Clinical trial NCT02595008
Conditions: Dermatitis, Atopic
Sponsor: Sun Pharmaceutical Industries, Inc.
Start date: 2015-08-28; Completion date: 2017-08-25
Enrollment: 24 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
this study is to evaluate the potential of DSXS to suppress HPA axis function in patients with moderate to severe atopic dermatitis.

Detailed description:
The objective of this study is to evaluate the potential of DSXS to suppress HPA axis function in patients with moderate to severe atopic dermatitis.

The secondary objectives are to evaluate to evaluate adverse event (AE) profiles of DSXS administered to patients with moderate to severe atopic dermatitis.

Arms: arm 1: treatment with DSXS twice daily for 28 days
Interventions: intervention 1: DSXS
Intervention descriptions: intervention 1: Active treatment

Protocol documents:
Prot_000.pdf: 
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SAP_001.pdf: 
NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 1 of 61 
 
STATISTICAL ANALYSIS PLAN                 
 
 
An Open Label, Safety Study to Assess the Potential for Adrenal Suppression Following 
Maximal Use Treatment with Desoximetasone 0.15% Topical Spray (Taro Pharmaceuticals 
U.S.A., Inc.) in Patients with Atopic Dermatitis 
 
 
Protocol Number: DSXS 1502 
Novum Study Number: 71542604 
 
 
Sponsor: 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, 
Hawthorne, NY 10532 
USA 
 
 
Contract Research Organization: 
Novum Pharmaceutical Research Services 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
 
 
January 12, 2016 
Final Version 1.0 
 
 




NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 3 of 61 
Revision History 
VERSION 
DATE 
DESCRIPTION OF REVISIONS 
REVISED BY 
Draft 1.0 
May 10, 2016 
New Document 
Jianhua Liu 
Final 1.0 
January 12, 2017 
Incorporate client comments and finalize SAP 
Jianhua Liu 
 
 
 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 4 of 61 
List of Abbreviations and Definition of Terms 
ADaM  
 
Analysis Data Model 
AE 
 
 
Adverse Event 
BP 
 
 
Blood Pressure 
BSA 
 
 
Body Surface Area 
C 
 
 
Celsius 
CRF 
 
 
Case Report Form 
CDISC 
 
Clinical Data Interchange Standards Consortium 
CRO  
 
Contract Research Organization 
EASI  
 
Eczema Area and Severity Index 
F 
 
 
Fahrenheit 
FDA  
 
Food and Drug Administration 
HR 
 
 
Heart Rate 
Hg 
 
 
Mercury 
HPA  
 
Hypothalamic Pituitary Adrenal 
ICH 
 
 
International Conference on Harmonisation 
IGA 
 
 
Investigator’s Global Assessment 
IND 
 
 
Investigational New Drug 
LOCF  
 
Last Observation Carried Forward 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
ITT 
 
 
Intent-to-Treat 
LOCF  
 
Last Observation Carried Forward 
OGD  
 
The Office of Generic Drugs 
PP 
 
 
Per-Protocol 
SAE 
 
 
Serious Adverse Event 
SAP 
 
 
Statistical Analysis Plan 
SAS 
 
 
Statistical Analysis System 
SDTM  
 
Study Data Tabulation Model 
USA  
 
United States of America 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 5 of 61 
TABLE OF CONTENTS 
1. INTRODUCTION .......................................................................................................................7 
2. OBJECTIVES ..............................................................................................................................7 
3. OVERALL STUDY DESIGN .....................................................................................................7 
4. RANDOMIZATION AND BLINDING....................................................................................10 
5. SAMPLE SIZE ..........................................................................................................................10 
6. STUDY ENDPOINTS ...............................................................................................................10 
7. STATISTICAL ANALYSIS METHODS .................................................................................11 
7.1 Baseline Characteristics ......................................................................................................11 
7.1.1 Subject Disposition .....................................................................................................11 
7.1.2 Demographic and Other Baseline Characteristics .......................................................11 
7.1.3 Medical History ...........................................................................................................12 
7.1.4 Concomitant Medications ...........................................................................................12 
7.1.5 Pregnancy Test ............................................................................................................12 
7.2 Safety Analysis of Potential HPA Axis Suppression ..........................................................12 
7.3 Safety Analysis ...................................................................................................................13 
7.3.1 Adverse Events ............................................................................................................13 
7.3.2 Vital Signs ...................................................................................................................13 
7.3.3 Laboratory Evaluations ...............................................................................................14 
7.3.4 Investigator Global Assessment ..................................................................................14 
7.3.5 Eczema Area and Severity Index Score (EASI) ..........................................................14 
7.3.6 Percent BSA Affected .................................................................................................15 
7.3.7 Pruritus Assessment ....................................................................................................15 
7.4 Multiple Comparisons .........................................................................................................15 
7.5 Methods for Handling Missing Data ...................................................................................15 
7.6 Interim Analyses .................................................................................................................15 
8. TABLE, LISTING AND FIGURE SHELLS ............................................................................15 
T16.1.9.1 Summary of Enrolled Patients ..................................................................................17 
T16.1.9.2 Summary of Protocol Deviations  (Safety Population) ............................................18 
T16.1.9.3 Summary of Patients Randomized, Included in Safety Analysis of Potential 
HPA Axis Suppression by Study Center ...........................................................................19 
T16.1.9.4 Summary of Demographic Data  (Safety Population) ..............................................20 
T16.1.9.5 Summary of Frequency of HPA Axis Suppression at the End of Treatment 
(Day 28) .............................................................................................................................22 
T16.1.9.5a Summary of Logistic Regression Analysis Results of HPA Axis 
Suppression at the End of Treatment (Day 28) ..................................................................23 
T16.1.9.6 Summary of Percent BSA Affected with Plaque Psoriasis  (Safety 
Population) .........................................................................................................................24 
T16.1.9.7 Summary of Frequency of Investigator Global Assessment (IGA) (Safety 
Population) .........................................................................................................................25 
T16.1.9.8 Summary of Total Score - Eczema Area and Severity Index (EASI) (Safety 
Population) .........................................................................................................................26 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 6 of 61 
T16.1.9.9 Overall Summary of Adverse Events (Safety Population) .......................................27 
T16.1.9.10.1 Summary of Frequency of All Adverse Events by Body System  (Safety 
Population) .........................................................................................................................28 
T16.1.9.10.2 Summary of Frequency of All Adverse Events in ≥ 2% of Patients by 
Body System  (Safety Population) .....................................................................................28 
T16.1.9.11 Summary of Frequency of All Adverse Events by Severity (Safety 
Population) .........................................................................................................................29 
T16.1.9.12 Summary of Frequency of All Adverse Events by Relationship (Safety 
Population) .........................................................................................................................30 
T16.1.9.13 Summary of Frequency of Serious Adverse Events (Safety Population) ...............31 
T16.1.9.14 Summary of Adverse Events by Treatment  (Safety Population) ...........................32 
T16.1.9.15 Summary of Shift Analysis of Clinical Laboratory Assessments 
(Chemistry) from Baseline to Day 28 (Safety Population) ................................................33 
T16.1.9.16 Summary of Shift Analysis of Clinical Laboratory Assessments 
(Hematology) from Baseline to Day 28 (Safety Population) .............................................33 
T16.1.9.17 Summary of Frequency of Pruritis Assessment  (Safety Population) ....................34 
L16.2.1 Listing of Discontinued Patients ..................................................................................35 
L16.2.2 Listing of Protocol Deviations .....................................................................................36 
L16.2.3 Patients Excluded from Safety Analysis of Potential HPA Axis Suppression ............37 
L16.2.4.1 Listing of Demographic Data ...................................................................................38 
L16.2.4.2 Listing of Medical History .......................................................................................39 
L16.2.4.3 Listing of Concomitant Medication ..........................................................................40 
L16.2.5.1 Listing of Drug Administration ................................................................................41 
L16.2.5.2 Listing of Study Medication Weight ........................................................................42 
L16.2.6.1 Listing of Cortisol Response Test Results ................................................................43 
L16.2.6.2 Listing of HPA Axis Suppression Follow-Up ..........................................................44 
L16.2.6.3 Listing of Investigator Global Assessment (IGA) ....................................................45 
L16.2.6.4 Listing of Percent BSA Affected with Plaque Psoriasis ...........................................46 
L16.2.6.5 Listing of Eczema Area and Severity Index (EASI) ................................................47 
L16.2.6.6 Listing of Pruritis Assessment ..................................................................................48 
L16.2.7 Listing of Adverse Events by Cohort ..........................................................................49 
L16.2.8.1 Listing of Positive Pregnancy Test Results ..............................................................50 
L16.2.8.2 Listing of Abnormal Vital Signs ..............................................................................51 
L16.2.8.3 Listing of Abnormal Physical Examination Results .................................................52 
L16.2.8.4 Listing of Clinical Hematology Laboratory Results .................................................53 
L16.2.8.5 Listing of Clinical Chemistry Laboratory Results ....................................................54 
10. APPENDICES .........................................................................................................................55 
APPENDIX A:  Body Surface Area Calculation ......................................................................55 
APPENDIX B:  Eczema Area and Severity Index Score (EASI) .............................................57 
APPENDIX C:  Investigator Global Assessment (IGA)...........................................................59 
APPENDIX D:  Cortisol Response Test ...................................................................................60 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 7 of 61 
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the final Clinical Study Protocol DSXS 1502 
(Novum Study No. 71542604) Rev. 6 dated 09/06/2016. The SAP provides details on the 
planned statistical methodology for the analysis of the study data. The SAP also outlines the 
statistical programming specifications for the tables, listings and figures. 
This SAP describes the study endpoints, derived variables, anticipated data transformations and 
manipulations, and other details of the analyses not provided in the study protocol. This SAP 
therefore outlines in detail all other aspects pertaining to the planned analyses and 
presentations for this study. 
The following documents were reviewed in preparation of this SAP: 
 Final Clinical Study Protocol DSXS 1502 (Novum Study No. 71542604) Rev. 6 dated 
09/06/2016 
 Case Report Form Version 1.0 for Novum Study No. 71542604 dated 10/07/2015 
The reader of this SAP is encouraged to also read the clinical protocol for details on the 
conduct of this study, and the operational aspects of clinical assessments and timing for 
completing a patient in this study. 
2. OBJECTIVES 
1. The primary objective of this study is to evaluate the potential of desoximetasone 
0.15% topical spray to suppress HPA axis function in patients with moderate to severe 
atopic dermatitis. 
2. The secondary objectives are to evaluate the efficacy parameters and adverse event 
(AE) profile of desoximetasone 0.15% topical spray administered to patients with 
moderate to severe atopic dermatitis. 
3. OVERALL STUDY DESIGN 
This open label, safety study is designed to evaluate the potential for adrenal suppression after 
maximal use treatment with desoximetasone 0.15% topical spray (Taro Pharmaceuticals, 
U.S.A.), for the treatment of moderate to severe atopic dermatitis. 
 
