Conditions: Plaque Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 119
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the therapeutic efficacy and safety of DSXS compared to a Placebo (vehicle) in patients with mild to moderate plaque psoriasis.

Detailed description:
To evaluate the therapeutic efficacy and safety of dsxs topical spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.) compared to a Placebo (vehicle) spray (Taro Pharmaceuticals, U.S.A., Inc.) in patients with mild to moderate plaque psoriasis.

Arms:
arm 1: To evaluate the therapeutic efficacy and safety of DSXS topical spray, 0.15%. arm 2: Eligible patients will be randomized in a 1:1 ratio to Test or Placebo product.

Interventions: intervention 1: DSXS intervention 2: Placebo
Intervention descriptions: intervention 1: active treatment intervention 2: placebo treatment

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 1 of 52 
 
 
1.0 
TITLE PAGE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
This document is a confidential communication of Novum Pharmaceutical Research Services.  Receipt of 
this document constitutes an agreement by the recipient that no unpublished information contained herein 
will be disclosed without Novum's written approval. 
Drug Product 
Desoximetasone Spray, 0.15% 
 
Population 
Up to 120 patients (12 years of age and older) with mild to 
moderate plaque psoriasis 
Study Design 
Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, 
Multiple-Site Clinical Study 
Sponsor 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, Hawthorne, NY 10532 
 
Protocol Number 
DSXS 1505 
 
Novum Study Number 
71542603 
 
Protocol Date 
02/15/17 
 
NIIRB 
February 21, 2017 
APPROVED 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 2 of 52 
 
 
2.0 
KEY STUDY PERSONNEL AND FACILITIES 
 
Sponsor: 
 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, Hawthorne, NY 10532 
 
 
CRO: 
 
Novum Pharmaceutical Research Services (Novum) 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
 
Sponsor’s Representative: 
 
Natalie Yantovskiy 
Senior Director, Clinical Research 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, Hawthorne, NY 10532 
Phone: 914-345-9001 Ext 6849 
Fax: 914-593-0078 
Email: Natalie.Yantovskiy@Taro.com 
 
 
CRO representative 
 
Gail Gongas 
Vice President, Clinical Trials and Data Management 
Novum Pharmaceutical Research Services 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
Tel: 412-363-3300 x 522 
Fax: 412-362-5783 
Email: gdgongas@novumprs.com 
 
 
Medical  Monitor: 
 
Paolo Maria Fanzio, MD 
Medical Monitor 
Novum Pharmaceutical Research Services 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
Tel: 412-363-3300 x597 
Fax: 412-924-0522 
Email: pfanzio@novumprs.com 
 
Biostatistician: 
 
Jianhua Liu, MSc 
Senior Biostatistician 
Novum Pharmaceutical Research Services 
Tel: 647-779-6883 
Email: jliu@novumprs.com 
 
 
 
 




CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 4 of 52 
 
 
PRINCIPAL INVESTIGATOR’S SIGNATURE 
 
 
I _______________________________________, agree to conduct protocol DSXS 1505 Rev. 5 in 
accordance with FDA regulations, ICH guidelines and Good Clinical Practice. I understand that no 
deviations from the protocol may be made without the prior permission of the Sponsor (Taro 
Pharmaceuticals, U.S.A., Inc.) or Novum Pharmaceutical Research Services, the company managing the 
study. 
 
 
 
 
 
___________________________________ 
 
 
           __________ 
Principal Investigator 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 5 of 52 
 
 
3.0 
TABLE OF CONTENTS 
 
1.0 
TITLE PAGE .................................................................................................................................... 1 
2.0 
KEY STUDY PERSONNEL AND FACILITIES ............................................................................ 2 
SIGNATURE PAGE .................................................................................................................................... 3 
3.0 
TABLE OF CONTENTS .................................................................................................................. 5 
4.0 
SYNOPSIS ........................................................................................................................................ 8 
5.0 
STUDY SCHEMATIC ................................................................................................................... 14 
6.0 
LIST OF ABBREVIATIONS AND TERMS ................................................................................. 15 
7.0 
INTRODUCTION .......................................................................................................................... 16 
7.1 
Disease Being Treated ................................................................................................................ 16 
7.2 
Availability and Efficacy of Already Approved Therapies ........................................................ 16 
7.3 
Scientific and Statistical Considerations ..................................................................................... 16 
7.4 
Justification for use of Placebo ................................................................................................... 17 
7.5 
Risks and Benefits ....................................................................................................................... 17 
8.0 
STUDY OBJECTIVE ..................................................................................................................... 18 
9.0 
INVESTIGATIONAL PLAN ......................................................................................................... 18 
9.1 
Study Design and Plan Description ............................................................................................ 18 
9.2 
Selection of Study Design ........................................................................................................... 19 
9.3 
Selection of Study Population ..................................................................................................... 20 
9.3.1 
Inclusion Criteria................................................................................................................. 20 
9.3.2 
Exclusion Criteria ............................................................................................................... 20 
9.3.3 
Restrictions during the Study .............................................................................................. 22 
9.3.4 
Removal of Patients from the Study ................................................................................... 23 
9.3.5 
Early Terminations .............................................................................................................. 23 
9.4 
Treatments ................................................................................................................................... 23 
9.4.1 
Treatments Administration ................................................................................................. 24 
9.4.2 
Identity of Investigational Product ...................................................................................... 24 
9.4.3 
Method of Assigning Patients to Treatment Groups ........................................................... 25 
9.4.4 
Study Blind ......................................................................................................................... 25 
9.4.5 
Compliance ......................................................................................................................... 26 
9.5 
Study Conduct ............................................................................................................................. 26 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 6 of 52 
 
