects Excluded from Analyses 
(Randomized Subjects) 
(Page 1 of 2) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Number of Subjects Included in the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the ITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the ITT Population 
At Least One Post-Baseline Efficacy Assessment 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the mITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the mITT Population 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the mITT Populationa 
Not in the ITT Population  
xx ( xx.x%) 
xx ( xx.x%) 
No New Post-Baseline Areas of Atopic Dermatitisb  
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Included in the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the Safety Population 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the Safety Populationa 
No Evidence of Subject Dosing 
xx ( xx.x%) 
xx ( xx.x%) 
No Post Baseline Safety Assessment 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Table includes primary reason (assigned in order presented in table) subject was excluded. 
b The presence of new areas of atopic dermatitis were determined by post-baseline reports compared to baseline reports of BSA. 
c  See Listing 16.2.3 for a complete list of all other reasons for exclusion from the PP population. 
Note: The ITT exclusion of not being randomized is not presented as the table is on randomizied subjects. 
 
 Percentages are based on the number of randomized subjects. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.0.2: Summary of Subjects Excluded from Analyses 
(Randomized Subjects) 
(Page 2 of 2) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Number of Subjects Included in the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Subjects Excluded from the PP Population 
xx ( xx.x%) 
xx ( xx.x%) 
Reason for Exclusion from the PP Populationa 
Violated the Inclusion/Exclusion Criteria 
xx ( xx.x%) 
xx ( xx.x%) 
Received an Interfering Medication 
xx ( xx.x%) 
xx ( xx.x%) 
Missed Investigator Global Assessment at Day 85 
xx ( xx.x%) 
xx ( xx.x%) 
Missed Both Day 29 and Day 57 Visits 
xx ( xx.x%) 
xx ( xx.x%) 
Not Compliant with Dosing Regimen 
xx ( xx.x%) 
xx ( xx.x%) 
Day 85 Visit not within +/- 7 days Window 
xx ( xx.x%) 
xx ( xx.x%) 
Otherc 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Table includes primary reason (assigned in order presented in table) subject was excluded. 
b The presence of new areas of atopic dermatitis were determined by post-baseline reports compared to baseline reports of BSA. 
c  See Listing 16.2.3 for a complete list of all other reasons for exclusion from the PP population. 
Note: The ITT exclusion of not being randomized is not presented as the table is on randomizied subjects. 
 
 Percentages are based on the number of randomized subjects. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.0.3: Summary of Reasons for Screen Failure 
(Non-Randomized Subjects) 
 
  
Total 
 
(N=xx) 
 
Reason for Screen Failure 
  Adverse Event 
                          xx ( xx.x%) 
  Inclusion and/or Exclusion Criteria 
                          xx ( xx.x%) 
  Withdrawal by Subject 
                          xx ( xx.x%) 
  Withdrawal by Legally Authorized Representive  
                          xx ( xx.x%) 
 Lost to Follow-Up 
                          xx ( xx.x%) 
  Other 
                          xx ( xx.x%) 
 
 
Note: Percentages are based on the number of non-randomized subjects. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.1.1.1: Summary of Subject Demographics 
(ITT Population) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Age (years) 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
12 to < 18 Years 
xx ( xx.x%) 
xx ( xx.x%) 
   18 to < 30 Years  
xx ( xx.x%) 
xx ( xx.x%) 
≥ 30 Years 
xx ( xx.x%) 
xx ( xx.x%) 
Sex 
n 
xx 
xx 
Male 
xx ( xx.x%) 
xx ( xx.x%) 
Female 
xx ( xx.x%) 
xx ( xx.x%) 
Ethnicity 
n 
xx 
xx 
Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
Not Hispanic or Latino 
xx ( xx.x%) 
xx ( xx.x%) 
Race 
n 
xx 
xx 
American Indian or Alaska Native 
xx ( xx.x%) 
xx ( xx.x%) 
Asian 
xx ( xx.x%) 
xx ( xx.x%) 
Black or African American 
xx ( xx.x%) 
xx ( xx.x%) 
Native Hawaiian or Other Pacific Islander 
xx ( xx.x%) 
xx ( xx.x%) 
White 
xx ( xx.x%) 
xx ( xx.x%) 
Multiple/Other 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Percentages are based on the number of subjects in the ITT population with a non-missing response. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Repeat Table 14.1.1.1 for the following: 
 
Table 14.1.1.2: Summary of Subject Demographics (mITT Population) 
Programming note: Replace footnote with - Note: Percentages are based on the number of subjects in the mITT population with a non-missing response. 
 
Table 14.1.1.3: Summary of Subject Demographics (PP Population) 
Programming note: Replace footnote with - Note: Percentages are based on the number of subjects in the PP population with a non-missing response. 
 
Table 14.1.1.4: Summary of Subject Demographics (Safety Population) 
Programming note: Replace footnote with - Note: Percentages are based on the number of subjects in the Safety population with a non-missing response. 
 
 


 
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Table 14.1.2.1: Summary of Baseline Characteristics 
(ITT Population) 
(Page 1 of 2) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Height (cm) 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
Weight (kg) 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
Investigator Global Assessment 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild  
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Total Body Surface Area Affected by AD 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
 
 
a Duration of AD is calculated as year of Baseline visit – year of AD diagnosis. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.1.2.1: Summary of Baseline Characteristics 
(ITT Population) 
(Page 2 of 2) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Duration of AD (Years)a 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
 
 
a Duration of AD is calculated as year of Baseline visit – year of AD diagnosis + 1. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Repeat Table 14.1.2.1 for the following: 
 
Table 14.1.2.2: Summary of Baseline Characteristics (mITT Population) 
Table 14.1.2.3: Summary of Baseline Characteristics (PP Population) 
Table 14.1.2.4: Summary of Baseline Characteristics (Safety Population) 
 


 
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Table 14.1.3.1: Summary of Concomitant Medications by ATC Level 2 Term and Preferred Name 
(ITT Population)  
(Page 1 of x) 
 
ATC Level 2 Term 
Preferred Namea 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Subjects with at Least One Concomitant Medication Reported 
xx ( xx.x%) 
xx ( xx.x%) 
ATC Level 2 Term 1 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name 1 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name 2 
xx ( xx.x%) 
xx ( xx.x%) 
  … 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name x 
xx ( xx.x%) 
xx ( xx.x%) 
… 
 
 
a WHO-DDE, Format B2, Version xxxxx. 
Note: Concomitant medications are those used on or after the date of first application of study medication. 
 
Percentages are based on the number of subjects in each treatment group in the ITT population. 
 
Subjects are only counted once per ATC Level 2 Term and once per Preferred Name. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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CONFIDENTIAL 
Repeat Table 14.1.3.1 for the following: 
 
Table 14.1.3.2: Summary of Concomitant Medications by ATC Level 2 Term and Preferred Name (mITT Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the mITT population. 
 
Table 14.1.3.3: Summary of Concomitant Medications by ATC Level 2 Term and Preferred Name (PP Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the PP population. 
 
Table 14.1.3.4: Summary of Concomitant Medications by ATC Level 2 Term and Preferred Name (Safety Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the Safety population. 
 
 


 
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Table 14.1.4.1: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and Preferred Name 
(ITT Population)  
(Page 1 of x) 
 
ATC Level 2 Term 
Preferred Namea 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Subjects with at Least One Concomitant Antibiotic Therapy Reported 
xx ( xx.x%) 
xx ( xx.x%) 
ATC Level 2 Term 1 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name 1 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name 2 
xx ( xx.x%) 
xx ( xx.x%) 
  … 
xx ( xx.x%) 
xx ( xx.x%) 
  Preferred Name x 
xx ( xx.x%) 
xx ( xx.x%) 
… 
 
 
a WHO-DDE, Format B2, Version xxxxx. 
Note: Concomitant antibiotic therapies are those used on or after the date of first application of study medication. 
 
Percentages are based on the number of subjects in each treatment group in the ITT population. 
 
Subjects are only counted once per ATC Level 2 Term and once per Preferred Name. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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CONFIDENTIAL 
Repeat Table 14.1.4.1 for the following: 
 
Table 14.1.4.2: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and Preferred Name (mITT Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the mITT population. 
 
Table 14.1.4.3:  Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and Preferred Name (PP Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the PP population. 
 
Table 14.1.4.4: Summary of Concomitant Antibiotic Therapies by ATC Level 2 Term and Preferred Name (Safety Population) 
Programming note: Replace 3rd footnote with - Percentages are based on the number of subjects in each treatment group in the Safety population. 
 
 


 
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Table 14.2.1.1: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 
 (ITT Population) 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID  
 
(N=xxx) 
 
 
Treatment  
 
 
P-Valuea 
 
At Least a 2 Grade Improvement from 
Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
Successa 
  xx.x%  
  xx.x%  
  
x.xxx 
Failurea 
  xx.x% 
  xx.x% 
 
 
a Estimates and p-value from a logistic regression with a term for treatment group. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 45 of 141 
CONFIDENTIAL 
Repeat Table 14.2.1.1 for the following: 
 
Table 14.2.1.2: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 (mITT Population) 
 
Table 14.2.1.3: Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 (PP Population) 
Programming note: Replace last footnote with - Note: No imputations were made for missing data. 
 