Up to 70 eligible patients with atopic dermatitis that satisfy all eligibility criteria will be enrolled 
into the study at Visit 2. Patients must be overall in good health. They should have a current 
diagnosis of moderate to severe atopic dermatitis with IGA score of at least 3 or 4. 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 8 of 61 
Up to seventy (70) patients stratified by age with a confirmed diagnosis of moderate to severe 
atopic dermatitis with: 
 
Cohort 1- 10-20 patients age 18 years and older with ≥ 25% body surface area (BSA) affected 
Cohort 2- 10 -20 patients age 12-17 years of age with ≥ 25% body surface area (BSA) affected 
Cohort 3- 5-l 0 patients age 6-11 years of age with ≥ 35% body surface area (BSA) affected 
Cohort 4- 5-l 0 patients age 2-5 years of age with with ≥ 35% body surface area (BSA) affected 
Cohort 5- 5-l 0 patients 6 months to 1 year of age with ≥ 35% body surface area (BSA) affected 
 
Cohorts will be enrolled in sequential order. Each cohort will initiate enrollment once the 
previous cohort has reached the minimum number of patients and a safety analysis has been 
reviewed. Each cohort will be enrolled based on the availability of patients. 
 
Each cohort will be reviewed for the potential of HPA axis suppression. If at least 50% of 
patients in each cohort experience HPA axis suppression once the minimum number of patients 
has been enrolled and completed the cohort, enrollment for that cohort will be stopped and no 
further cohorts will be initiated. If at least 35% of patients have experienced HPA axis 
suppression across cohorts combined during the study, enrollment will be discontinued and no 
other cohorts will be initiated. Cohort 2 will not begin until safety data has been reviewed for 
Cohort 1. The same process will be followed for each cohort until the study is complete. 
 
Patients enrolled in the study will apply product twice a day, according to provided instructions, 
for a total of 28 days. 
 
Patients will attend a total of 4 Clinic Visits as follows: 
 
• 
Visit 1 (within 10 days prior to enrollment): Screening 
 
• 
Visit 2 (Day 1): Enrollment 
 
• 
Visit 3 (Day 14±2): Interim Visit 
 
• 
Visit 4 (Day 28±2): End of Study or Early Termination 
 
 
 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 9 of 61 
  Figure 1 Study Schematic 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Day 
(-10 to 0) 
1 
14 ± 2 
28 ± 2 
42 ± 4 
Procedures 
Screening 
(within 10 days 
before enrollment) 
Before 12 pm 
Enrollment 
Interim 
Visit 
End of 
Study/Early 
Termination 
Before 12 pm 
Telephone 
Follow-Up 
Visit 
Informed Consent 
X 
 
 
 
 
Medical History and 
Demographics 
X 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
 
Pregnancy Test* 
X 
X 
X 
X 
 
Physical Exam 
X 
 
 
X 
 
% BSA Assessment 
X 
X 
X 
X 
 
IGA Score 
X 
X 
X 
X 
 
EASI Score 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
 
Laboratory Evaluations 
X 
 
 
X 
 
Cortisol Response Test 
X 
 
 
X 
 
Confirm Inclusion/Exclusion 
Criteria 
X 
X 
 
 
 
Dispense Sunscreen and 
Wristband 
 
X 
 
 
 