 
9.5.1 
Visit 1 (Day 1): Randomization .......................................................................................... 26 
9.5.2 
Visit 2 (Day 7 ± 2): Interim Visit ........................................................................................ 27 
9.5.3 
Visit 3 (Day 14 ± 2): Interim Visit ...................................................................................... 28 
9.5.4 
Visit 4 (Day 28 ± 2): End of Treatment .............................................................................. 28 
9.5.5 Visit 5 (Day 42 ± 4): Follow-up Phone Call .............................................................................. 29 
9.6 
Study Procedures ........................................................................................................................ 29 
9.6.1 
Informed Consent ................................................................................................................ 29 
9.6.2 
Demographics ..................................................................................................................... 29 
9.6.3 
Medical History................................................................................................................... 29 
9.6.4 
Vital Signs ........................................................................................................................... 29 
9.6.5 
Height and Weight .............................................................................................................. 30 
9.6.6 
Concomitant Medication Use .............................................................................................. 30 
9.6.7 
Pregnancy Test .................................................................................................................... 30 
9.6.8 
Dispensing Study Medication ............................................................................................. 30 
9.6.9 
Collecting Study Drug ........................................................................................................ 30 
9.6.10 
Dosing Instructions and Diary ............................................................................................ 30 
9.6.11 
Dosing Compliance ............................................................................................................. 30 
9.6.12 
Dermatological Assessment ................................................................................................ 31 
9.6.13 
Health Status/Adverse Events ............................................................................................. 32 
9.7 
Adverse Events ........................................................................................................................... 32 
9.7.1 
Adverse Event Definitions .................................................................................................. 32 
9.7.2 
Severity of Adverse Event .................................................................................................. 32 
9.7.3 
Relationship of Adverse Event ........................................................................................... 32 
9.7.4 
Patient’s Participation Stopping Criteria ............................................................................. 33 
9.8 
Serious Adverse Events .............................................................................................................. 33 
9.8.1 
Definition of a Serious Adverse Event ................................................................................ 33 
9.8.2  
Reporting Serious Adverse Events ..................................................................................... 34 
10.0 
STATISTICAL METHODS ........................................................................................................... 35 
10.1 
Statistical Plan ............................................................................................................................. 35 
10.2 
Determination of Sample Size .................................................................................................... 35 
10.3 
Study Populations ....................................................................................................................... 35 
10.3.1 
Intent-to-Treat (ITT) Population ......................................................................................... 35 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 7 of 52 
 
 
10.3.2 
Per-Protocol (PP) Population .............................................................................................. 36 
10.3.3 
Safety Population ................................................................................................................ 36 
10.4 
Baseline Comparability ............................................................................................................... 36 
10.5 
Efficacy Endpoints ...................................................................................................................... 36 
10.6 
Primary Efficacy Analysis .......................................................................................................... 38 
10.7 
Secondary Efficacy Analysis ...................................................................................................... 38 
10.8 
Treatment-by-Site Interaction and Pooling of Clinical Sites ...................................................... 38 
10.9 
Safety Analysis ........................................................................................................................... 38 
11.0 
REGULATORY OBLIGATIONS .................................................................................................. 39 
11.1 
Institutional Review Board ......................................................................................................... 39 
11.2 
Study Documentation .................................................................................................................. 39 
11.2.1 
Protocol ............................................................................................................................... 39 
11.2.2 
Informed Consent ................................................................................................................ 39 
11.2.3 
Protocol and Informed Consent Changes ............................................................................ 40 
11.2.4 
Source Documents and Case Report Forms ........................................................................ 40 
11.2.5 
Drug Accountability ............................................................................................................ 40 
11.2.6 
Drug Storage ....................................................................................................................... 40 
11.2.7 
Pregnancies ......................................................................................................................... 40 
11.2.8 
Reporting Safety Information to the IRB ............................................................................ 41 
11.2.9 
Record Retention................................................................................................................. 41 
11.2.10 
Study Monitoring and Auditing ...................................................................................... 41 
11.2.11 
End of the Trial ............................................................................................................... 42 
11.2.12 
Clinical Study Report ...................................................................................................... 42 
12.0 
REFERENCES ............................................................................................................................... 43 
13.0 
APPENDICES ................................................................................................................................ 45 
13.1 
Appendix A ................................................................................................................................. 45 
13.2 
Appendix B ................................................................................................................................. 47 
13. 3 
Appendix C ............................................................................................................................. 48 
13.4  
Appendix D ................................................................................................................................. 49 
13.5 
Appendix E ...................................................................................................................................... 50 
13.6 
Appendix F ...................................................................................................................................... 51 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 8 of 52 
 