 


 
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Table 14.2.1.4: Sensitivity Analysis of Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 
 (ITT Population) 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID  
 
(N=xxx) 
 
 
Treatment  
 
 
P-Valuea 
 
At Least a 2 Grade Improvement from 
Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
Successa 
  xx.x%  
  xx.x%  
  
x.xxx 
Failurea 
  xx.x% 
  xx.x% 
 
 
a Estimates and p-value from a repeated measures logistic regression with .factors of treatment group, visit and treatment group by visit interaction.  
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 
 (mITT Population) 
(Page 1 of 5) 
  
 
Geographical Region: US 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Geographical Region: AUS/NZ 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
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Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 
 (mITT Population) 
(Page 2 of 5) 
  
 
Gender: Male 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Gender: Female 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
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Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 
 (mITT Population) 
(Page 3 of 5) 
  
 
Ethnicity: Hispanic or Latino 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Ethnicity: Non-Hispanic or Latino 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
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Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 
 (mITT Population) 
(Page 4 of 5) 
  
 
Race: White 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Race: Non-White 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
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Table 14.2.1.6: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 
 (mITT Population) 
(Page 5 of 5) 
  
 
Age: 12 to < 18 Years 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Age: 18 to < 30 Years 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Age: ≥ 30 Years 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
n 
xx 
xx 
Success  
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
Note: No imputations were made for missing data. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 52 of 141 
CONFIDENTIAL 
Repeat Table 14.2.1.6 for the following: 
 
Table 14.2.1.7: Subgroup Summary of the Primary Endpoint: Dichotomized IGA Success at Day 85 (PP Population) 
 
 


 
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CONFIDENTIAL 
Table 14.2.2.1.1: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 85 
 (ITT Population) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total Signs of AD 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
LSMeana 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 54 of 141 
CONFIDENTIAL 
Repeat Table 14.2.2.1.1 for the following: 
 
Table 14.2.2.1.2: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 85 (mITT Population) 
 
Table 14.2.2.1.3: Secondary Endpoint: Change from Baseline in Signs of AD Total Score at Day 85 (PP Population) 
Programming note: Replace last footnote with - Note: No imputations were made for missing data. 
 
 


 
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CONFIDENTIAL 
Table 14.2.2.2.1: Secondary Endpoint: Dichotomized IGA at Day 85 
 (ITT Population) 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID  
 
(N=xxx) 
 
 
Treatment  
 
 
P-Valuea 
 
IGA Grade of 0 or 1 
n 
xx 
xx 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
Successa 
  xx.x% 
 
  xx.x% 
 
  
x.xxx 
Failurea 
  xx.x% 
  xx.x% 
At Least a 2 Grade Improvement from Baseline in 
IGA 
n 
xx 
xx 
Success 
xx ( xx.x%) 
xx ( xx.x%) 
Failure 
xx ( xx.x%) 
xx ( xx.x%) 
Successa 
  xx.x% 
 
  xx.x% 
 
  
x.xxx 
Failurea 
  xx.x% 
  xx.x% 
 
 
a Estimates and p-value from a logistic regression with a term for treatment group and adjusted for baseline IGA. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 56 of 141 
CONFIDENTIAL 
Repeat Table 14.2.2.2.1 for the following: 
 
Table 14.2.2.2.2: Secondary Endpoint: Dichotomized IGA at Day 85 (mITT Population) 
 
Table 14.2.2.2.3: Secondary Endpoint: Dichotomized IGA at Day 85 (PP Population) 
Programming note: Replace last footnote with - Note: No imputations were made for missing data. 
 
 


 
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Table 14.2.2.3.1: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Day 85 
 (ITT Population) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total BSA Affected by AD 
n 
xx 
xx 
Mean 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
Min., Max. 
xx, xx 
xx, xx 
LSMeana 
xx.x 
x.xxxa 
LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total BSA Affected by AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 58 of 141 
CONFIDENTIAL 
Repeat Table 14.2.2.3.1 for the following: 
 
Table 14.2.2.3.2: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Day 85 (mITT Population) 
 
Table 14.2.2.3.3: Secondary Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Day 85 (PP Population) 
Programming note: Replace last footnote with - Note: No imputations were made for missing data. 
 
 


 
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Table 14.2.2.4.1: Secondary Endpoint: Time to IGA Success 
(ITT Population) 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Subjects with a Non-Missing Post-Baseline IGA 
xx 
xx 
Subjects with IGA Successa 
xx ( xx.x%) 
xx ( xx.x%) 
Subjects Censored 
xx ( xx.x%) 
xx ( xx.x%) 
Time to IGA Successa (Days) 
Minimumb 
xx 
xx 
25th Percentilec 
xx.x 
xx.x 
50th Percentilec 
xx.x 
xx.x 
75th Percentilec 
xx.x 
xx.x 
Maximumb 
xx 
xx 
 
 
a IGA Success is defined as an IGA score of Clear or Almost Clear with at least a 2-grade improvement from baseline. 
b Observed time to event. 
c Estimated using Kaplan-Meier methods. 
Note: Elasped times are computed from the date of first dose to the date of IGA assessment. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
Programming note: Minimum and Maximum values are among subjects achieving the event. Censored subjects are not considered. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 60 of 141 
CONFIDENTIAL 
Repeat Table 14.2.2.4.1 for the following: 
 
Table 14.2.2.4.2: Secondary Endpoint: Time to IGA Success (mITT Population) 
Table 14.2.2.4.3: Secondary Endpoint: Time to IGA Success (PP Population) 
 
 


 
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Table 14.2.2.5.1: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit 
(ITT Population) 
(Page 1 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
How would you rate your average itch in the past 24 hours? 
Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
Day 15 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.2.2.5.1: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit 
(ITT Population) 
(Page 2 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
How would you rate your average itch in the past 24 hours? 
Day 29 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
Day 57 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.2.2.5.1: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit 
(ITT Population) 
(Page 3 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
How would you rate your average itch in the past 24 hours? 
Day 85 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 64 of 141 
CONFIDENTIAL 
Repeat Table 14.2.2.5.1 for the following: 
 
Table 14.2.2.5.2: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit (mITT Population) 
 
Table 14.2.2.5.2: Secondary Endpoint: Summary of Itching-Numerical Rating Score by Visit (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
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Table 14.2.3.1.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Days 15, 29 and 57 
 (ITT Population) 
(Page 1 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Signs of AD Total Score 
Day 15 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
Day 29 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
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Table 14.2.3.1.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Days 15, 29 and 57 
 (ITT Population) 
(Page 2 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Signs of AD Total Score 
Day 57 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 67 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.1.1 for the following: 
 
Table 14.2.3.1.2: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Days 15, 29 and 57 (mITT Population) 
 
Table 14.2.3.1.3: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Days 15, 29 and 57 (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 68 of 141 
CONFIDENTIAL 
Table 14.2.3.2.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit 
(ITT Population) 
(Page 1 of x) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Erythema 
Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
Day 15 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 69 of 141 
CONFIDENTIAL 
Table 14.2.3.2.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit 
(ITT Population) 
(Page 2 of x) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Erythema 
Day 29 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
Day 57 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
Programming note: Continue for Exudation, Excoriation, Induration/Papulation, Lichenification, and Total Score 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 70 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.2.1 for the following: 
 
Table 14.2.3.2.2: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit (mITT Population) 
 
Table 14.2.3.2.3: Exploratory Efficacy Endpoint: Summary of Signs of AD Score by Visit (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 71 of 141 
CONFIDENTIAL 
Table 14.2.3.3.1: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Days 15, 29 and 85 
 (ITT Population) 
(Page 1 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total BSA affected by 
AD 
Day 29 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
Day 57 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 72 of 141 
CONFIDENTIAL 
Table 14.2.3.3.1: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Days 15, 29 and 85 
 (ITT Population) 
(Page 2 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total BSA affected by 
AD 
Day 57 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 73 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.3.1 for the following: 
 
Table 14.2.3.3.2: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Days 15, 29 and 85 (mITT Population) 
 
Table 14.2.3.3.3: Exploratory Endpoint: Change from Baseline in Percent of Total BSA Affected by AD at Days 15, 29 and 85 (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 74 of 141 
CONFIDENTIAL 
Table 14.2.3.4.1: Summary of Percent of Total BSA Affected by AD by Visit 
(ITT Population) 
(Page 1 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Total BSA Affected by AD 
Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
Day 15 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 75 of 141 
CONFIDENTIAL 
Table 14.2.3.4.1: Summary of Percent of Total BSA Affected by AD by Visit 
(ITT Population) 
(Page 2 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Total BSA Affected by AD 
Day 29 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
Day 57 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 76 of 141 
CONFIDENTIAL 
Table 14.2.3.4.1: Summary of Percent of Total BSA Affected by AD by Visit 
(ITT Population) 
(Page 3 of 3) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Total BSA Affected by AD 
Day 85 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 77 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.4.1 for the following: 
 
Table 14.2.3.4.2: Summary of Percent of Total BSA Affected by AD by Visit (mITT Population) 
 
Table 14.2.3.4.3: Summary of Percent of Total BSA Affected by AD by Visit (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 78 of 141 
CONFIDENTIAL 
Table 14.2.3.5.1: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at Days 15, 29 and 57 
 (ITT Population) 
 
 
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID  
 
(N=xxx) 
 
 
Treatment  
 
 
P-Valuea 
 
At Least a 2 Grade Improvement from Baseline 
and IGA Grade of 0 or 1 
Day 15 
 n 
xx 
xx 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 Successa 
  xx.x% 
 
  xx.x% 
 
  
x.xxx 
 Failurea 
  xx.x% 
  xx.x% 
Day 29 
 n 
xx 
xx 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 Successa 
  xx.x% 
 
  xx.x% 
 
  
x.xxx 
 Failurea 
  xx.x% 
  xx.x% 
Day 57 
 n 
xx 
xx 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 Successa 
  xx.x% 
 
  xx.x% 
 
  
x.xxx 
 Failurea 
  xx.x% 
  xx.x% 
 
 
a Estimates and p-value from a logistic regression with a term for treatment group and adjusted for baseline IGA. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 79 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.5.1 for the following: 
 
Table 14.2.3.5.2: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at Days 15, 29 and 57 (mITT Population) 
 