Weigh and Dispense Study 
Drug 
 
X 
X 
 
 
Collect and Weigh Study 
Drug 
 
 
X 
X 
 
Dispense/Review Patient 
Diary 
 
X 
X 
X 
 
Adverse Events 
 
 
X 
X 
X 
Evaluation of Patient 
Compliance to the Protocol 
 
 
X 
X 
 
* Pregnancy test will be carried out for females of childbearing potential. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 10 of 61 
4. RANDOMIZATION AND BLINDING 
Patients eligible for enrollment into the study will fall into one of five cohorts: 
Cohort 1- 10-20 patients age 18 years and older with ≥ 25% body surface area (BSA) affected 
Cohort 2- 10 -20 patients age 12-17 years of age with ≥ 25% body surface area (BSA) affected 
Cohort 3- 5-l 0 patients age 6-11 years of age with ≥ 35% body surface area (BSA) affected 
Cohort 4- 5-l 0 patients age 2-5 years of age with with ≥ 35% body surface area (BSA) affected 
Cohort 5- 5-l 0 patients 6 months to 1 year of age with ≥ 35% body surface area (BSA) affected 
At Visit 2 eligible patients will be enrolled to the study and assigned a patient number. 
Cohorts will be enrolled in sequential order.  Each cohort will initiate enrollment once the 
previous cohort has reached the minimum number of patients and a safety analysis has been 
reviewed.  Each cohort will be enrolled based on the availability of patients. 
Each cohort will be reviewed for the potential of HPA axis suppression. If at least 50% of 
patients in each cohort experience HPA axis suppression once the minimum number of patients 
has been enrolled and completed the cohort, enrollment for that cohort will be stopped and no 
further cohorts will be initiated.  If at least 35% of patients have experienced HPA axis 
suppression across cohorts combined during the study, enrollment will be discontinued and no 
other cohorts will be initiated.  Cohort 2 will not begin until safety data has been reviewed for 
Cohort 1.  The same process will be followed for each cohort until the study is complete.   
5. SAMPLE SIZE 
The sample size of 70 patients, stratified by age and % BSA, was based on recommendations of 
the FDA in IND 101789 Guidance Meeting that took place on 01/14/2015 and FDA Advice 
Letter dated 04/27/2015 (Reference 103740601). 
6. STUDY ENDPOINTS 
Primary Outcome Measures: 
Hypothalamic Pituitary Adrenal (HPA) Axis Response to Cosyntropin demonstrating the absence 
or presence of adrenal suppression at the end of treatment. 
 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
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Secondary Outcome Measures: 
Hypothalamic Pituitary Adrenal (HPA) Axis Response to Cosyntropin demonstrating the 
presence of adrenal suppression at the end of treatment with %BSA as a covariate. %BSA will 
be assessed using instructions in Appendix A. 
7. STATISTICAL ANALYSIS METHODS 
If not otherwise specified, statistical significance is defined as p<0.05 and is two-tailed. Data 
will be summarized with respect to demographic and baseline characteristics and safety 
variables. 
For categorical variables, the number and percent of each category within a parameter will be 
calculated for non-missing data. For continuous variables, statistics will include n, mean, standard 
deviation, median, minimum and maximum values. 
All statistical analyses will be conducted using SAS®, Version 9.4 or higher. Datasets will be prepared 
using headings from Clinical Data Interchange Consortium (CDISC) Study Data Tabulation Model 
(SDTM) implementation for human clinical trials and ADaM (Analysis Dataset Model). 
7.1 Baseline Characteristics 
7.1.1 Subject Disposition 
The subject accountability and disposition information will be summarized by study cohort. The 
number of subjects enrolled, treated with study medication will be tabulated by study cohort. In 
addition, completion status and primary reason for withdrawal will be summarized by study cohort. 
7.1.2 Demographic and Other Baseline Characteristics 
The cohorts will be compared for basic demographics (age, gender, ethnicity and race), baseline 
IGA, baseline EASI and baseline total BSA.  
Summary tables by cohort will be presented. Continuous variables will be summarized using 
descriptive statistics (n, mean, standard deviation, median, minimum, maximum). Categorical 
variables will be summarized using frequencies and percentage.  
Baseline comparability of the five cohorts will be presented using Chi-square test for the 
categorical variables, and Analysis of Variance for the continuous variables. 
All data will be listed by cohort and patient. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
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01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 12 of 61 
7.1.3 Medical History 
At Visit 1, patients will be questioned about medical history, including acute and chronic 
medical history and medical history relevant to their atopic dermatitis, as well as all medication 
use within the past 12 weeks. 
Medical history data will be listed by cohort and patient. 
7.1.4 Concomitant Medications 
At Visits 1-4, patients will be questioned about current and concomitant medication over the past 
12 weeks. 
All prior and concomitant medications taken since screening until the end of the study will be 
listed by cohort and patient. 
7.1.5 Pregnancy Test 
Urine pregnancy tests on women of child-bearing potential will be performed at Visits 1, 2, 3 and 
4. 
Positive pregnancy test results will be listed by cohort and patient. 
7.2 Safety Analysis of Potential HPA Axis Suppression 
Dosing will be twice a day for 28 days excluding the doses prior to the Cortisol Response Test 
(54 applications).  All patients who are enrolled, use at least 42 doses of the study drug and have 
data from a post-treatment cortisol response test will be included in the analysis.  Patients who 
have not used 42 doses of the study drug will be excluded from the primary analysis of HPA axis 
suppression. 
The primary analysis of interest is the proportion of patients in each cohort who are considered to 
have demonstrated possible HPA axis suppression following treatment with the study 
medicationA logistic regression of the proportion of patients in the study with HPA axis 
suppression may be performed as exploratory analysis with % BSA affected as a covariate.  This 
will depend on the distribution of the %BSA data collected.  See Appendix D for results from the 
cortisol response test considered indicative of potential HPA axis suppression. 
Cohorts will be enrolled in sequential order.  Each cohort will initiate enrollment once the 
previous cohort has reached the minimum number of patients and a safety analysis has been 
reviewed.  Each cohort will be enrolled based on the availability of patients. 
Each cohort will be reviewed for the potential of HPA axis suppression. If at least 50% of 
patients in each cohort experience HPA axis suppression once the minimum number of patients 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 13 of 61 
has been enrolled and completed the cohort, enrollment for that cohort will be stopped and no 
further cohorts will be initiated.  If at least 35% of patients have experienced HPA axis 
suppression across cohorts combined during the study, enrollment will be discontinued and no 
other cohorts will be initiated.  Cohort 2 will not begin until safety data has been reviewed for 
Cohort 1.  The same process will be followed for each cohort until the study is complete. 
7.3 Safety Analysis 
Safety analysis will be conducted on all patients who applied at least one dose of study drug.   
7.3.1 Adverse Events 
All the adverse events (AEs) reported throughout the study will be coded and classified 
according to the MedDRA (Medical Dictionary for Regulatory Activities) coding dictionary 
(Version 17.0 or higher). Each adverse event is to be evaluated for date of start and end, 
seriousness, severity, causal relationship with the study drugs, action taken and outcome. 
A summary table of the number and percent of patients with AEs by system organ class, 
preferred term, and cohort will be presented. Each patient will be counted only once within each 
preferred term. 
A frequency summary table of the number of AEs by system organ class, preferred term, 
severity, and cohort will be presented. Severity will be classified as “Mild”, “Moderate”, or 
“Severe”. 
Similarly, a frequency summary table of the number of AEs by system organ class, preferred 
term, and relationship to a study drug, and cohort will be presented. Relationship to a study drug 
will be classified as “Not Related” or “Related” where “Related includes “Possible”, “Probable”, 
or “Definite”. 
Should sufficient data exist, adverse event frequencies will be compared between treatments 
using Fisher’s exact test. 
All AEs will be listed by cohort and patient. 
7.3.2 Vital Signs 
The patient’s vital signs will be recorded (heart rate, blood pressure, temperature and respiration 
rate) at Visit 1, 2, 3 and 4. 
Abnormal vital signs will be listed by cohort and patient. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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01/12/2017 
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Page 14 of 61 
7.3.3 Laboratory Evaluations 
At Visit 1 and Visit 4 a blood sample will be collected for hematology and clinical chemistry 
testing. The testing panel should include as a minimum the following tests: 
Hematology 
 Hematocrit  
 White blood cell count 
 Platelets 
 Hemoglobin 
 Red blood cell count  
 Differential white cell count 
Chemistry 
 Alkaline phosphatase  
 Total bilirubin 
 Alanine transaminase  
 Creatinine 
 Aspartate transaminase  
 Glucose 
 Blood urea nitrogen 
Shift analysis using the categories; below, above and within the laboratory normal range will be 
performed to identify any specific laboratory parameter that shows a trend toward potentially 
clinically significant changes. 
All data will be listed by cohort and patient. 
7.3.4 Investigator Global Assessment 
At Visit 1 a visual inspection to confirm a diagnosis of chronic plaque psoriasis will be done.  At 
each visit the Investigator will perform an Investigator Global Assessment (IGA).  At Visit 1 the 
patient must have an IGA of 3 (moderate) or 4 (severe) for inclusion in the study. 
Investigator Global Assessment will be summarized using frequency and percentage by cohort 
and visit. 
Investigator Global Assessment will also be listed by cohort and patient. 
7.3.5 Eczema Area and Severity Index Score (EASI) 
Eczema Area and Severity Index Score will be assessed at each visit. 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
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01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 15 of 61 
EASI will be summarized using frequency and percentage by cohort and visit. EASI will also be 
listed by cohort and patient. 
 7.3.6 Percent BSA Affected 
The % BSA recorded at Visit 1, 2, 3 and 4 will be summarized descriptively by cohort and visit.  
All data will be listed by cohort and patient. 
7.3.7 Pruritus Assessment 
A frequency summary table comparing the severity of pruritus for each cohort will be presented 
by visit. 
All data will be listed by cohort and patient. 
7.4 Multiple Comparisons 
No multiple comparison adjustment will be made in this study. 
7.5 Methods for Handling Missing Data 
For demographic and baseline characteristics, each variable will be analyzed using all available 
data. Patients with missing data will be excluded only from analyses for which data are not 
available. 
7.6 Interim Analyses 
There is no interim analysis planned in this study. 
8. TABLE, LISTING AND FIGURE SHELLS 
The following shells are provided in order to provide a framework for the display of data from 
this study. These shells may not be reflective of every aspect of this study but are intended to 
show the general layout of the Tables, Listings and Figures that will be included in the final 
clinical study report. Tables, Listings and Figures are numbered following the ICH structure. 
Table headers, variables names and footnotes will be modified as needed following data 
analyses. All descriptive and inferential statistical analyses will be performed using SAS® 
statistical software Version 9.4 or higher, unless otherwise noted. 