 
4.0 
SYNOPSIS 
 
Protocol Number 
71542603 
Title 
A 
Randomized, 
Double-Blind, 
Placebo-Controlled, 
Parallel-Design, 
Multiple-Site Clinical Study to Evaluate the Efficacy and Safety of 
Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.) 
in Patients with Mild to Moderate Plaque Psoriasis 
Objectives 
To evaluate the therapeutic efficacy and safety of desoximetasone topical 
spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.) compared to a Placebo 
(vehicle) spray (Taro Pharmaceuticals, U.S.A., Inc.) in patients with mild to 
moderate plaque psoriasis 
Sponsor 
Taro Pharmaceuticals, U.S.A., Inc. 
Study Products 
• 
Test: Desoximetasone topical spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.)  
• 
Placebo: Vehicle spray (Taro Pharmaceuticals, U.S.A., Inc.) 
Route of 
Administration 
Topical 
Treatment 
Randomization 
1:1 (Test: Placebo) 
Patient Population 
Up to 120 male and non-pregnant females, 12 years of age or older, with a 
confirmed diagnosis of mild to moderate plaque psoriasis will be enrolled to 
provide for up to 60 patients per each treatment group (Test or Placebo).  
Enrollment will begin with the 18 and older population.  Enrollment for 
patients 12-17 will begin once we have safety data from the Phase 2 study has 
be reviewed. 
Study Design 
Randomized, double-blind, placebo-controlled, multiple-site, parallel design 
Study Conduct 
Eligible patients will be randomized in a 1:1 ratio to Test or Placebo product. 
Patients will complete 4 clinic visits over a 4 week study duration as follows: 
• 
Visit 1: Randomization (Day 1), 
• 
Visit 2: Interim Visit (Day 7 ± 2), 
• 
Visit 3: Interim Visit (Day 14 ± 2), 
• 
Visit 4: End of Treatment (Day 28 ± 2). 
Patients will be contacted at Day 42 ± 4 (Visit 5) for a Telephone Follow-up 
to report any Adverse Events that have occurred since the end of treatment, 
Therapeutic efficacy evaluation will be based on clinical assessment of 
plaque psoriasis by the Investigator. Such clinical assessment will include 
scoring of the severity of signs and symptoms of plaque psoriasis. Refer to 
Appendices A, B and C for body surface area (BSA) estimation, 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 9 of 52 
 
 
Investigator’s Global Assessment Scale (IGA), Total Lesion Severity Score 
(TLSS) and Psoriasis Area Severity Index (PASI), respectively. 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female 12 years of age or older. 
2. Signed informed consent form (ICF), which meets all criteria of current. 
FDA regulations. For patients under the age of majority in the state the 
study is being conducted (18 years in most states) the parent or legal 
guardian should sign the consent form and the child will be required to 
sign a patient “assent” form that will be written in such a way as to be 
understandable to a child. 
3. If female and of child-bearing potential, prepare to abstain from sexual 
intercourse or use a reliable method of contraception during the study 
(e.g., condom + spermicide, IUD, oral, transdermal, injected or implanted 
hormonal contraceptives). 
4. Have a definite clinical diagnosis of stable plaque psoriasis involving 5-
10% of the body surface area (BSA). Refer to Appendix A. 
5. Have a plaque elevation score of ≥ 2 (mild) for the Target Lesion (based 
on TLSS, Appendix B). 
6. The Target Lesion must have an area of at least 5 cm².  
7. Have a Investigator’s Global Assessment (IGA) score of 2 (mild) or 3 
(moderate) at baseline for the overall disease severity (Appendix C). 
8. Target Lesion must not be on the face, genitals, or intertriginous area 
(i.e., breast fold, gluteal crease, axilla, etc.). 
 
Exclusion Criteria 
1. Patient is < 12 years old. 
2. Female who is pregnant, nursing, planning to become pregnant during the 
duration of the study, or if of child-bearing potential and sexually active 
and not prepared to use appropriate contraceptive methods to avoid 
pregnancy. 
3. Has less than 5%  or greater than 10% of BSA affected with plaque 
psoriasis. 
4. A score of < 2 (mild) for the individual sign of plaque elevation for the 
Target Lesion (based on TLSS, Appendix B). 
5. Target Lesion area less than 5 cm². 
6. Investigator’s Global Assessment (IGA) Score < 2 (mild) or > 3 
(moderate) at baseline for the overall disease severity.  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 10 of 52 
 