Table 14.2.3.5.3: Exploratory Efficacy Endpoint: Summary of Dichotomized IGA Success at Days 15, 29 and 57 (PP Population) 
Programming note: Replace last footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 80 of 141 
CONFIDENTIAL 
Table 14.2.3.6.1: Summary of Investigator Global Assessment by Visit 
(ITT Population) 
(Page 1 of 4) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Baseline 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Day 15 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 81 of 141 
CONFIDENTIAL 
Table 14.2.3.6.1: Summary of Investigator Global Assessment by Visit 
(ITT Population) 
(Page 2 of 4) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Day 29 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 82 of 141 
CONFIDENTIAL 
Table 14.2.3.6.1: Summary of Investigator Global Assessment by Visit 
(ITT Population) 
(Page 3 of 4) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Day 57 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 83 of 141 
CONFIDENTIAL 
Table 14.2.3.6.1: Summary of Investigator Global Assessment by Visit 
(ITT Population) 
(Page 4 of 4) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Day 85 
n 
xx 
xx 
0 - Clear 
xx ( xx.x%) 
xx ( xx.x%) 
1 - Almost Clear 
xx ( xx.x%) 
xx ( xx.x%) 
2 - Mild 
xx ( xx.x%) 
xx ( xx.x%) 
3 - Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
4 - Severe 
xx ( xx.x%) 
xx ( xx.x%) 
IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
At Least a 2 Grade Improvement from Baseline and IGA Grade of 0 or 1 
 Success 
xx ( xx.x%) 
xx ( xx.x%) 
 Failure 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 84 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.6.1 for the following: 
 
Table 14.2.3.6.2: Summary of Investigator Global Assessment by Visit (mITT Population) 
 
Table 14.2.3.6.3: Summary of Investigator Global Assessment by Visit (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 85 of 141 
CONFIDENTIAL 
Table 14.2.3.7.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Target Lesions at Days 29, 57 and 85 
 (ITT Population) 
(Page 1 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total Signs of AD 
Day 29 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
Day 57 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 86 of 141 
CONFIDENTIAL 
Table 14.2.3.7.1: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Target Lesions at Days 29, 57 and 85 
 (ITT Population) 
(Page 2 of 2) 
  
 
BTX 1204 4% BID 
 
(N=xxx) 
 
 
Vehicle BID 
 
(N=xxx) 
 
 
Treatment 
 
P-Value 
 
Change from Baseline in Total Signs of AD 
Day 29 
 n 
xx 
xx 
 Mean 
xx.x 
xx.x 
 SD 
xx.xx 
xx.xx 
 Median 
xx.x 
xx.x 
 Min., Max. 
xx, xx 
xx, xx 
 LSMeana 
xx.x 
x.xxxa 
 LSSDa 
xx.xx 
 
a Least squares mean, standard deviation, and p-value from an analysis of covariance with baseline Total Signs of AD and treatment as covariates. 
Note: Missing values imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 87 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.7.1 for the following: 
 
Table 14.2.3.7.2: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Target Lesions at Days 29, 57 and 85 (mITT Population) 
 
Table 14.2.3.7.3: Exploratory Endpoint: Change from Baseline in Signs of AD Total Score at Target Lesions at Days 29, 57 and 85 (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 88 of 141 
CONFIDENTIAL 
Table 14.2.3.8.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target Lesions by Visit 
(ITT Population) 
(Page 1 of x) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Erythema 
Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
Day 15 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 89 of 141 
CONFIDENTIAL 
Table 14.2.3.8.1: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target Lesions by Visit 
(ITT Population) 
(Page 2 of x) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Erythema 
Day 29 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
Day 57 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
 Change from Baseline 
  n 
  
xx 
  
xx 
  Mean 
  
xx.x 
  
xx.x 
  SD 
  
xx.xx 
  
xx.xx 
  Median 
  
xx.x 
  
xx.x 
  Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
Note: Missing values are imputed using LOCF. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
Programming note: Continue for Exudation, Excoriation, Induration/Papulation, Lichenification, and Total Score 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 90 of 141 
CONFIDENTIAL 
Repeat Table 14.2.3.8.1 for the following: 
 
Table 14.2.3.8.2: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target Lesions by Visit (mITT Population) 
 
Table 14.2.3.8.3: Exploratory Efficacy Endpoint: Summary of Signs of AD Score at Target Lesions by Visit (PP Population) 
Programming note: Replace footnote with - Note: No imputations were made for missing data. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template           
 
Page 91 of 141 
CONFIDENTIAL 
Table 14.3.0.1: Summary of Extent of Exposure 
(Safety Population) 
(Page 1 of 2) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Total Amount of Study Drug Used (g) 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
Number of Applications 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
Number of  Missed Applications 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
a Compliant with the dosing regimen is if the subject applied at least 80% but no more than 120% of expected applications while enrolled in the study. 
b Percentages based on the number of subject in the safety population with percent compliance calculated. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.3.0.1: Summary of Extent of Exposure 
(Safety Population) 
(Page 2 of 2) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Percent Compliance 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
Complianta 
Yesb 
xx ( xx.x%) 
xx ( xx.x%) 
Nob 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a Compliant with the dosing regimen is if the subject applied at least 80% but no more than 120% of expected applications while enrolled in the study. 
b Percentages based on the number of subject in the safety population with percent compliance calculated. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.3.1.1: Summary of Treatment-Emergent Adverse Event Characteristics 
(Safety Population) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Number (%) of Subjects Reporting At Least One Treatment-Emergent 
Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Treatment-Emergent Adverse Events 
xx 
xx 
Number (%) of Subjects Reporting At Least Once Serious 
Treatment-Emergent Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Serious Treatment-Emergent Adverse Events 
xx 
xx 
Number (%) of Subjects who Discontinued Study Due to At Least One 
Treatment-Emergent Adverse Event 
xx ( xx.x%) 
xx ( xx.x%) 
Number of Treatment-Emergent Adverse Events Leading to 
Discontinuation of Study 
xx 
xx 
Maximum Severity 
Severe 
xx ( xx.x%) 
xx ( xx.x%) 
Moderate 
xx ( xx.x%) 
xx ( xx.x%) 
Mild 
xx ( xx.x%) 
xx ( xx.x%) 
Stongest Relationship to Study Drug 
Related 
xx ( xx.x%) 
xx ( xx.x%) 
Not Related 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
Note: Treatment-emergent adverse events are those with an onset on or after the date of first application of study drug. 
 
Percentages are based on the number of subjects in each treatment group in the Safety population. 
 
Related adverse events include possibly, probably, and definitely responses to relationship to study drug question. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.3.1.2: Summary of Treatment-Emergent Adverse Event by MedDRA System Organ Class and Preferred Term 
(Safety Population) 
System Organ Classa 
Preferred Term 
 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
System Organ Class 1 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 1 
xx ( xx.x%) 
xx ( xx.x%) 
Preferred Term 2 
xx ( xx.x%) 
xx ( xx.x%) 
… 
xx ( xx.x%) 
xx ( xx.x%
xx ( xx.x%) 
Preferred Term x 
xx ( xx.x%) 
xx ( xx.x%) 
… 
xx ( xx.x%) 
xx ( xx.x%) 
 
 
a At each level of summarization (System Organ Class or Preferred Term) subjecs are counted once. 
Note: MedDRA Version xx.x. 
 
Treatment-emergent adverse events are those with an onset on or after the date of first application of study drug. 
 
Percentages are based on the number of subjects in each treatment group in the Safety population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Repeat Table 14.3.1.2 for the following: 
 
Table 14.3.1.3: Summary of Serious Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term (Safety Population) 
 
Table 14.3.1.4: Summary of Related Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term (Safety Population) 
Programming note: Add footnote - Related adverse events include possibly, probably, and definitely responses to relationship to study drug question. 
 
Table 14.3.1.5: Summary of Severe Treatment-Emergent Adverse Events by MedDRA System Organ Class and Preferred Term (Safety Population) 
 
Table 14.3.1.6: Summary of Treatment-Emergent Adverse Events Leading to Study Discontinuation by MedDRA System Organ Class and Preferred Term 
(Safety Population) 
 
 
 


 
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Table 14.3.1.7: Summary of Time to Study Discontinuation for Subjects Who Discontinue Due to Treatment-Emergent Adverse Events 
(ITT Population) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Time to Study Discontinuationa 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
 
 
a Time to Study Discontinuation is calculated as study discontinuation date – date of first dose. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Repeat Table 14.3.1.2 for the following: 
 
Table 14.3.1.8: Summary of Treatment-Emergent Abuse-Related Adverse Events by MedDRA System Organ Class and Preferred Term (Safety Population) 
 
 


 
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Table 14.3.2.1.1: Summary of Chemistry Results by Visit 
(Safety Population) 
(Page 1 of y) 
Test Name (Units) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Baseline 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
Day 85 
n 
  
xx 
  
xx 
Mean 
  
xx.x 
  
xx.x 
SD 
  
xx.xx 
  
xx.xx 
Median 
  
xx.x 
  
xx.x 
Min., Max. 
  
xx, xx 
  
xx, xx 
Change from Baseline 
 n 
  
xx 
  
xx 
 Mean 
  
xx.x 
  
xx.x 
 SD 
  
xx.xx 
  
xx.xx 
 Median 
  
xx.x 
  
xx.x 
 Min., Max. 
  
xx, xx 
  
xx, xx 
[repeat for each test] 
 
 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Table 14.3.2.1.2: Shift Table for Chemistry Results 
(Safety Population) 
(Page 1 of y) 
 
Test Name (Units) 
 
Baseline 
 
BTX 1204 4% BID (N=xx) 
Day 85 (Na=xx) 
  
BNL 
  
WNL 
  
ANL 
 
BNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
WNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
ANL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
Vehicle BID (N=xx) 
Day 85 (Na=xx) 
BNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
WNL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
ANL 
xx ( xx.x%) 
xx ( xx.x%) 
xx ( xx.x%) 
[repeat for each test] 
 
 
a Number of subjects with both Baseline and Day 85 results for the given treatment group. 
Note: BNL=Below Normal Limit, WNL=Within Normal Limit, ANL=Above Normal Limit. 
 