 
Taro Pharmaceuticals U.S.A., Inc 
Novum Pharmaceutical Research Services 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 16 of 61 
 
 
 
 
 
 
 
TABLE, LISTING AND FIGURE SHELLS 
 
 


 
Taro Pharmaceuticals U.S.A., Inc 
Novum Pharmaceutical Research Services 
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Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
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Page 17 of 61 
T16.1.9.1 Summary of Enrolled Patients 
 
Patients 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Cohort 5 
Total 
Screened 
 
 
 
 
 
xxx 
Randomized 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Completed Study 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Terminated Early 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
Early Termination Reason 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Adverse Event 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Enrolled in error 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Insufficient therapeutic response/treatment failure 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Lost to follow-up 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
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Taro Pharmaceuticals U.S.A., Inc 
Novum Pharmaceutical Research Services 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 18 of 61 
T16.1.9.2 Summary of Protocol Deviations  
(Safety Population) 
 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Cohort 4 
Cohort 5 
Total 
Total Patients with Protocol Deviations 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Total Deviations 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
Enrolled in Error 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Lost to Follow-up 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Missed Visit 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Non-compliance with dosing requirements 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Outside Visit Window 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
Restricted Medication Use 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
etc 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
 
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Taro Pharmaceuticals U.S.A., Inc 
Novum Pharmaceutical Research Services 
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Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 19 of 61 
T16.1.9.3 Summary of Patients Randomized, Included in Safety Analysis of Potential HPA Axis Suppression by Study Center 
Site 
No. 
PI Name 
Total 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Cohort 5 
Rando- 
mized Included Rando- 
mized 
Included 
Rando- 
mized 
Included Rando- 
mized 
Included Rando- 
mized 
Included 
Rando- 
mized 
Included 
All 
- 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xx 
xxxx 
xx 
xx (xx.x%)
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xxxx 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
xx 
xx(xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Taro Pharmaceuticals U.S.A., Inc 
Novum Pharmaceutical Research Services 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 20 of 61 
T16.1.9.4 Summary of Demographic Data  
(Safety Population) 
 
 
Cohort 1 
N=xx 
Cohort 2 
N=xx 
Cohort 3 
N=xx 
Cohort 4 
N=xx 
Total 
N=xx 
P-value 
Age (years) 
n 
xx 
xx 
xx 
xx 
xx 
x.xxxx 
 
Mean ± SD 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
 
Age Groups 
2 – 11  
- 
- 
- 
xx (100.0%) 
- 
 
 
12 – 15  
- 
- 
xx (100.0%) 
- 
- 
 
 
16 – 17  
- 
xx (xx.x%) 
- 
- 
- 
 
 
18 – 19  
- 
xx (xx.x%) 
- 
- 
- 
- 
 
19 – 40 
xx (xx.x%) 
- 
- 
- 
- 
 
 
41 – 64 
xx (xx.x%) 
- 
- 
- 
- 
 
 
65 – 75 
xx (xx.x%) 
- 
- 
- 
- 
 
 
> 75 
xx (xx.x%) 
- 
- 
- 
- 
 
Race 
American Indian or Alaska Native 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
 
Asian 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Black/African American 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Native Hawaiian or other Pacific 
Islander 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
White 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Other 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Ethnicity 
Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
 
Not Hispanic or Latino 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
N= number of patients in the cohort; n= number of patient with data available; % is based on N 
 
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Novum Pharmaceutical Research Services 
Desoximetasone 0.15% Topical Spray 
Protocol / Study No. DSXS 1502 / 71542604 
 