 
7. Patient has current diagnosis of other types of psoriasis other than stable 
plaque psoriasis (i.e. acute, guttate, erythrodermic, exfoliative or pustular 
psoriasis) or has psoriasis of any kind of the face or scalp that will require 
active treatment during the study. Nonprescription antipsoriatic 
shampoos will be allowed during the study when applied solely to the 
scalp. 
8. Patient presents active cutaneous bacterial or viral infection at baseline 
and/or skin atrophy in ant treatment area.  
9. Patient has a history of psoriasis that has been unresponsive to topical 
corticosteroid therapy. 
10. In the Investigator’s opinion, the patient has other dermatological 
conditions, such as atopic or contact dermatitis, that may interfere with 
the clinical assessments of the signs and symptoms of psoriasis. 
11. Patient has a history of allergy or sensitivity to corticosteroids or history 
of any drug hypersensitivity or intolerance which, in the opinion of the 
Investigator, would compromise the safety of the patient or the results of 
the study. 
12. Patient has a significant history or current evidence of chronic infectious 
disease, system disorder, organ disorder or other medical condition that, 
in the Investigator’s opinion, would place the study patient at undue risk 
by participation in the study.  
13. Patient is currently receiving or has received any radiation therapy, anti-
neoplastic agents or immunosuppressant medication within 4 weeks 
before the first dose of study drug.  
14. Patient has undergone treatment with any systemic or photo antipsoriatic 
therapy within 8 weeks of the first dose of study drug.  
15. Patient has been treated within 12 weeks (or five half lives, whichever is 
less) before the first dose of study drug with any biological therapies for 
psoriasis. 
16. Patient has received any systemic steroids within 4 weeks of the first 
dose of the study drug. The use of inhaled or intranasal corticosteroids is 
acceptable as long as usage has been stable for at least 2 weeks before the 
first dose of study drug and will be continued during the study. 
17. Females using hormonal contraceptives for less than one complete cycle 
before entering the study.  
18. Patients who have used any topical anti-psoriatic agents of any kind or 
any topical corticosteroids for any reason within 2 weeks before first use 
of study drug. Nonprescription anti-psoriatic shampoos used only on the 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 11 of 52 
 
 
scalp will be allowed during the study.  
19. Receipt of any drug as part of a research study within 30 days before first 
dosing. 
20. In the opinion of the Investigator, the patient will not be compliant with 
the requirements of the study procedures. 
21. Previous participation in this study. 
Efficacy 
Endpoints 
Primary Efficacy Endpoints 
1. The proportion of patients in each treatment group who are considered a 
Clinical Success at Day 28 ± 2 (i.e., at least a 2-grade improvement from 
the patient’s baseline IGA score) 
2. The proportion of patients in each treatment group who are considered a 
Treatment Success for the Target Lesion at Day 28 ± 2 (i.e., a TLSS 
value of 0 or 1 at Day 28 ± 2 for each of the three signs and symptoms 
(i.e., erythema, scaling and plaque elevation) depending on the patient’s 
baseline TLSS) 
Definitions: 
1. Treatment Success: To be considered a Treatment Success the patient’s 
TLSS value at Day 28 ± 2 must be 0 if their baseline TLSS value is 2 and 
must be 0 or 1 if their baseline TLSS value is > 2 for each of the 
individual signs and symptoms 
2. Treatment Failure: A patient will be considered a Treatment Failure if: 
a. the patient’s TLSS value is > 0 if their baseline TLSS value is 2 or > 
1 if their baseline IGA score is > 2 for any of the individual signs and 
symptoms 
b. the patient was considered to have an insufficient therapeutic 
response 
3. Clinical Success: To be considered a Clinical Success the patient must 
have at least a 2-grade improvement from their baseline IGA score. That 
is, an IGA score of 0 at Day 28 ± 2 if their baseline IGA score is 2 or an 
IGA score of 0 or 1 at Day 28 ± 2 if their baseline IGA score is 3 
4. Clinical Failure: A patient will be considered a Clinical Failure if: 
a. the patient’s IGA score is > 0 if the baseline IGA score is 2 or > 1 if 
the baseline IGA score is 3 
b. the patient was considered to have an insufficient therapeutic 
response 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 12 of 52 
 