Percentages are based on the number of subjects in the Safety population with both Baseline and Day 84 results. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Repeat Table 14.3.2.1.1 for the following: 
Table 14.3.2.2.1: Summary of CBC Results by Visit (Safety Population) 
Programming note: CBC tests include: WBC (with differentials for ANC, Neutrophils,Lymphocytes, monocytes, eosinophils, and basophils), RBC, Hemaglobin, 
Hematocrit, MCV, MCH, MCHC, and Platelet Count. Test names will be standardized to CDISC Controlled Terminology. 
 
Repeat Table 14.3.2.1.2 for the following: 
Table 14.3.2.2.2: Shift Table for CBC Results (Safety Population) 
 
Repeat Table 14.3.2.1.1 for the following: 
Table 14.3.2.3.1: Summary of Numeric Urinalysis Results by Visit (Safety Population) 
 
Repeat Table 14.3.2.1.2 for the following: 
Table 14.3.2.3.2: Shift Table for Numeric Urinalysis Results (Safety Population) 
 
 


 
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Table 14.3.2.3.3: Summary of Character Urinalysis Results by Visit 
(Safety Population) 
(Page 1 of y) 
Test Name (Units) 
  
BTX 1204 4% BID 
 
(N=xxx) 
 
  
Vehicle BID 
 
(N=xxx) 
 
Baseline 
n 
xx 
xx 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
Day 85 
n 
xx 
xx 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
xxxxxxx 
xx ( xx.x%) 
xx ( xx.x%) 
[repeat for each test] 
 
 
Note: Percentages are based on the number of subjects in the Safety population with a non-missing result for the given test and visit. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 


 
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11. INDEX OF PLANNED FIGURES 
Figure 14.2.1.5: Sensitivity Tipping-Point Analyses of the Primary Efficacy Endpoint: 
Dichotomized IGA Success at Day 85 (Intent-to-Treat Population) ..103 
Figure 14.2.2.4.4: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success (ITT 
Population) ..........................................................................................104 
Figure 14.2.2.4.5: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success (mITT 
Population) ..........................................................................................105 
Figure 14.2.2.4.6: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success (PP 
Population) ..........................................................................................105 


 
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Figure 14.2.1.5: Sensitivity Tipping-Point Analyses of the Primary Efficacy Endpoint: Dichotomized IGA Success at Day 85 
(Intent-to-Treat Population) 
  
  
 
 
 
 
Note: The horizontal and vertical axes indicate the potential number of successes among subjects with missing data in each treatment group. 
 
Each plotted point indicates the number of imputed successes in each treatment group that results in a p-value greater than 0.05. 
 
The red lines represent the number of imputed successes from the primary analysis using last observation carried forward (LOCF) to impute missing 
 
values. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 


 
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Figure 14.2.2.4.4: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success 
(ITT Population) 
 
 
 
 
Note: Circles represent censored observations. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE,TIME) 
 
 
 


 
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Repeat Table 14.2.2.4.4 for the following: 
 
Figure 14.2.2.4.5: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success (mITT Population) 
Figure 14.2.2.4.6: Secondary Endpoint: Kaplan Meier Curves for Time to IGA Success (PP Population) 
 


 
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12. INDEX OF PLANNED LISTINGS 
Listing 16.1.7: Randomization Scheme .......................................................................................108 
Listing 16.2.1.1: Subject Disposition Information.......................................................................109 
Listing 16.2.1.2: Discontinued Subjects ......................................................................................110 
Listing 16.2.1.3: Screen Failures .................................................................................................111 
Listing 16.2.2: Inclusion/Exclusion Criteria Not Met .................................................................112 
Listing 16.2.3: Analysis Populations ...........................................................................................113 
Listing 16.2.4.1: Subject Demographic Information ...................................................................114 
Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and 
Preferred Terms ...................................................................................115 
Listing 16.2.4.2.2: Medical History .............................................................................................116 
Listing 16.2.4.3.1: Unique Medication/Therapy Names Coded to WHO-DDE ATC Level 2 
Terms and Preferred Names ................................................................117 
Listing 16.2.4.3.2: Prior and Concomitant Medications/Therapies .............................................118 
Listing 16.2.4.3.3: Unique Antibiotic Therapy Names Coded to WHO-DDE ATC Level 2 Terms 
and Preferred Names ...........................................................................119 
Listing 16.2.4.3.4: Concomitant Antibiotic Therapies ................................................................120 
Listing 16.2.4.4: Physical Examination .......................................................................................121 
Listing 16.2.5.1: Study Drug Administration ..............................................................................122 
Listing 16.2.5.2: Drug Accountability .........................................................................................123 
Listing 16.2.5.3: Dosing Compliance ..........................................................................................124 
Listing 16.2.5.4: Dosing Deviations ............................................................................................125 
Listing 16.2.6.1: Investigator Global Assessment .......................................................................126 
Listing 16.2.6.2: Body Surface Area Affected by Atopic Dermatis ............................................127 
Listing 16.2.6.3: Investigator Assessed Signs of Atopic Dermatitis ...........................................128 
Listing 16.2.6.3: Signs of Atopic Dermatitis Based on Photography ..........................................129 
Listing 16.2.6.4: Itch Numeric Rating Score ...............................................................................130 
Listing 16.2.6.5: Photography Information..................................................................................131 
Listing 16.2.7.1.1: Unique Adverse Events Coded to MedDRA System Organ Classes and 
Preferred Terms ...................................................................................132 
Listing 16.2.7.1.2: Treatment-Emergent Adverse Events ............................................................133 
Listing 16.2.7.1.3: Serious Adverse Events .................................................................................134 


 
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Listing 16.2.7.1.4: Subjects Who Permanently Discontinued Study Drug and/or Discontinued 
from the Study Due to Adverse Events ...............................................135 
Listing 16.2.7.1.5: Unique Abuse-Related Adverse Events Coded to MedDRA System Organ 
Classes and Preferred Terms ...............................................................136 
Listing 16.2.7.1.6: Treatment-Emergent Abuse-Related Adverse Events ...................................137 
Listing 16.2.8.1: Urine Pregnancy Test Results ..........................................................................138 
Listing 16.2.8.2: Urine Drug Screen Results ...............................................................................139 
Listing 16.2.8.3.1.1: Complete Blood Count Laboratory Test Results........................................140 
Listing 16.2.8.3.1.2: Chemistry Laboratory Test Results ............................................................141 
Listing 16.2.8.3.1.3: Urinalysis Laboratory Test Results ............................................................141 


 
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Listing 16.1.7: Randomization Scheme 
                                                            (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                      Randomization       Randomization        Assigned                       Kit Dispensed  
Subject    Age/Sex     Evaluable      Number              Date                 Treatment Group                at Baseline 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx        xxxxxxxxx      xxxx                xxxx-xx-xx           xxxxxxx xxxxxx xxxx            xxxxx 
 
xxxxxx     xxxx        xxxxxxxxx      xxxx                xxxx-xx-xx           xxxxxxx                        xxxxx         
 
xxxxxx     xxxx        xxxxxxxxx      xxxx                xxxx-xx-xx           xxxxxxx xxxxxx  xxxx           xxxxx     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: ITT = Intent-to-Treat Population; mITT = modified Intent-To-Treat Population; S = Safety Population; PP = Per-Protocol 
Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject. 
 
 


 
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Listing 16.2.1.1: Subject Disposition Information 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                F: Date of                                E: Date (Day)¹ of                                
S: Subject         First Dose                                Completion/Discontinuation                       
A: Age/Sex      L: Date (Day)¹                            R: Reason for Study              
E: Evaluable       of Last Dose       Completion Status      Discontinuation              Additional Information² 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx       F: xxxx-xx-xx         xxxxx xxxxxxxxxxx   E: xxxx-xx-xx (xx)              Cause of Death: xxxxxxxxxxxxx 
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxx xxxxxxx xxxxxxx       Date of Death: xxxx-xx-xx 
E: xxxxxxxxx                                                                              Date of last contact: xxxx-xx-xx 
                                                                                          Lost to follow-up comment: xxxxxxx xxxxx 
                                                                                          Date the blind was broken: xxxx-xx-xx                     
                                                                                          Reason for breaking the blind: xxxxxx xxxxxx 
 
S: xxxxxx       F: xxxx-xx-xx         xxxxxxxxx           E: xxxx-xx-xx (xx)                           
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxxxxxx xx xxxxxxxxx                       
E: xxxxxxxxx                     
 
S: xxxxxx       F: xxxx-xx-xx         xxxxxxxxx           E: xxxx-xx-xx (xx)                           
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxxxxxx xx xxxxxxxxx                       
E: xxxxxxxxx                     
 
S: xxxxxx       F: xxxx-xx-xx         xxxxx xxxxxxxxxxx   E: xxxx-xx-xx (xx)              Cause of Death: xxxxxxxxxxxxx 
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxx xxxxxxx xxxxxxx       Date of Death: xxxx-xx-xx 
E: xxxxxxxxx                                                                              Date of last contact: xxxx-xx-xx  
                                                                                          Lost to follow-up comment: xxxxxxx xxxxx 
                                                                                          Date the blind was broken: xxxx-xx-xx                     
                                                                                          Reason for breaking the blind: xxxxxx xxxxxx 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
² Additional information is collected on a conditional basis. All information collected is included in the listing verbatim. 
Note: ITT = Intent-to-Treat Population; mITT = modified Intent-To-Treat Population; S = Safety Population; PP = Per-Protocol 
Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
Listing sorted by Subject.  
 