 
01/12/2017 
 Taro Pharmaceuticals U.S.A., Inc  
Page 21 of 61 
T16.1.9.4 Summary of Demographic Data 
(Safety Population) 
 
 
Cohort 1 
N=xx 
Cohort 2 
N=xx 
Cohort 3 
N=xx 
Cohort 4 
N=xx 
Cohort 5 
N=xx 
Total 
N=xx 
P-value 
Baseline Total BSA  
n 
xx 
xx 
xx 
xx 
xx 
xx 
x.xxxx 
 
Mean ± SD 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
 
Baseline IGA 
Clear 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
x.xxxx 
Almost Clear 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
EASI 
n 
xx 
xx 
xx 
xx 
xx 
xx 
x.xxxx 
 
Mean ± SD 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
xx.x ± x.x 
 
 
Median 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Range 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
xx-xx 
 
 
 
 
 
 
 
 
 
 
N= number of patients in the cohort; n= number of patient with data available; % is based on N 
 
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T16.1.9.5 Summary of Frequency of HPA Axis Suppression at the End of Treatment (Day 28) 
 
HPA Axis 
Suppression 
All 
N=xx 
Cohort 1 
N=xx 
Cohort 2 
N=xx 
Cohort 3 
N=xx 
Cohort 4 
N=xx 
Cohort 5 
N=xx 
Yes 
No 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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T16.1.9.5a Summary of Logistic Regression Analysis Results of HPA Axis Suppression at the End of Treatment (Day 28)  
 
Odds Ratio 
95% Wald 
Confidence Limits 
Wald 
Chi-Square 
P-value 
Cohort 1 vs. Cohort 2 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 1 vs. Cohort 3 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 1 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 1 vs. Cohort 5 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 2 vs. Cohort 3 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 2 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 2 vs. Cohort 5 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 3 vs. Cohort 4 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 3 vs. Cohort 5 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Cohort 4 vs. Cohort 5 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
Baseline % BSA affected 
x.xxxx 
x.xxxx, x.xxxx 
x.xxxx 
x.xxxx 
 
 
 
 
 
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T16.1.9.6 Summary of Percent BSA Affected with Plaque Psoriasis  
(Safety Population) 
Visit 
Statistic 
Cohort 1 
(N = xx) 
Cohort 2 
(N = xx) 
Cohort 3 
(N = xx) 
Cohort 4 
(N = xx) 
Cohort 5 
(N = xx) 
1 
n 
xx 
xx 
xx 
xx 
xx 
 
Mean ± SD 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
Range 
xxx - xxx 
xxx – xxx 
xxx - xxx 
xxx - xxx 
xxx - xxx 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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T16.1.9.7 Summary of Frequency of Investigator Global Assessment (IGA) 
(Safety Population) 
Visit 
Score 
Cohort 1 
(N = xx) 
Cohort 2 
(N = xx) 
Cohort 3 
(N = xx) 
Cohort 4 
(N = xx) 
Cohort 5 
(N = xx) 
1 
0 (Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
1 (Almost Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
2 (Mild Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
3 (Moderate 
Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4 (Severe Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 
0 (Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
1 (Almost Clear) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
2 (Mild Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
3 (Moderate 
Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
4 (Severe Disease) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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T16.1.9.8 Summary of Total Score - Eczema Area and Severity Index (EASI) 
(Safety Population) 
Visit 
Statistic 
Cohort 1 
(N = xx) 
Cohort 2 
(N = xx) 
Cohort 3 
(N = xx) 
Cohort 4 
(N = xx) 
Cohort 5 
(N = xx) 
1 
n 
xx 
xx 
xx 
xx 
xx 
 
Mean ± SD 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
xxx.x ± xx.x 
 
Median 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
xxx.x 
 
Range 
xxx - xxx 
xxx – xxx 
xxx - xxx 
xxx - xxx 
xxx - xxx 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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T16.1.9.9 Overall Summary of Adverse Events 
(Safety Population)  
Description 
Cohort 1 
N=xx 
Cohort 2 
N=xx 
Cohort 3 
N=xx 
Cohort 4 
N=xx 
Cohort 5 
N=xx 
Total 
N=xx 
Patients Randomized 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
  Patients with at least one AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Discontinued study drug due to above AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
AEs reported 
xxx 
xxx 
xxx 
xxx 
xxx 
xxx 
  Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Not Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Related 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Death 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  Serious AE 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Related = Possible, Probable, Definite 
 
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T16.1.9.10.1 Summary of Frequency of All Adverse Events by Body System  
(Safety Population) 
Body System 
MedDRA Term 
Cohort 
Events 
Patients 
Fisher’s 
p-value 
Patients with at least one AE 
Total 
Cohort 1 (N=xx) 
xx 
xx (xx.x%) 
x.xxxx 
 
 
Cohort 2 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 3 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 4 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 5 (N=xx) 
xx 
xx (xx.x%) 
 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
xx 
xx (xx.x%) 
x.xxxx 
 
 
Cohort 2 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 3 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 4 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
Cohort 5 (N=xx) 
xx 
xx (xx.x%) 
 
 
 
 
 
 
 
N = Total number of patient in each cohort; Percentage is based on total number of patients. 
 
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T16.1.9.10.2 Summary of Frequency of All Adverse Events in ≥ 2% of Patients by Body System  
(Safety Population) 
 
 
 


 
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T16.1.9.11 Summary of Frequency of All Adverse Events by Severity 
(Safety Population)  
Body System 
MedDRA Term 
Cohort 
Mild 
Moderate 
Severe 
Patients with at least one AE 
Total 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 5 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 5 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
N = Total number of events in each cohort; Percentage is based on total number of events. 
 
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T16.1.9.12 Summary of Frequency of All Adverse Events by Relationship 
(Safety Population)  
Body System 
MedDRA Term 
Cohort 
Related 
Not Related 
Patients with at least one AE 
Total 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 5 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
Ear and labyrinth disorders 
Ear pain 
Cohort 1 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 2 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 3 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 4 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
Cohort 5 (N=xx) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
N = Total number of events in each cohort; Percentage is based on total number of events. 
Related = Possible, Probable, Definite 
 
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T16.1.9.13 Summary of Frequency of Serious Adverse Events 
(Safety Population)  
Body System 
MedDRA 
Term 
Cohort 1 
N=xx 
Cohort 2 
N=xx 
Cohort 3 
N=xx 
Cohort 4 
N=xx 
Cohort 5 
N=xx 
Injury, poisoning and procedural 
complications 
Alcohol 
poisoning 
xx 
xx 
xx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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T16.1.9.14 Summary of Adverse Events by Treatment  
(Safety Population) 
Cohort 1 
 
Severity 
 
Relationship to Study Drug 
Body System 
    MedDRA Term 
Mild 
n (%) 
Moderate  
n (%) 
Severe  
n (%) 
 
Related  
n (%) 
Not Related  
n (%) 
Total AEs (N=xxx) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
Ear and labyrinth disorders 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
     Ear pain 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
     Hypoacusis 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N = Total AEs in Cohort 1; n (%) = Number of AEs (Percent of Total AEs in Cohort 1) 
Related = Possible, Probable, Definite 
 
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Programming Note: Similar tables will be created for other cohorts. 
 