 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
1. The proportion of patients with a baseline IGA score of 3 who are 
considered a Clinical Success. 
2. The proportion of patients with a baseline IGA score of 3 who are 
considered a Treatment Success. 
3. The proportion of patients with a baseline IGA score of 2 who are 
considered a Clinical Success. 
4. The proportion of patients with a baseline IGA score of 2 who are 
considered a Treatment Success. 
5. The change from baseline in %BSA affected at Day 28 ± 2 
Therapeutic 
Efficacy Analysis 
Primary Efficacy Analyses 
The Test treatment will be compared with Placebo for each primary endpoint 
at the 5% significance level (p < 0.05; two-sided, Cochran-Mantel-Haenszel 
exact test) in the intent-to-treat (ITT) population using last observation 
carried forward (LOCF). As this is a multiple-site study, the interaction of 
treatment-by-site may be evaluated by the Breslow-Day test for homogeneity 
of the odds ratio at the 5% significance level (p < 0.05) for the primary 
efficacy variable in the ITT population for superiority testing. Superiority of 
Test over Placebo will be demonstrated if both dichotomous endpoints show 
statistical significance at the 5% significance level. For sensitivity testing, the 
primary analysis will also be performed using the per protocol (PP) 
population. 
Secondary Efficacy Analyses 
The Test treatment will be compared with Placebo for each dichotomous 
secondary endpoint at the 5% significance level (p < 0.05; two-sided, 
Cochran-Mantel-Haenszel exact test) in the ITT population using LOCF.  
The Test treatment will be compared with Placebo for the continuous 
secondary endpoint at the 5% significance level in the ITT population using 
last observation carried forward (LOCF). Analysis of Covariance 
(ANCOVA) will be used for the evaluation of the continuous secondary 
endpoint using baseline %BSA as a covariate. 
For the secondary efficacy analyses, superiority of Test over Placebo will be 
considered supported for each endpoint if the difference is statistically 
significantly greater than 0 at the 5% significance level. There will be no 
multiplicity adjustment for the evaluation of the five secondary endpoints. 
Descriptive statistical analysis will be generated to compare the efficacy 
results in each treatment group at each visit. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 13 of 52 
 
 
Safety Analysis 
Adverse events (AEs) will be classified using standard MedDRA terminology 
Version 17.0 or higher and summarized by treatment group. Summary tables 
comparing the type, incidence, severity will be prepared by treatment group. 
The relationship of AEs, if any, to the study drug will be assessed by the 
Investigator.  All AEs will be presented regardless of suspected causality.  
The frequency, severity and relationship to study drug for AEs in each 
treatment group will be used to evaluate the safety profile of the test product. 
Sample Size 
Determination 
The primary analyses of interest are the proportion of patients in the Test and 
Vehicle treatment groups who are considered to be a Clinical Success and 
Treatment Success on Day 28.  
In-house data from two Phase III studies that evaluated the safety and efficacy 
of desoximetasone spray 0.25% (twice daily for 28 days) in patients with 
moderate to severe plaque psoriasis were used for sample size determination. 
These studies were conducted in support of Taro’s NDA #204141, Topicort® 
(desoximetasone) Topical Spray, 0.25%. In those studies the Clinical Success 
rates were 31% and 53% for the active product (42% average) and 5% and 
18% for the vehicle treatment (12% average), and the Treatment Success rates 
were 39% and 53% for the active product (46% average) and 7% and 17% for 
the vehicle treatment (12% average). 
Based on the average results from these two studies on the 0.25% spray, the 
proportion of subjects in the Test group considered a Clinical Success and 
Treatment Success is expected be 40% or higher and the proportion of subjects 
in the Vehicle group considered a Clinical Success and Treatment Success is 
expected to be 12% or less for desoximetasone spray 0.15% in patients with 
mild to moderate plaque psoriasis. With these assumptions, 50 evaluable 
subjects in the ITT in each treatment group will demonstrate superiority of the 
Test to the Vehicle group with 89% power at the 5% level of significance (p < 
0.05, using two-sided Z-test), assuming 100% correlation between Clinical and 
Treatment Success rates. 
To allow for patients who may drop out from the study or are otherwise non-
evaluable, up to 120 patients may be enrolled (60 in the Test group and 60 in 
the Vehicle group). 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 14 of 52 
 
 
5.0 
STUDY SCHEMATIC 
* Pregnancy Test will be conducted for women of child-bearing potential 
** Selected sites will be designated to take photographs of a defined target lesion at each Clinic 
Visit 
 
PROCEDURE 
VISIT 1 
Randomization 
Day 1 
 
VISIT 2 
Interim Visit 
Day 7   
± 2 days 
VISIT 3 
Interim Visit 
Day 14   
± 2 days 
VISIT 4 
End of 
Treatment 
Day 28   
± 2 days 
 
VISIT 5 
Telephone 
Follow-Up 
Visit 
Day 42  
± 4 days 
Informed Consent 
X 
 
 
 
 
Medical History & 
Demographics 
X 
 
 
 