 


 
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Listing 16.2.1.2: Discontinued Subjects 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                F: Date of                                E: Date (Day)¹ of                                
S: Subject         First Dose                                Completion/Discontinuation                       
A: Age/Sex      L: Date (Day)¹                            R: Reason for Study              
E: Evaluable       of Last Dose       Completion Status      Discontinuation              Additional Information² 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx       F: xxxx-xx-xx         xxxxx xxxxxxxxxxx   E: xxxx-xx-xx (xx)              Cause of Death: xxxxxxxxxxxxx 
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxx xxxxxxx xxxxxxx       Date of Death: xxxx-xx-xx 
E: xxxxxxxxx                                                                              Date of last contact: xxxx-xx-xx 
                                                                                          Lost to follow-up comment: xxxxxxx xxxxx 
                                                                                          Date the blind was broken: xxxx-xx-xx                     
                                                                                          Reason for breaking the blind: xxxxxx xxxxxx 
 
S: xxxxxx       F: xxxx-xx-xx         xxxxxxxxx           E: xxxx-xx-xx (xx)                           
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxxxxxx xx xxxxxxxxx                       
E: xxxxxxxxx                     
 
S: xxxxxx       F: xxxx-xx-xx         xxxxxxxxx           E: xxxx-xx-xx (xx)                           
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxxxxxx xx xxxxxxxxx                       
E: xxxxxxxxx                     
 
S: xxxxxx       F: xxxx-xx-xx         xxxxx xxxxxxxxxxx   E: xxxx-xx-xx (xx)              Cause of Death: xxxxxxxxxxxxx 
A: xxxx         L: xxxx-xx-xx (xx)                        R: xxxxxx xxxxxxx xxxxxxx       Date of Death: xxxx-xx-xx 
E: xxxxxxxxx                                                                              Date of last contact: xxxx-xx-xx  
                                                                                          Lost to follow-up comment: xxxxxxx xxxxx 
                                                                                          Date the blind was broken: xxxx-xx-xx                     
                                                                                          Reason for breaking the blind: xxxxxx xxxxxx 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
² Additional information is collected on a conditional basis. All information collected is included in the listing verbatim. 
Note: ITT = Intent-to-Treat Population; mITT = modified Intent-To-Treat Population; S = Safety Population; PP = Per-Protocol 
Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
Listing sorted by Subject.  
 
 


 
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Listing 16.2.1.3: Screen Failures 
(Page x of xx) 
 
 _____________________________________________________________________________________________________________________________________ 
 
                            Date of                Reason for                  
 Subject        Age/Sex     Screen Failure         Screen Failure                          
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxxxxx      xxxx        xxxx-xx-xx             xxxxxxxxx xx xxxxxxx             
                                  
 xxxxxxxxx      xxxx        xxxx-xx-xx             xxxx xx xxxxxx xx                       
  
 xxxxxxxxx      xxxx        xxxx-xx-xx             xxxxxxx xxxxx                       
                                           
                                            
                                            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
_____________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
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Listing 16.2.2: Inclusion/Exclusion Criteria Not Met 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex     V: Study Visit      Inclusion/Exclusion 
E: Evaluable   D: Date             Criteria not met     Reason eligibility criteria not met 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      V: xxxxxxxxxxx      xxxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
A: xxxx        D: xxxx-xx-xx       xxxxxx               xxxxx xxxxxxxx xx xxxxxxxx xxxxxxx  
E: xxxxxxxxx                       xxxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxx  
 
S: xxxxxx      V: xxxxxxxxxxx      xxxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
A: xxxx        D: xxxx-xx-xx                            xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxxxxxxxxx 
E: xxxxxxxxx                         
 
S: xxxxxx      V: xxxxxxxxxxx      xxxxxx               xxxxx xxx xx xxxxxxxx xxxx xxxxxxxxxxxxxxxxxxx xxxxxxxx  
A: xxxx        D: xxxx-xx-xx                            xxxxxxxxxxxxxx xxxxxxxxx x xxxxxxxxxxxxxxxxx 
E: xxxxxxxxx                       xxxxxx               xxxx xxx xxxxxxxxxxxxx  xxxxxxx  xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: ITT = Intent-to-Treat Population; mITT = modified Intent-To-Treat Population; S = Safety Population; PP = Per-Protocol 
Population. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Criterion Failed. 
 
 


 
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Listing 16.2.3: Analysis Populations 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject    Age/Sex     Population                Included        Reason(s) Excluded                                   Exceptions 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx        Intent-to-Treat           xxx 
                       modifed Intent-to-Treat   xxx 
                       Safety                    xxx 
                       Per-Protocol              xx              xxxxxxxxxxx xxxxxxx xxxxxxxxx 
                                                                 xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
xxxxxx     xxxx        Intent-to-Treat           xxx 
                       modifed Intent-to-Treat   xxx 
                       Safety                    xxx 
                       Per-Protocol              xx              xxxxxxxxxxx xxxxxxx xxxxxxxxx 
                                                                 xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
xxxxxx     xxxx        Intent-to-Treat           xxx 
                       modifed Intent-to-Treat   xxx 
                       Safety                    xxx 
                       Per-Protocol              xxx             xxxxxxxxxxx xxxxxxx xxxxxxxxx                        xxxx xxxx xx 
                                                                 xxxxxxxxxxx xxxxxxx xxxxxxxxx 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject and Population (as ordered above). 
 
 


 
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Listing 16.2.4.1: Subject Demographic Information 
Treatment Group 
(Page xx of yy) 
 
 _____________________________________________________________________________________________________________________________________ 
                                                                                
                        B: Date of Birth                            
                        A: Age            R: Race                  Date of                                 Childbearing    Photography    
 Subject  Evaluable     S: Sex            E: Ethnicity             Informed Consent      Date of Assesnt     Potential       Consent      
 _____________________________________________________________________________________________________________________________________ 
 
 xxxxxx   xxxxxxxxx     B: xxxx-xx-xx     R: xxxxxx xxxxxxxx       xxxx-xx-xx            xxxx-xx-xx            xx             xxx         
                        A: xx                xx xxxxx xxxxxxx      
                        S: xxxxxx            xxxxxxxx xxxxxxxxxx       
                                          E: xxx xxxxxxxx xx           
                                             xxxxxx                    
                                                                      
 
 xxxxxx   xxxxxxxxx     B: xxxx-xx-xx     R: xxxxx                 xxxx-xx-xx            xxxx-xx-xx            xx             xxx         
                        A: xx             E: xxxxxxxx xx xxxxxx     
                        S: xxxx            
 
 xxxxxx   xxxxxxxxx     B: xxxx-xx-xx     R: xxxxx                 xxxx-xx-xx            xxxx-xx-xx            xx             xxx         
                        A: xx             E: xxxxxxxx xx xxxxxx     
                        S: xxxxxx            
 
 
 
 
 
 
 
 
 
 
 
 
 _____________________________________________________________________________________________________________________________________ 
 Note: ITT = Intent-to-Treat Population; mITT = modified Intent-to-Treat Population; S = Safety Population; PP = Per-Protocol    
 Population. 
 SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 Listing sorted by Subject. 
Note to Programmer: Race will be displayed as the mapped CDISC version of the verbatim text. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 115 of 141  
CONFIDENTIAL 
Listing 16.2.4.2.1: Unique Medical History Coded to MedDRA System Organ Classes and Preferred Terms 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class                     MedDRA Preferred Term                       Condition/Surgery Verbatim Term 
______________________________________________________________________________________________________________________________________ 
 
xxxx xxx xxxxx                                xxxx xxx xxxxx                              xxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxx 
 
 
xxxx xxx xxxxx                                xxxx xxx xxxxx                              xxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxxx 
 
                                                                                          xxxxxx xxxxxxxxxx xx xxxxx 
 
 
 
 
 
 
 
 
 
 
 
                                                                                           
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to the MedDRA dictionary (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
Listing sorted by System Organ Class, Preferred Term, and Medical History. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 116 of 141  
CONFIDENTIAL 
Listing 16.2.4.2.2: Medical History 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
        
                                                                                                       
 
                                    Condition/Surgery            
  P: MedDRA Preferred Term              S: Start Date (Day)¹ 
Subject    Age/Sex    Evaluable     Verbatim Term                  
  S: MedDRA System Organ Class          E: End Date (Day)¹            
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       xxxxxxxx      xxxxxx xxxxxxx xxxxxxxxxxxx  
  P: xxxxxx xxxxxxxxxx                  S: xxxx-xx-xx (xx) 
                                                                    
  S: xxxxxxxxxxx xxxxxxx                E: xxxxxxx  
 
 
 
 
  
                                    xxxxxxxx xxxxxxxxxx                P: xxxxxxx xxxxxxxx                   S: xxxx-xx-xx (xx) 
                                                                    
  S: xxxxxxxx xxx xxxxxxxx              E: xxxx-xx-xx (xx) 
 
 
 
 
 
 
 
  
 
 
                    
           
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: System Organ Class and Preferred Term map to MedDRA (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Medical Condition/Surgery, Start Date, and End Date. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 117 of 141  
CONFIDENTIAL 
Listing 16.2.4.3.1: Unique Medication/Therapy Names Coded to WHO-DDE ATC Level 2 Terms and Preferred Names 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                             I: Indication 
ATC Level 2 Term                 Preferred Name                    Medication/Therapy Name                   R: Route 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx xxxxxx xx xxx             xxxxxxxxxx                        xxxxxxxxxx                                I: xxxxxxx xxxxxxxx 
                                                                                                             R: xxxx 
 
                                 xxxxxxx x                         xxxxxx                                    I: xxxxxxx xxxxxxxx 
                                                                                                                xxxxxxxxxxxx 
                                                                                                             R: xxxx 
 
                                 xxxxxxxxx                         xxxxxxxxx                                 I: xxxxxxx xxxxxxxx xxxx 
                                                                                                                xxxxx xxxxxxxx 
                                                                                                             R: xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: Preferred Name and ATC Level 2 Term map to the WHO-DDE, Format B2, Version xxxxx. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
Listing sorted by ATC Level 2 Term, Standardized Medication Name, Medication Name, Indication, and Route. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 118 of 141  
CONFIDENTIAL 
Listing 16.2.4.3.2: Prior and Concomitant Medications/Therapies 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                      M: Medication/Therapy Name                                                D: Dose 
                                      P: Preferred Name                       T: Prior/Concomitant              U: Units 
                                      A: ATC Level 2 Term                     S: Start Date/Time (Day)¹         F: Frequency 
Subject     Age/Sex    Evaluable      I: Indication                           E: End Date/Time (Day)¹           R: Route  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxx-xx-xxTxx:xx:xx (xx)       F: xxxx 
                                      I: xxxxxxxx                                                               R: xxxxxx  
                                                                                                               