 
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T16.1.9.15 Summary of Shift Analysis of Clinical Laboratory Assessments (Chemistry) from Baseline to Day 28 
(Safety Population) 
Alanine Aminotransferase (U/L) 
 
Cohort 1 
(N=xx) 
Cohort 2 
(N=xx) 
Cohort 3 
(N=xx) 
Cohort 4 
(N=xx) 
Cohort 5 
(N=xx) 
Baseline-> 
Endpoint 
Low 
Normal 
High 
Low 
Normal 
High 
Low 
Normal 
High 
Low Normal High 
Low Normal High  
Low 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
Normal 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
High 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
xx 
(xx.x%) 
 
 
Table will continue for other lab parameters. 
Similar table will be created for T16.1.9.18. 
 
T16.1.9.16 Summary of Shift Analysis of Clinical Laboratory Assessments (Hematology) from Baseline to Day 28 
(Safety Population) 
 
 


 
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T16.1.9.17 Summary of Frequency of Pruritis Assessment  
(Safety Population) 
Visit 
Score 
Cohort 1 
(N = xx) 
Cohort 2 
(N = xx) 
Cohort 3 
(N = xx) 
Cohort 4 
(N = xx) 
Cohort 5 
(N = xx) 
1 
None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
2 
None 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Mild 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Moderate 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Severe 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.1 Listing of Discontinued Patients 
Cohort 
Patient 
Number 
Discontinuation 
Reason 
Cohort 1 
xx-xxxx 
Withdrawal by Subject 
 
xx-xxxx 
Lost to Follow-up 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
Cohort 3 
 
 
Cohort 4 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.2 Listing of Protocol Deviations 
 
Cohort 
Patient 
Number 
Event Description 
Cohort 1 
xx-xxxx 
Outside Visit Window (Visit 3) 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
Cohort 3 
 
 
Cohort 4 
 
 
Cohort 5 
 
 
 
 
 
 
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L16.2.3 Patients Excluded from Safety Analysis of Potential HPA Axis Suppression 
 
Cohort 
Patient 
Number 
Exclusion Reason 
Cohort 1 
xx-xxxx 
Patient has not used 42 doses of the study drug 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
Cohort 3 
 
 
Cohort 4 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.4.1 Listing of Demographic Data 
 
Cohort 
Patient 
Number 
Age 
Gender 
Ethnicity 
Race 
Cohort 1 
xx-xxxx 
30 
Female 
Not Hispanic or Latino 
Black or African American 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.4.2 Listing of Medical History 
 
Cohort 
Patient 
Number 
System 
Diagnosis or 
Surgical 
Procedure 
Start Date 
End Date 
Ongoing 
Cohort 1 
xx-xxxx 
Gynecologic 
Menopause 
yyyy-mm-dd 
yyyy-mm-dd 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.4.3 Listing of Concomitant Medication 
 
Cohort 
Patient 
Number 
Treatment 
Area 
Medication 
Dosage 
Frequency Route 
Start/End 
Date 
Indication 
Cohort 1 
xx-xxxx 
No 
Lisinopril 
20 MG 
QD 
PO 
yyyy-mm-dd / 
yyyy-mm-dd 
Hypertension 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.5.1 Listing of Drug Administration 
 
Cohort 
Patient 
Number 
Date of 
First Dose 
Date of 
Last Dose 
Total 
Doses Applied 
Compliance 
(%) 
Cohort 1 
xxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Note to programmer: 
Compliance = [Total number of applications] / [Planned number of applications] * 100%, where Planned number of applications is determined as 
follows:  
           for subjects who completed the study successfully: 56 applications (28 days of twice daily dosing);  
           for subjects who discontinued early:  the minimum between 56 and [(Date of Discontinuation – Date of First Application)].  
 
 
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L16.2.5.2 Listing of Study Medication Weight 
 
Cohort 
Patient 
Number 
Bottle 1 
 
Bottle 2 
 
Total 
 Amount  
Applied 
(g) 
Date  
Dispensed 
Weight  
Dispensed 
(g) 
 
Date  
Collected 
Weight  
Collected 
(g) 
Cohort 1 
xxxx 
yyyy-mm-dd 
xx 
 
yyyy-mm-dd 
xx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.6.1 Listing of Cortisol Response Test Results 
 
Cohort 1 
 
Patient 
Number 
 
 
Visit  
 
Was a Cortisol 
Response Test 
conducted? 
 
 
Date 
 
 
Basal 
Sample 
Draw Time  
 
 
Injection 
Time 
 
 
Post-
Injection 
Draw  
Time 
Basal  
Cortisol 
Concentration 
Level 
(mcg/100ml) 
Post Injection 
Cortisol 
Concentration 
Level 
(mcg/100ml) 
 
Have 
Abnormal 
Adrenal 
Function? 
 
Have  
HPA Axis 
Suppression
? 
xx-xxxx 
1 
Yes 
yyyy-mm-dd 
hh:mm 
hh:mm 
hh:mm 
xxx 
xxx 
No 
 
 
4 
Yes 
yyyy-mm-dd 
hh:mm 
hh:mm 
hh:mm 
xxx 
xxx 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table will continue for other cohorts. 
 
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L16.2.6.2 Listing of HPA Axis Suppression Follow-Up  
Cohort 1 
 
Patient 
Number 
Is The Patient Showing Signs  
Or Symptoms Of HPA Axis 
Suppression?/ 
Was a  Cortisol Response  
Test Conducted? 
 
 
Follow-Up 
Test 
Date/ 
Basal Sample Draw Time/  
Injection Time/ 
Post-Injection Draw Time 
Basal 
Cortisol 
Concentration 
Level 
(mcg/100ml) 
Post Injection 
Cortisol 
Concentration 
Level 
(mcg/100ml) 
 
Still Show 
Signs of 
HPA Axis 
Suppression? 
 
Was the  
Patient Referred 
to an 
Endocrinologist 
xx-xxxx 
Yes/ Yes 
Test 1 
yyyy-mm-dd / hh:mm / 
hh:mm/ hh:mm 
xxx 
xxx 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table will continue for other cohorts. 
 