 
Height and Weight 
X 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
 
Dermatological 
Assessment 
X 
X 
X 
X 
 
% BSA Assessment 
X 
X 
X 
X 
 
IGA Score 
X 
X 
X 
X 
 
Total Lesion Severity 
Score 
X 
X 
X 
X 
 
PASI Score 
X 
X 
X 
X 
 
Application Site 
Reactions 
X 
X 
X 
X 
 
Target Lesion 
Photograph** 
X 
X 
X 
X 
 
Pregnancy Test* 
X 
 
 
X 
 
Concomitant 
Medication 
X 
X 
X 
X 
 
Collect/Dispense Study 
Medication 
X 
 
X 
X 
 
Provide/Review patient 
Dosing Diary 
X 
X 
X 
X 
 
Adverse Events 
 
X 
X 
X 
X 
Evaluation of Patient 
Compliance to the 
Protocol 
 
X 
X 
X 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 15 of 52 
 
 
6.0 
LIST OF ABBREVIATIONS AND TERMS 
 
 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
C 
Celsius 
CRF  
Case Report Form 
CRO  
Clinical Research Organization 
eCTD 
electronic Common Technical Document 
FDA  
Food and Drug Administration 
HPA  
Hypothalamic Pituitary Adrenal 
HRT  
Hormone Replacement Therapy 
ICF  
Informed Consent Form 
ICH 
International Conference on Harmonization 
IGA 
Investigator’s Global Assessment 
IND 
Investigational New Drug  
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD  
Intrauterine Device 
LOCF 
Last Observation Carried Forward 
ml 
milliliter 
NDA  
New Drug Application 
OHRP 
Office of Human Rights Protection 
OTC 
Over The Counter 
PASI 
Psoriasis Area Severity Index 
PP 
Per-Protocol 
SAE  
Serious Adverse Event 
TLSS 
Total Lesion Severity Score 
U.S.A.  
United States of America 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 16 of 52 
 
 
7.0 
INTRODUCTION 
7.1 
Disease Being Treated 
Psoriasis is an immune (T-cell)-mediated inflammatory skin disease that affects 
approximately 2% of the western population.1 The most common type of psoriasis in both 
adults and children is plaque psoriasis, which is characterized by the presence of raised, 
thickened red lesions that are covered by silvery white scales, most commonly seen on 
the knees and/or elbows. Although there are reports implicating a genetic association 
with the disease, there are also studies that have established a set of psoriasis triggers 
including stress, medications (such as lithium, antimalarials, indomethacin, quinidine, 
beta blockers), injury or infection. The condition is considered chronic although the 
frequency and severity of outbreak in an individual can fluctuate without apparent 
cause.1-3 
Psoriasis severity is determined using various tools, the most extensively studied index  
being the Psoriasis Area and Severity Index (PASI), which is a measure of the average 
redness, thickness, and scaliness of the lesions (each graded on a 0–4 scale), weighted by 
the % body surface area of involvement.4,5 Investigator’s Global Assessment (IGA) is 
also one of the preferred methods of clinical evaluation of the severity and extent of 
psoriasis. 2,4,5  
7.2 
Availability and Efficacy of Already Approved Therapies 
Treatment of  plaque  psoriasis  depends  on  the  severity  of  the  condition,  previous 
treatment regimens and personal preference of the patient. Psoriasis treatments 
historically include topical creams, sprays, lotions, foams. Examples of marketed 
products include corticosteroids (Topicort®, Clobex™), Vitamin A & D derivatives 
(Tzorac®, Dovonex®), NSAIDs (salicylic acid), etc. For more severe cases, systemic 
therapy (methotrexate, oral retinoids, UV light, biologics etc) may be warranted; 
however, the side effect profile of these products limits their use. 2,6,7  
Desoximetasone is a high potency synthetic corticosteroid marketed in a number of 
formulations:  gel (0.05%), cream (0.05% and 0.25%), and ointment (0.05% and 0.25%). 
All these formulations are encompassed under the Topicort® brand, acquired by Taro 
Pharmaceuticals U.S.A., Inc. (Taro) in 2004.  Most recently, Taro received approval on 
April 11, 2013 for a new dosage form (spray) under NDA #204141, Topicort® 
(desoximetasone) Topical Spray, 0.25%, a super high potency formulation that is 
indicated for the treatment of plaque psoriasis in patients 18 years of age or older. 
A new formulation; desoximetasone topical spray, 0.15% has been developed by Taro 
Pharmaceuticals U.S.A., Inc., and is the Test product used in this study. 
7.3 
Scientific and Statistical Considerations 
Taro Pharmaceuticals USA, Inc. has developed and marketed Topicort ® (desoximetasone 
0.25%) topical spray, and Topicort ® (desoximetasone 0.25% & 0.05%) topical creams, 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 17 of 52 
 