                                      M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xxxxx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxx-xx-xxTxx:xx:xx (xx)       F: xx 
                                      I: xxxxxxxx                                                               R: xxxx 
                                                                                                               
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xxx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxxxxx                        F: xx 
                                      I: xxxxxxxx                                                               R: xxxx 
                                                                                                        
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: Preferred Name and ATC Level 2 Term map to the WHO-DDE, Format B2, Version xxxxx. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, and Route.  If ongoing, include ‘Ongoing’ in place of 
End Date. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 119 of 141  
CONFIDENTIAL 
Listing 16.2.4.3.3: Unique Antibiotic Therapy Names Coded to WHO-DDE ATC Level 2 Terms and Preferred Names 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                                             I: Indication 
ATC Level 2 Term                 Preferred Name                    Medication/Therapy Name                   R: Route 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx xxxxxx xx xxx             xxxxxxxxxx                        xxxxxxxxxx                                I: xxxxxxx xxxxxxxx 
                                                                                                             R: xxxx 
 
                                 xxxxxxx x                         xxxxxx                                    I: xxxxxxx xxxxxxxx 
                                                                                                                xxxxxxxxxxxx 
                                                                                                             R: xxxx 
 
                                 xxxxxxxxx                         xxxxxxxxx                                 I: xxxxxxx xxxxxxxx xxxx 
                                                                                                                xxxxx xxxxxxxx 
                                                                                                             R: xxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: Preferred Name and ATC Level 2 Term map to the WHO-DDE, Format B2, Version xxxxx. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
Listing sorted by ATC Level 2 Term, Standardized Medication Name, Medication Name, Indication, and Route. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 120 of 141  
CONFIDENTIAL 
Listing 16.2.4.3.4: Concomitant Antibiotic Therapies 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                      M: Medication/Therapy Name                                                D: Dose 
                                      P: Preferred Name                       T: Prior/Concomitant              U: Units 
                                      A: ATC Level 2 Term                     S: Start Date/Time (Day)¹         F: Frequency 
Subject     Age/Sex    Evaluable      I: Indication                           E: End Date/Time (Day)¹           R: Route  
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxx-xx-xxTxx:xx:xx (xx)       F: xxxx 
                                      I: xxxxxxxx                                                               R: xxxxxx  
                                                                                                               
                                      M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xxxxx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxx-xx-xxTxx:xx:xx (xx)       F: xx 
                                      I: xxxxxxxx                                                               R: xxxx 
                                                                                                               
 
xxxxxx      xxxx       xxxxxxxxxx     M: xxxxxxxxxxxxx                        T: xxxxxxxxxx                     D: xxx 
                                      P: xxxxxxxxxxxxx                        S: xxxx-xx-xxTxx:xx:xx (xx)       U: xx 
                                      A: xxxxxxxxxxxxx                        E: xxxxxxx                        F: xx 
                                      I: xxxxxxxx                                                               R: xxxx 
                                                                                                        
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: Preferred Name and ATC Level 2 Term map to the WHO-DDE, Format B2, Version xxxxx. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
Listing sorted by Subject, Start Date, End Date, Medication Name, Indication, and Route.  If ongoing, include ‘Ongoing’ in place of 
End Date. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 121 of 141  
CONFIDENTIAL 
Listing 16.2.4.4: Physical Examination 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________                
                 
                               
S: Subject          
                 
                                
A: Age/Sex      V: Visit          H: Height (cm)             
                          Abnormal                         
E: Evaluable    D: Date of Exam   W: Weight (kg)   Body System Assessed      Result          Description            Reason Not Done 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx       V: xxxxxxxxxxx    H: xxx           General Appearance        xxxxxxxxx                    
A: xxxx         D: xxxx-xx-xx     W: xx            Cardiovascular            xxxxxxxxx            
E: xxxxxxxxx                                       Neurological              xxxxxxxxxxx      xxxxxx xxxxxxxxx           
                                                   Musculoskeletal           xxxxxxxxx 
                                                   Extremities/Skin          xxxxxxxxx    
                                    
S: xxxxxx       V: xxxxxxxxxxx    H: xxx           General Appearance        xxxxxxxxx                    
A: xxxx         D: xxxx-xx-xx     W: xx            Cardiovascular            xxxxxxxxx            
E: xxxxxxxxx                                       Neurological              xxxxxxxxx       
                                                   Musculoskeletal           xxx xxxx                               xxxxxxx xxxxx xxxx 
                                                   Extremities/Skin          xxxxxxxxxxx      xxxxxxxxxxxx                                             
 
S: xxxxxx       V: xxxxxxxxxxx    H:                                         xxx xxxx                               xxx xxx xxxx xx 
A: xxxx         D:                W:                 
E: xxxxxxxxx                                        
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date, Body System Assessed. 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 122 of 141  
CONFIDENTIAL 
Listing 16.2.5.1: Study Drug Administration 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________                 
                                     
                                                                         Where was the 
                                                Date/Time                Study Drug 
Subject   Age/Sex   Evaluable    Visit          of Administration        Administered?      Reason Not Administered 
______________________________________________________________________________________________________________________________________ 
 
xxxxxxx   xxxx      xxxxxxxxx    xxxxxxxxx      xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
 
xxxxxxx   xxxx      xxxxxxxxx    xxxxxxxxx      xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxx 
                                 xxx xx                                  xxx xxxxxxxxxx     xx xxxxx xxxxxxxxxx 
 
xxxxxxx   xxxx      xxxxxxxxx    xxxxxxxxx      xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
                                 xxx xx         xxxx-xx-xxTxx:xx:xx      xxxxxx 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, visit, Date/Time. 
 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 123 of 141  
CONFIDENTIAL 
Listing 16.2.5.2: Drug Accountability 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                              Date           Date                         Dispensed      Where was        Returned 
Subject  Age/Sex  Evaluable    Kit Number     Dispensed      Returned      Pump ID        Weight (g)     IP Applied       Weight (g) 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx   xxxx     xxxxxxxx     xxxxx          xxxx-xx-xx     xxxx-xx-xx      x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxx  xxxxxx    xx.x 
                                                                             x            xx.x           xxxxx  xxxxxx    xx.x 
                                                                             x            xx.x           xxxxx  xxxxxx    xx.x 
 
                               xxxxx          xxxx-xx-xx     xxxx-xx-xx      x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
 
                               xxxxx          xxxx-xx-xx     xxxx-xx-xx      x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
 
xxxxxx   xxxx     xxxxxxxx     xxxxx          xxxx-xx-xx     xxx xxxx        x            xx.x               
                                                                             x            xx.x                                
                                                                             x            xx.x                              
                                                                             x            xx.x                              
 
                               xxxxx          xxxx-xx-xx     xxxx-xx-xx      x            xx.x               
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
                                                                             x            xx.x           xxxxxx xxxxxx    xx.x 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Kit Number, Date Dispensed, Date Returned.  
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 124 of 141  
CONFIDENTIAL 
Listing 16.2.5.3: Dosing Compliance 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject                             Calculated¹  Amount of                                                            
A: Age/Sex     D: Date of First Dose    Number of   Study Drug      Number of          Percent                    
E: Evaluable   R: Date of Last Dose      Doses       Used (g)      Missed Doses        Complaint     Compliant?²     
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      D: xxxx-xx-xx              xx           xxxx             x              xxx           xxx            
A: xxxx        R: xxxx-xx-xx  
E: xxxxxxxxx                     
 
S: xxxxxx      D: xxxx-xx-xx              xx           xxxx             x              xxx           xx               
A: xxxx        R: xxxx-xx-xx   
E: xxxxxxxxx                     
 
S: xxxxxx      D: xxxx-xx-xx              xx           xxxx                            xxxx          xxx            
A: xxxx        R: xxxx-xx-xx   
E: xxxxxxxxx                     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ The total number of doses was calculated from the date of first dose and the date of last known dose minus the missed doses. 
² A subject was considered compliant with the dosing regimen if the subject applied at least 80% but no more than 120% of the   
  expected applications. 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 125 of 141  
CONFIDENTIAL 
Listing 16.2.5.4: Dosing Deviations 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                        Date (Day)¹ of       Morning or             
Subject     Age/Sex     Evaluable       Missed Dose        Afternoon dose?     Reason for Missed Dose 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx        xxxx      xxxxxxxx        xxxx-xx-xx (xx)          xx            xxxxx xxxxxxxxx xxxxxxxx 
                                        xxxx-xx-xx (xx)          xx            xxxxxxxx 
                                        xxxx-xx-xx (xx)          xx            xxxxxxx xx 
 
xxxxxx        xxxx      xxxxxxxx        xxxx-xx-xx (xx)          xx            xxxxxxxxx xxxxxxxxxxx  xx xxxxx x xxxxxxx 
                                        xxxx-xx-xx (xx)          xx            xxxxxxxxx xxxxxxxxxxx  xx xxxxx x xxxxxxx 
                                        xxxx-xx-xx (xx)          xx            xxxxxxxxx xxxxxxxxxxx  xx xxxxx x xxxxxxx 
 
xxxxxx        xxxx      xxxxxxxx        xxxx-xx-xx (xx)          xx            xxxxxxx xx 
                                        xxxx-xx-xx (xx)          xx            xxx xxx 
                                                   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 126 of 141  
CONFIDENTIAL 
Listing 16.2.6.1: Investigator Global Assessment 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                                             Two Grade  
                                                                                             Reduction from  
S: Subject                                                                 Two Grade         Baseline and 
A: Age/Sex                                                                 Reduction from    Achieving Clear     Evaluator Initials 
E: Evaluable       Visit           Date/Time           Result              Baseline          or Almost Clear     or Reason Not Done 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx          xxxxxxxx        xxxx-xx-xxTxx:xx    x – xxxx                                                  xxx 
A: xxxx 
E: xxxxxxxx 
                   xxxxxxxx        xxxx-xx-xxTxx:xx    x – xxxxxx                                                xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x - xxxxxxxx        xx                xx                  xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x – xxxx            xx                xx                  xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x – xxxx            xx                xx                  xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x – xxxxxx xxxxx    xx                xx                  xxx 
 