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L16.2.6.3 Listing of Investigator Global Assessment (IGA) 
Cohort 
Patient 
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 / Early 
Termination 
Cohort 1 
xx-xxxx 
0 
0 
1 
0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.6.4 Listing of Percent BSA Affected with Plaque Psoriasis 
Cohort 
Patient 
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 / Early 
Termination 
Baseline Total  
BSA (m^2) 
Cohort 1 
xx-xxxx 
xxx 
xxx 
xxx 
xxx 
x.xx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.6.5 Listing of Eczema Area and Severity Index (EASI) 
Cohort 
Patient 
Number 
Visit 
Location 
Erythema  
 
Induration, 
Papulation, 
Edema  
 
Lichenification  
 
 
Excoriation  
 
 
Total   
Grade 
Total  
EASI  
Score 
Cohort 1 
xx-xxxx 
1 
Head/Neck  
 
0 
0 
0 
0 
0 
xxxx 
 
 
 
Upper Limbs  
 
0 
0 
0 
0 
0 
 
 
 
 
Trunk  
 
1 
1 
1 
1 
4 
 
 
 
 
Lower Limbs  
 
0 
0 
0 
0 
0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.6.6 Listing of Pruritis Assessment 
Cohort 
Patient 
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4/Early 
Termination 
Cohort 1 
xx-xxxx 
0 (None) 
1 (Mild) 
1 (Mild) 
1 (Mild) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.7 Listing of Adverse Events by Cohort 
Cohort 
Patient 
Number 
Body System / 
MedDRA Term / 
AE Term 
Treatmen
t Area 
Start /End 
 Date 
Severity 
Relationship 
to Study 
Drug 
Outcome 
Action Taken/  
Other Action 
Taken 
SAE? 
Cohort 1 
 
 
xx-xxxx 
Nervous system disorders / 
Headache / 
Headache 
No 
yyyy-mm-dd / 
yyyy-mm-dd 
Mild 
Not Related 
Recovered Dose Not Changed/ 
None 
No 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
Cohort 2 
 
 
 
 
 
 
 
 
  
Cohort 3 
 
 
 
 
 
 
 
 
  
Cohort 4 
 
 
 
 
 
 
 
 
  
Cohort 5 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
Related = Possible, Probable, Definite 
 
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L16.2.8.1 Listing of Positive Pregnancy Test Results 
Cohort 
Patient  
Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Cohort 1 
xx-xxxx 
Negative 
Negative 
Negative 
Positive 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.8.2 Listing of Abnormal Vital Signs 
Cohort 
Patient  
Number 
 
Age 
 
Visit 
Vital Sign 
Normal Range 
Result 
Cohort 1 
xx-xxxx 
 
xxx 
1 
 
Diastolic BP 
 
xxx - xxx 
xxx 
 
 
 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.8.3 Listing of Abnormal Physical Examination Results 
Cohort 
Patient  
Number 
Visit 
System 
Results 
Cohort 1 
xx-xxxx 
1 
HEENT 
Abnormal (Scar) 
 
 
 
 
 
 
 
 
 
 
 
 
2 
 
 
 
 
3 
 
 
 
 
4 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
Cohort 3 
 
 
 
 
Cohort 4 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
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L16.2.8.4 Listing of Clinical Hematology Laboratory Results 
Cohort 
Patient  
Number 
Visit 
Hematocrit 
(unit) 
WBC 
(unit) 
Platelets  
(unit) 
Hemoglobin 
(unit) 
etc. 
Cohort 1 
xx-xxxx 
1 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
4 
xxx 
xxx 
xxx 
xxx (Low) 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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L16.2.8.5 Listing of Clinical Chemistry Laboratory Results 
Cohort 
Patient  
Number 
Visit 
Alkaline 
Phosphatase 
(unit) 
Alnine 
Transaminase 
(unit) 
Aspartate 
Transaminase 
(unit) 
Blood Urea 
Nitrogen 
(unit) 
etc. 
Cohort 1 
xx-xxxx 
1 
xxx 
xxx 
xxx (High) 
xxx 
xxx 
 
 
4 
xxx 
xxx 
xxx 
xxx 
xxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cohort 2 
 
 
 
 
 
 
 
Cohort 3 
 
 
 
 
 
 
 
Cohort 4 
 
 
 
 
 
 
 
Cohort 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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NOVUM PHARMACEUTICAL RESEARCH SERVICES 
STATISTICAL ANALYSIS PLAN 
 
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10. APPENDICES 
APPENDIX A:  Body Surface Area Calculation 
Total Body Surface Area Calculation 
To calculate the Total BSA the following procedure (Mosteller Formula13) should be followed. 
Total Body Surface Area (BSA) in meters squared 
m2  = ((height (cm) x weight (kg)) /3600)½ 
 
The patient’s height and weight should be reported to the nearest cm and nearest 0.5 kg. The 
BSA should be reported to the nearest second decimal place. 
For example a patient who is 68 inches tall and weighs 180 lbs will have a reported BSA of: 
68 in x 2.54 = 173 cm 
180 lb x 0.45 = 81.0 kg 
BSA 
= SQRT ((173 x 81.0)/3600) 
= 1.97 m² 
%BSA Affected 
To estimate the % BSA Affected, the Investigator should use the method of approximation: 
The “Rule of Nines” provides a general estimation of total BSA for several anatomic 
areas (each arm = 9%, each leg = 18%, back = 18%, chest and abdomen = 18%, head = 
It is preferable that the patient’s height and weight be 
measured in cm and kg however if needed: 
To convert inches (in) to centimeters (cm) the following 
conversion should be used 
1 inch = 2.54 cm 
To convert pounds (lbs) to kilograms (kg) the following 
conversion should be used 
1 lb = 0.45 kg 


NOVUM PHARMACEUTICAL RESEARCH SERVICES 
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9%, groin = 1%). The Investigator may then visually estimate the proportion of the 
involved skin within each anatomic area and calculate the total percentage of BSA 
affected. In children, hips and legs are smaller and the head, neck and shoulders are 
larger, as a result, a modified “Rule of Nines” is used (see diagram below).  
 
Part 
1-4 year child 
body 
% of total 
5-9 year child 
body 
% of total 
10-14 year child 
body 
% of total 
Adult body 
% of total 
Arm 
9.5% 
9.5% 
9.5% 
9% 
Head
19% 
15% 
12%
9%
Neck 
1% 
1% 
Leg 
15% 
17% 
18% 
18% 
Anterior trunk 
16% 
16% 
16% 
18% 
Posterior trunk 
16% 
16% 
16% 
18% 
 
 


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APPENDIX B:  Eczema Area and Severity Index Score (EASI) 
The EASI is a composite score based on the severity of four different signs of atopic dermatitis in 
four different areas of the body multiplied by the percent of that specific body area affected 
multiplied by a weighting factor.   
 
Erythema 
0 = Clear 
 
 
No evidence of erythema 
1 = Mild 
 
 
Definite light red coloration 
2 = Moderate  
 
Moderate redness, but not dark 
3 = Severe 
 
 
Dark red coloration 
 
Induration/papulation/edema 
 
 
0 = Clear 
 
 
No evidence of any induration/papulation/edema 
1 = Mild 
 
 
Barely perceptible elevation 
2 = Moderate  
 
Clearly perceptible elevation 
3 = Severe 
 
 
Marked and extensive elevation 
 
Lichenification 
0 = Clear 
 
 
No evidence of lichenification 
1 = Mild 
Slight thickening of skin discerible only by touch and with 
skin markings minimally exaggerated 
2 = Moderate 
Definite thickening of skin with skin marking exaggerated so 
at they form a visible criss-cross or ridged pattern 
3 = Severe 
Thickened skin with skin markings visibly portraying an 
exaggerated criss-cross or ridged pattern 
 
Excoriation 
0 = Clear 
 
 
No evidence of excoriation 
1 = Mild 
Scant evidence of excoriation with no signs of deepers skin 
damage (absence of erosion or crusts) 
2 = Moderate 
Several linear marks of skin with some showing evidence of 
deeper skin injury (erosion, crust visible) 
3 = Severe 
 
 
Many erosive or crusty lesions present 
 
The patient will be required to rate the severity of their pruritis (itching/scratching/discomfort) over 
the previous 24 hours using the following scale: 
 
Pruritis 
0 = None 
None 
1 = Mild 
Occasional slight itching or scratching 
2 = Moderate 
Constant or intermittent itching/scratching/discomfort which 
is not disturbing sleep 
 


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3 = Severe 
Bothersome itching/scratching/discomfort which is 
disturbing sleep 
 
Eczema, induration, excoriation and lichenification are part of the EASI score but pruritis is not.   
 