 
for the treatment of plaque psoriasis.8 Topical  application  of  high  potency  steroids  at  
the  recommended  dosing  levels  are usually well tolerated in all populations, with less 
than 2% of patients reporting adverse reactions (7% in the pediatric population). The 
most commonly reported adverse events are burning, stinging, pruritus, and skin 
thinning/atrophy.1,2,6,7,9 
The design for this study is based on results from Phase II dose-ranging and Phase III 
efficacy studies (NDA # 204141) conducted for Topicort® (desoximetasone) 0.25% 
topical spray (Taro Pharmaceuticals U.S.A., Inc.).10,11 The primary efficacy endpoints 
(Clinical Success and Treatment Success) are based on these studies as well as those 
reported in the NDA (# 021835) for the marketed product, Clobex® (clobetasol) 0.05% 
spray.12A sample size estimation of 120 enrolled patients (60 patients per treatment 
group, 1:1 ratio) is based on the assumption that ≥ 40% of patients receiving Test (active) 
treatment, and ≤ 12% of patients receiving Placebo (vehicle) treatment will have Clinical 
Success and Treatment Success.  
Statistical analyses of the clinical data will be based on FDA guidances and any 
communications with FDA on how they would like such data analyzed.  
7.4 
Justification for use of Placebo 
Based on recommendations from FDA, ICH and the guidebook to Institutional Review 
Boards (IRBs) issued by the Office of Human Rights Protection (OHRP), a Division of 
the United States Federal Government’s Department of Health and Human Services, a 
Placebo group will be included to confirm the sensitivity of the clinical endpoint and to 
demonstrate that the Test product is therapeutically superior to a vehicle formulation 
containing no active ingredient to treat plaque psoriasis.13,14 
7.5 
Risks and Benefits 
According to recommendations from the IRB guidebook referenced above, the risks and 
benefits to patients enrolled in clinical research studies that include a placebo treatment 
group must be carefully considered based on three main criteria, namely: the disease 
being treated, the availability, efficacy and safety of approved therapies and the scientific 
and statistical requirements of the desired outcome of the research study. Qualified 
patients entering the active treatment period have a 50% chance of receiving Placebo. 
Although the potential for any drug-related side effects of significance occurring during 
the study are low, the risk is higher in the active treatment group than in the Placebo 
group.  
All patients enrolled in this study will receive the benefit of free specialized medical care 
beyond standard medical treatment that would be expected through most health insurance 
plans. In addition, the patient will receive a stipend for participation to cover costs and 
expenses associated with trips to the medical facility. 
 
Desoximetasone is a high potency synthetic corticosteroid marketed in a number of 
formulations:  gel (0.05%), cream (0.05% and 0.25%), ointment (0.05% and 0.25%) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 18 of 52 
 
 
indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-
responsive dermatoses in patients 18 years and older.  In 2013 a new dosage form (spray) 
received the FDA approval under NDA #204141, Topicort® (desoximetasone) Topical 
Spray, 0.25%, a super high potency formulation that  is indicated for the treatment of 
plaque psoriasis in patients 18 years of age and older.  The new product does not pose a 
safety concern in patients 18 years and older because the concentration of 
desoximetasone in the new formulation of desoximetasone spray 0.15% does not exceed 
concentrations of the marketed products. The study enrollment will be initiated for 
patients 18 years of age and older. The enrollment for younger patients will be open after 
completion of the corresponding age cohort in the safety study to assess the potential for 
adrenal suppression following maximal use treatment. 
 
8.0 
STUDY OBJECTIVE 
To evaluate the therapeutic efficacy and safety of desoximetasone topical spray, 0.15% (Taro 
Pharmaceuticals, U.S.A., Inc.) compared to a Placebo (vehicle) spray (Taro Pharmaceuticals, 
U.S.A., Inc.) in patients with mild to moderate plaque psoriasis. 
 
9.0 
INVESTIGATIONAL PLAN 
9.1 
Study Design and Plan Description 
This double-blind, randomized, placebo-controlled, parallel group, multi-site study is 
designed to evaluate the therapeutic efficacy and safety of desoximetasone topical spray, 
0.15% (Taro Pharmaceuticals, U.S.A., Inc.). 
Up to 120 patients will be enrolled to randomize up to 60 patients in the Test group and 60 
in the Placebo group. Before any study-specific procedures are performed all patients will 
read and sign the IRB-approved informed consent form. In addition, patients considered 
as minors by the state law in which the clinical site is located (in most States under 18 
years of age), must have a signed parental/guardian Informed Consent Form (ICF), 
indicating approval to participate, as well as a signed assent to participate form. 
To qualify for inclusion in the study, patients must be at least 12 years of age with a 
confirmed diagnosis of mild to moderate plaque psoriasis and must fulfill the following 
primary inclusion criteria: 
• 
An affected BSA of 5 - 10% (Appendix A) 
• 
A IGA score of 2 (mild) or 3 (moderate) (Appendix B) 
• 
Target Lesion area of at least 5 cm² 
• 
Plaque Elevation Score ≥ 2 for the Target Lesion (based on TLSS score, 
Appendix B) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 19 of 52 
 
 
At Visit 1, patients who meet all inclusion/exclusion criteria will be randomized in a 1:1 
ratio (Test: Placebo) for 28 days of treatment: 
• 
Test: Desoximetasone topical spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.)  
• 
Placebo: Vehicle spray (Taro Pharmaceuticals, U.S.A., Inc.) 
Randomized study medication will be self-administered by the patient for 28 days. 
Patients will be instructed to spray the study medication directly to all affected areas and 
gently and completely rub in the study drug twice a day for 28 days. Study medication 
will be applied in the morning and evening approximately 12 hours apart. Patients will 
return to the clinic at scheduled Visits 2, 3 and 4.  Each patient will be provided with a 
dosing diary in which they will be required to record dosing dates and times. These 
diaries should be brought to each visit so that the study staff may check compliance. At 
the end of the study, the dosing diaries will be retained in the patient’s file as source 
documentation. 
During the study patients will visit the research center for a total of 4 scheduled visits: 
• 
Visit 1: Randomization (Day 1), 
• 
Visit 2: Interim Visit (Day 7 ± 2), 
• 
Visit 3: Interim Visit (Day 14 ± 2), 
• 
Visit 4: End of Treatment (Day 28 ± 2). 
Patients will be contacted at Day 42 ± 4 (Visit 5) for a Telephone Follow-up to report any 
Adverse Events that have occurred since the end of treatment, 
 