S: xxxxxx          xxxxxxxx        xxxx-xx-xxTxx:xx    x - xxxxxxxx                                              xxx 
A: xxxx 
E: xxxxxxxx 
                   xxxxxxxx        xxxx-xx-xxTxx:xx    x - xxxxxxxx                                              xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x - xxxxxxxx        xx                xx                  xxx 
                   xxxxxx          xxxx-xx-xxTxx:xx    x – xxxx            xx                xx                  xxx 
                   xxxxxx                              xxx xxxx                                                  xxx xxxxxx xxx xx 
                                                                                                                 xxxxxxxxxx  
                   xxxxxx          xxxx-xx-xxTxx:xx    x – xxxx            xx                xx                  xxx 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 127 of 141  
CONFIDENTIAL 
Listing 16.2.6.2: Body Surface Area Affected by Atopic Dermatis 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex                                       Evaluator                                         Change from                     
E: Evaluable       Visit           Date          Initials     Location                  Result     Bsaeline      Reason Not Done   
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx          xxxxxxxxx       xxxx-xx-xx    xxx          Head and Neck             x.x% 
A: xxxx 
E: xxxxxxxx 
                                                              Right Arm                 x.x% 
                                                              Left Arm                  x.x% 
                                                              Right Leg                 x.x% 
                                                              Left Leg                  x.x% 
                                                              Trunk Front               x.x% 
                                                              Trunk Back                x.x% 
                                                              Total Body Surface Area   x.x% 
 
                   xxxxxxxx        xxxx-xx-xx    xxx          Head and Neck             x.x% 
                                                              Right Arm                 x.x% 
                                                              Left Arm                  x.x% 
                                                              Right Leg                 x.x% 
                                                              Left Leg                  x.x% 
                                                              Trunk Front               x.x% 
                                                              Trunk Back                x.x% 
                                                              Total Body Surface Area   x.x% 
 
                   xxxxxx          xxxx-xx-xx    xxx          Head and Neck             x.x% 
                                                              Right Arm                 x.x% 
                                                              Left Arm                  x.x% 
                                                              Right Leg                 x.x% 
                                                              Left Leg                  x.x% 
                                                              Trunk Front               x.x% 
                                                              Trunk Back                x.x% 
                                                              Total Body Surface Area   x.x%      x.x 
 
                   xxxxx          xxxx-xx-xx    xxx           Head and Neck             x.x% 
                                                              Right Arm                 x.x% 
                                                              Left Arm                  x.x% 
                                                              Right Leg                 x.x% 
                                                              Left Leg                  x.x% 
                                                              Trunk Front               x.x% 
                                                              Trunk Back                x.x% 
                                                              Total Body Surface Area   x.x%      x.x 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 128 of 141  
CONFIDENTIAL 
Listing 16.2.6.3: Investigator Assessed Signs of Atopic Dermatitis 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex                                   Evaluator    Signs of                                 Change from                     
E: Evaluable   Visit           Date          Initials     Atopic Dermatitis        Result          Baseline      Reason Not Done   
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      xxxxxxxxx       xxxx-xx-xx    xxx          Erythema                 x – xxxx 
A: xxxx 
E: xxxxxxxx 
                                                          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x  
 
               xxxxxxxx        xxxx-xx-xx    xxx          Erythema                 x  
                                                          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x  
 
               xxxxxx          xxxx-xx-xx                 All Signs of AD          xxx xxxx                      xxxxxx xxxx xxx 
 
               xxxxxx          xxxx-xx-xx    xxx          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x                x 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 129 of 141  
CONFIDENTIAL 
Listing 16.2.6.3: Signs of Atopic Dermatitis Based on Photography 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
S: Subject 
A: Age/Sex                                   Evaluator    Signs of                                 Change from                     
E: Evaluable   Visit           Date          Initials     Atopic Dermatitis        Result          Baseline      Reason Not Done   
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      xxxxxxxxx       xxxx-xx-xx    xxx          Erythema                 x – xxxx 
A: xxxx 
E: xxxxxxxx 
                                                          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x  
 
               xxxxxxxx        xxxx-xx-xx    xxx          Erythema                 x  
                                                          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x  
 
               xxxxxx          xxxx-xx-xx                 All Signs of AD          xxx xxxx                      xxxxxx xxxx xxx 
 
               xxxxxx          xxxx-xx-xx    xxx          Exudation                x  
                                                          Excoriation              x  
                                                          Induration/papulation    x  
                                                          Lichenification          x  
                                                          Total Score              x                x 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 130 of 141  
CONFIDENTIAL 
Listing 16.2.6.4: Itch Numeric Rating Score 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                                  How Would You Rate 
                                                                  Your Average Itch             Change   
Subject    Age/Sex    Evaluable    Visit           Date           in the Past 24 Hours          from Baseline          Reason Not Done 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx     xxxx       xxxxxxxx     xxxxxxxxx       xxxx-xx-xx     x 
                                   xxxxxxxx        xxxx-xx-xx     x                                                 
                                   xxxxxx          xxxx-xx-xx     x                            xx                              
                                   xxxxxx          xxxx-xx-xx     x                            xx                               
                                   xxxxxx          xxxx-xx-xx     x                            xx                               
                                   xxxxxx          xxxx-xx-xx     x                            xx                               
 
S: xxxxxx  xxxx       xxxxxxxx     xxxxxxxxx       xxxx-xx-xx     x                                        
                                   xxxxxxxx        xxxx-xx-xx     x                                        
                                   xxxxxx          xxxx-xx-xx     x                            xx                               
                                   xxxxxx          xxxx-xx-xx     x                            xx                                
                                   xxxxxx                         xxx xxxx                                              xxx xxxxxxxxxx 
                                                                                                                        xxxxxxxxxx  
                                   xxxxxx          xxxx-xx-xx     x                            xx                                  
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 131 of 141  
CONFIDENTIAL 
Listing 16.2.6.5: Photography Information 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
                                                            Were Photographs of the    Reason Photographs         Date of 
Subject   Age/Sex   Evaluable       Visit                   Target Lesions Obtained?   Not Obtained               Photograph 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx    xxxx      xxxxx           xxxxxxxx                xxx                                                   xxxx-xx-xx  
                                    xxxx xxxxxxxxx          xxx                                                   xxxx-xx-xx  
 
xxxxxx    xxxx      xxxxxxxx        xxxxxxxx                xxx                                                   xxxx-xx-xx  
                                    xxxx xxxxxxxxx          xx                         xxxxx xxxxxx xxx                                
   
xxxxxx    xxxx      xxxxxxxx        xxxxxxxx                xxx                                                   xxxx-xx-xx  
                                    xxxx xxxxxxxxx          xxx                                                   xxxx-xx-xx  
 
xxxxxx    xxxx      xxxxx           xxxxxxxx                xxx                                                   xxxx-xx-xx  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 


 
TOOL.AN.10-01.01 Statistical Analysis Plan Template 
 
Page 132 of 141  
CONFIDENTIAL 
Listing 16.2.7.1.1: Unique Adverse Events Coded to MedDRA System Organ Classes and Preferred Terms 
 (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class                      MedDRA Preferred Term                       Adverse Event 
______________________________________________________________________________________________________________________________________ 
 
xxxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx           xxxxxxx                                     xxxxxx 
 
                                                                                           xxxxxx 
 
                                               xxxxxxxxxxxx                                xxxxxxxxxxxx 
 
xxx xxx xxxxxxxxx xxxxxxxxx                    xxxxxxx                                     xxxxxxx 
 
xxx xxxxxxxxx                                  xxxxxx xxxxxx xxxxxxx                       xxxxxxxxx xxxxxx xxxxxx 
 
xxxxxxxxxxxxxxxx xxxxxxxxx                     xxxxxxxxx xxxx                              xxxxxxxxx xxxx 
 
                                               xxxxxxxxx xxxxxxxxxxxx                      xxxxx xxxxxxxxx xxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to the MedDRA dictionary (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by MedDRA System Organ Class, Preferred Term, and Adverse Event. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.7.1.2: Treatment-Emergent Adverse Events 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                     
                                                    S: Start Date (Day)¹        S: Severity                 S: Is AE Serious?          
S: Subject     A: Adverse Event                     E: End Date (Day)1           R: Relationship to          R: Reason(s) for Serious   
A: Age/Sex     C: System Organ Class                A: Action Take with             Study Drug              T: Medical Treatment 
E: Evaluable   P: Preferred Term                       Study Treatment          O: Outcome                     Received? 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R:   
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxx xxxxxxxx  
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxxxxx xxxxxxxxx 
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
 
 
 
 
 
 
  
______________________________________________________________________________________________________________________________________ 
¹ ¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: System Organ Class and Preferred Term map to MedDRA (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
Programming Notes: If an adverse event is indicated as serious the reason(s) for the event being serious will be listed under the  
R: Reason(s) for Serious column and serperated by a comma. Possible reason(s) include: Fatal, Life-threatening event, Hospitalization 
or prolongation of hospitalization, Persistent or significant disability/incapacity, Congenital Anomaly or Birth Defect, Important 
Medical Event. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.7.1.3: Serious Adverse Events 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                                                                     
                                                    S: Start Date (Day)¹        S: Severity                 S: Is AE Serious?          
S: Subject     A: Adverse Event                     E: End Date (Day)1           R: Relationship to          R: Reason(s) for Serious   
A: Age/Sex     C: System Organ Class                A: Action Take with             Study Drug              T: Medical Treatment 
E: Evaluable   P: Preferred Term                       Study Treatment          O: Outcome                     Received? 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R:   
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxx xxxxxxxx  
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxxxxx xxxxxxxxx 
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xxxx xxx xxxxxxx         O: xxxxxxxxxx               T: xxx 
 