EASI Score  
 
The EASI score is calculated as follows: 
Head/neck 
(E + I + X + L) x Area x 0.1 (in children ages 0-7, x 0.2) 
Upper Limbs (E + I + X + L) x Area x 0.2 
Trunk  
(E + I + X + L) x Area x 0.3 
Lower Limbs (E + I + X + L) x Area x 0.4 (in children ages 0-7, x 0.3) 
EASI SCORE = SUM OF ABOVE 4 REGIONS 
 
E: 
Erythema,  
I:  
Induration/papulation/edema 
X: 
Excoriation 
L: 
Lichenification 
 
Severity is based on the Investigator’s assessment of individual signs and symptoms 
0 = none, 1 = mild, 2 = moderate, 3 = severe using the definitions above 
 
The % of each body region affected is scored as the variable Area above in the 
EASI formula.  For the 4 body regions (head/neck, upper limbs, trunk and lower 
limbs) if the: 
 
Area = 0  
if % affected is 0%  
Area = 1  
if % affected is 1 to 9%  
Area = 2 
if % affected is 10 to 29%  
Area = 3 
if % affected is 30 to 49%  
Area = 4 
if % affected is 50 to 69%  
Area = 5 
if % affected is 70 to 89%  
Area = 6 
if % affected is 90 to 100%  
 
EASI Score can be presented to the nearest whole number (no decimals and all numbers should be 
rounded, 0.5 should be rounded up to the nearest whole number) 
 
The minimum score would be 0 and the Maximum Score would be 72. To be eligible for 
participation in this study a patient must have an EASI of at least 15 at baseline.  
 
 
 


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APPENDIX C:  Investigator Global Assessment (IGA) 
To be eligible for inclusion in the study the IGA must be 3 or 4 at baseline. To be considered a 
Clinical Success the patient must score a 0, 1 at Visit 4. 
 
0 
Clear 
Minor, residual discoloration, no erythema or 
induration/papulation, no oozing/crusting 
1 
Almost Clear 
Just perceptible erythema, with almost no induration/papulation 
and no oozing/crusting 
2 
Mild Disease 
Definite pink erythema with mild induration/papulation and no 
oozing/crusting 
3 
Moderate 
Disease 
Red erythema with moderate induration/papulation and there 
may be some oozing/crusting 
4 
Severe 
Disease 
Dark/bright red erythema with severe induration/papulation 
with oozing/crusting 
 


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APPENDIX D:  Cortisol Response Test 
This cortisol release test is modified from the procedure of Wood et al as described in the 
Product Label for CortrosynTM (cosyntropin) for injection (Amphstar Pharmaceuticals, Inc.). 
The procedure is as follows: 
1. A single 5 ml blood sample should be taken as the basal sample. 
2. 0.25 mg (a single vial) of CortrosynTM (cosyntropin) should be reconstituted with 1.0ml 
of 0.9% sodium chloride injection USP injected intramuscularly. In patients under 3 years 
of age, 0.125mg of CortrosynTM will be used.  
3. 30 minutes after the IM injection a second 5 ml blood sample should be obtained. The 
resulting two serum samples (at least 1 ml of serum in each) should be processed and 
labeled according to the instructions provided and sent the same day to ACM Global 
Laboratory for analysis of basal and post stimulated serum cortisol concentration. 
 
At Visit 1 and Visit 4 all patients will have a cortisol response test performed.  The resulting 
blood sample should be sent to ACM Global Laboratory for immediate testing.  
Visit 1 Test 
The results of the cortisol response test must be obtained prior to study drug being dispensed at 
Visit 2.  Only patients with normal baseline (Visit 1) cortisol and adrenal function  (see 
criteria 
below) should be enrolled in the study. 
Visit 4 Test 
The test at the End of Study visit should not be performed if the patient dosed within 12 hours. 
A patient will be considered to have normal basal cortisol level and adrenal function if they meet 
all three criteria listed below under Normal.  Failure to meet any of these criteria is indicative of 
abnormal adrenal function or potential HPA axis suppression. 
 
Cortisol Results 
Normal 
Abnormal 
Basal 
(pre CortrosynTM 
injection) 
≥ 5 mcg/100ml 
< 5 mcg/100ml 
30 minutes post 
CortrosynTM 
injection 
≥ basal value + 7 
< basal value + 7 
> 18 mcg/100ml 
≤ 18 mcg/100ml 
 
HPA Axis suppression will be defined as a 30 minute post CortrosynTM injection level cortisol 
level of ≤ 18 mcg/100ml. As the study treatment period will be over, any patients with results of 


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HPA axis suppression will be advised not to initiate any new steroid therapy, topical or 
otherwise, and to return to the site in 28 days at which time they will be assessed for HPA axis 
suppression.  
Any patient presenting with symptoms of HPA axis suppression, such as nausea, headache, 
myalgia, fatigue or loose stool, will be referred to an endocrinologist. As an additional safety 
precaution, wristbands identifying the patient as someone suffering from adrenal suppression 
secondary to steroid   withdrawal will be provided to alert medical personnel should any 
emergencies arise before adrenal function returns to normal.  
If the results of the cortisol response test still show signs of HPA axis suppression 28 days after 
discontinuing therapy the patient will be asked to return in 28 days (56 days after discontinuing 
steroid therapy) for another follow-up test. If the patient is still showing signs of HPA axis 
suppression 56 days after discontinuing steroid therapy and presents with related symptoms, the 
patient will be referred to an endocrinologist.  
If HPA axis suppression persists for 56 days after discontinuing steroid therapy, but the patient 
has no symptoms they will be asked to return in 28 days (84 days after discontinuing steroid 
therapy) for another follow-up test. If HPA axis suppression persists for 84 days after 
discontinuing steroid therapy patients will be referred to an endocrinologist regardless of 
symptoms.  
Patients should not be subjected to CortrosynTM testing, or any other challenge to their adrenal 
response, any sooner than 4 weeks from their last CortrosynTM test.  
Follow-Up Schedule for Patients showing signs of HPA Axis Suppression 
Days 
after d/c 
HPA Results 
Symptoms 
Patient Course 
28 
Normal 
N/A 
Study over 
28 
Abnormal 
Yes 
Refer to endocrinologist 
28 
Abnormal 
No 
Repeat test in 28 days 
56 
Normal 
N/A 
Study over 
56 
Abnormal 
Yes 
Refer to endocrinologist 
56 
Abnormal 
No 
Repeat test in 28 days 
84 
Normal 
N/A 
Study over 
84 
Abnormal 
Yes or No 
Refer to an endocrinologist