 
 
 
 
 
 
  
______________________________________________________________________________________________________________________________________ 
¹ ¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: System Organ Class and Preferred Term map to MedDRA (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.7.1.4: Subjects Who Permanently Discontinued Study Drug and/or Discontinued from the Study Due to Adverse Events 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
                                                   
                                                    S: Start Date (Day)¹         
                                                    E: End Date (Day)1                 S: Severity            S: Is AE Serious?          
S: Subject     A: Adverse Event                     T: Time to Discontinuation (days) R: Relationship to     R: Reason(s) for Serious   
A: Age/Sex     C: System Organ Class                A: Action Take with                  Study Drug          T: Medical Treatment 
E: Evaluable   P: Preferred Term                       Study Treatment                O: Outcome                Received? 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)                G: xxxx                S: xx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)                R: xxxxxxxxxx          R:   
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   T: xx                             O: xxxxxxxxxx          T: xxx 
                                                    A: xxxx xxx xxxxxxx          
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)                G: xxxx                S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)                R: xxxxxxxxxx          R: xxxxxx xxxxxxxx  
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   A: xx                             O: xxxxxxxxxx          T: xxx 
                                                    A: xxxx xxx xxxxxxx          
 
S: xxxxxx      A: xxxxxxxxxxxxxxx                   S: xxxx-xx-xx (xx)                G: xxxx                S: xxx 
A: xxx xx      C: xxxxxxxxxxxxxxx                   E: xxxx-xx-xx (xx)                R: xxxxxxxxxx          R: xxxxxxxxx  
E: xxxxxxxxx   P: xxxxxxxxxxxxxxx                   T: xx                             O: xxxxxxxxxx          T: xxx 
                                                    A: xxxx xxx xxxxxxx          
 
 
 
 
 
 
 
  
______________________________________________________________________________________________________________________________________ 
¹ ¹ Day = (date – date of first dose + 1) for dates on or after first dose. Otherwise, Day = (date – date of first dose). 
Note: System Organ Class and Preferred Term map to MedDRA (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Start Date, End Date, and Adverse Event. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.7.1.5: Unique Abuse-Related Adverse Events Coded to MedDRA System Organ Classes and Preferred Terms 
 (Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
MedDRA System Organ Class                      MedDRA Preferred Term                       Adverse Event 
______________________________________________________________________________________________________________________________________ 
 
xxxxx xxx xxxxxxxxx xxxxxx xxxxxxxxx           xxxxxxx                                     xxxxxx 
 
                                                                                           xxxxxx 
 
                                               xxxxxxxxxxxx                                xxxxxxxxxxxx 
 
xxx xxx xxxxxxxxx xxxxxxxxx                    xxxxxxx                                     xxxxxxx 
 
xxx xxxxxxxxx                                  xxxxxx xxxxxx xxxxxxx                       xxxxxxxxx xxxxxx xxxxxx 
 
xxxxxxxxxxxxxxxx xxxxxxxxx                     xxxxxxxxx xxxx                              xxxxxxxxx xxxx 
 
                                               xxxxxxxxx xxxxxxxxxxxx                      xxxxx xxxxxxxxx xxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
Note: System Organ Class and Preferred Term map to the MedDRA dictionary (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by MedDRA System Organ Class, Preferred Term, and Adverse Event. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.7.1.6: Treatment-Emergent Abuse-Related Adverse Events 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________                 
                                                                                                     
                                                                        S: Severity                            
S: Subject       A: Adverse Event                                       R: Relationship to          S: Is AE Serious?                  
A: Age/Sex       C: System Organ Class      S: Start Date (Day)¹           Study Drug               R: Reason(s) for Serious  
E: Evaluable     P: Preferred Term          E: End Date (Day)1           O: Outcome                  T: Medical Treatment Received? 
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)          G: xxxx                     S: xx 
A: xxx xx        C: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R:   
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx                                     O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx        C: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxx xxxxxxxx  
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx                                     O: xxxxxxxxxx               T: xxx 
 
S: xxxxxx        A: xxxxxxxxxxxxxxx         S: xxxx-xx-xx (xx)          G: xxxx                     S: xxx 
A: xxx xx        C: xxxxxxxxxxxxxxx         E: xxxx-xx-xx (xx)          R: xxxxxxxxxx               R: xxxxxxxxx xxxxxxxxx 
E: xxxxxxxxx     P: xxxxxxxxxxxxxxx                                     O: xxxxxxxxxx               T: xxx 
 
 
 
 
 
 
 
  
______________________________________________________________________________________________________________________________________ 
¹ Day is calculated as date – date of first dose for dates prior to first dose.  Otherwise, day is calculated as 
  date – date of first dose + 1 for dates on or after first dose. 
Note: System Organ Class and Preferred Term map to MedDRA (Version xx.x). 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
 
 


 
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CONFIDENTIAL 
Listing 16.2.8.1: Urine Pregnancy Test Results 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject   Age/Sex   Evaluable        Visit                Date/Time                       Results 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx    xxxxxxxx         xxxxxxxxx            xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxxxxxxx             xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
 
xxxxxx      xxxx    xxxxxxxx         xxxxxxxxx            xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxxxxxxx             xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxxx xxxxxxxxx       xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
 
xxxxxx      xxxx    xxxxxxxx         xxxxxxxxx            xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxxxxxxx             xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxx xx               xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
                                     xxxx xxxxxxxxx       xxxx-xx-xxTxx:xx:xx             xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.8.2: Urine Drug Screen Results 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
 
Subject   Age/Sex   Evaluable    Visit           Date/Time               Results          Positive Drugs       Reason Not Done 
______________________________________________________________________________________________________________________________________ 
 
xxxxxx      xxxx    xxxxxxxx     xxxxxxxxx       xxxx-xx-xxTxx:xx:xx     xxxxxxxx         xxxxxxxxxxx 
                                 xxxxxxxxx       xxxx-xx-xxTxx:xx:xx     xxxxxxxx 
 
xxxxxx      xxxx    xxxxxxxx     xxxxxxxxx       xxxx-xx-xxTxx:xx:xx     xxxxxxxx 
                                 xxxxxxxxx                                                                     xxxxx xxxxxxx 
                                      
 
xxxxxx      xxxx    xxxxxxxx     xxxxxxxxx       xxxx-xx-xxTxx:xx:xx     xxxxxxxx 
                                 xxxxxxxxx       xxxx-xx-xxTxx:xx:xx     xxxxxxxx         xxxxxxxxx xxxxxxx 
                                                                                          xxxxxxxxxxxxxx 
                                      
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
______________________________________________________________________________________________________________________________________ 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Programming Notes: The Positive Drugs column will list all of the drugs that apply as positive or (Yes) for the drug screen, each 
separated by a comma. For example if the Result is Positive and the drug screen found Amphetamines and Methamphetamines as Positive 
then they will be listed as Amphetamines, Methamphetamines. 
Listing sorted by Subject, Visit, Date. 
 
 


 
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CONFIDENTIAL 
Listing 16.2.8.3.1.1: Complete Blood Count Laboratory Test Results 
Treatment Group 
(Page xx of yy) 
 
______________________________________________________________________________________________________________________________________ 
    
S: Subject     
A: Age/Sex    V: Visit                                       Results       _________Reference Range__________      Reason Not Done/   
E: Evaluable  D: Date/Time             Laboratory Test       (Units)        Low      High      Indicator(CS¹)      Comments      
______________________________________________________________________________________________________________________________________ 
 
S: xxxxxx     V: xxxxxxxxx             xxxxxxxxxxxxxxxxxx    xxx xxx        x        xx        xxxxxx xxxx    
A: xxxx       D: xxxx-xx-xxTxx:xx:xx    
E: xxxxxxxxx                            
                                       xxxxxxxxxxx           xxx xxxxxx     xx       xx        xxxxxx xxxx    
                                       xxxxxxxxxxxxxxxx      xxx xxxxxx     xx       xx        xxxxxx xxxx    
                                       xxxxxxxxxxxxxxxxxx    xxx xxxxxx     xx       xx        xxxxxx xxxx    
 
              V: xxxxxxxxx             xxxxxxxx              xxx xxxxxx     xx       xx        xxxxxx xxxx            
              D: xxxx-xx-xxTxx:xx:xx    
                                       xxxxxxxxxxxxxxx       xxx xxxxxx     xx       xx        xxxxxx xxxx    
                                       xxxxxxxxxxxxxxxxxx    xxx xxxxxx     xx       xx        xxxxxx xxxx  
                                       xxxxxxxxxxxxxxxxxx                                                           xxx xxx xxxxx   
                                                                                                                    xxxxxxxxxx xxxxx 
              V: xxxxxxxxx             xxxxxxxxxxxxxxxxxx    xxx xxxxxx     xx       xx        xxxxxx xxxxx         
              D: xxxx-xx-xxTxx:xx:xx                                                                                
                                       xxxxxx   xxxxxxxx     xxx xxxxxx     xx       xx        xxxxxx xxxx    
                                       xxxxxxxxxxxx          xxx xxx        x        xx        xxxxxx xxxx 
                                       xxxxxxxxxxxxxxxxxx    xxx xxx        x        xx        xxxxxx xxxx                             
 
              
 
 
 
______________________________________________________________________________________________________________________________________ 
¹ Clinically Significant per Investigator 
SOURCE: USERNAME\SPONSOR\PROJECT\JOBNAME (DATE, TIME) 
 
Listing sorted by Subject, Visit, Date/Time, and Lab Test. 
 
 


 
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Page 141 of 141  
CONFIDENTIAL 
Repeat Listing 16.2.8.2.1.1: for the following listings: 
 
Listing 16.2.8.3.1.2: Chemistry Laboratory Test Results  
Listing 16.2.8.3.1.3: Urinalysis Laboratory Test Results