Evaluation of therapeutic efficacy will be primarily based on dermatological evaluation 
of psoriasis. The evaluation will include scoring of the extent and severity of plaque 
psoriasis. Refer to Appendices A, B and C for body surface area (BSA) estimation, 
Investigator’s Global Assessment Scale (IGA), Total Lesion Severity Score (TLSS) and 
Psorasis Area Score Index (PASI), respectively.  Selected sites will be instructed to take 
photographs of a target lesion at each visit. 
9.2 
Selection of Study Design 
The study design is primarily based on Phase III efficacy studies (NDA#204141) 
conducted for Topicort® (desoximetasone) 0.25% topical spray (Taro Pharmaceuticals 
U.S.A., Inc.) and communications between Taro Pharmaceuticals, U.S.A., Inc. and the 
FDA regarding the scope and design of clinical studies for desoximetasone topical spray, 
0.15%.  The study also follows recommendations provided in the FDA guidance 
document for topical dermatological products, and information available from published 
clinical trials in plaque psoriasis.4,7,10,11,13,15 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 20 of 52 
 
 
9.3 
Selection of Study Population 
9.3.1 
Inclusion Criteria 
1. Male or non-pregnant, non-lactating female 12 years of age or older. 
2. Signed informed consent form (ICF), which meets all criteria of current FDA 
regulations. For patients under the age of majority in the state the study is 
being conducted (18 years in most states) the parent or legal guardian should 
sign the consent form and the child will be required to sign a patient “assent” 
form that will be written in such a way as to be understandable to a child. 
3. If female and of child-bearing potential, prepare to abstain from sexual 
intercourse or use a reliable method of contraception during the study (e.g., 
condom + spermicide, IUD, oral, transdermal, injected or implanted 
hormonal contraceptives). 
4. Have a definite clinical diagnosis of stable plaque psoriasis involving 5-10% 
of the body surface area (BSA). Refer to Appendix A. 
5. Have a plaque elevation score of ≥ 2 (mild) for the Target Lesion (based on 
TLSS score, Appendix B). 
6. The Target Lesion must have an area of at least 5 cm².  
7. Have a Investigator’s Global Assessment (IGA) score of 2 (mild) or 3 
(moderate) at baseline for the overall disease severity (Appendix C). 
8. Target Lesion must not be on the face, genitals, or intertriginous area (i.e., 
breast fold, gluteal crease, axilla, etc.). 
9.3.2 
Exclusion Criteria 
1. Patient is < 12 years old. 
2. Female who is pregnant, nursing, planning to become pregnant during the 
duration of the study, or if of child-bearing potential and sexually active and 
not prepared to use appropriate contraceptive methods to avoid pregnancy. 
3. Has less than 5% or greater than 10% of BSA affected with plaque psoriasis. 
4. A score of < 2 (mild) for the individual sign of plaque elevation for the 
Target Lesion at screening. 
5. Target Lesion area less than 5 cm² at screening. 
6. Investigator’s Global Assessment (IGA) Score < 2 (mild) or > 3 (moderate) 
at screening for the overall disease severity.  
7. Patient has current diagnosis of other types of psoriasis other than stable 
plaque psoriasis (i.e., acute, guttate, erythrodermic, exfoliative or pustular 
psoriasis) or has psoriasis of any kind of the face or scalp that will require 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 21 of 52 
 
 
active treatment during the study. Nonprescription antipsoriatic shampoos 
will be allowed during the study when applied solely to the scalp. 
8. Patient presents active cutaneous bacterial or viral infection at baseline 
and/or skin atrophy in ant treatment area.  
9. Patient has a history of psoriasis that has been unresponsive to topical 
corticosteroid therapy. 
10. In the Investigator’s opinion, the patient has other dermatological conditions, 
such as atopic or contact dermatitis, that may interfere with the clinical 
assessments of the signs and symptoms of psoriasis. 
11. Patient has a history of allergy or sensitivity to corticosteroids or history of 
any drug hypersensitivity or intolerance which, in the opinion of the 
Investigator, would compromise the safety of the patient or the results of the 
study. 
12. Patient has a significant history or current evidence of chronic infectious 
disease, system disorder, organ disorder or other medical condition that, in 
the Investigator’s opinion, would place the study patient at undue risk by 
participation in the study.  
13. Patient is currently receiving or has received any radiation therapy, anti-
neoplastic agents or immunosuppressant medication within 4 weeks before 
the first dose of study drug.  
14. Patient has undergone treatment with any systemic or photo antipsoriatic 
therapy within 8 weeks of the first dose of study drug.  
15. Patient has been treated within 12 weeks (or five half lives, whichever is 
less) before the first dose of study drug with any biological therapies for 
psoriasis. 
16. Patient has received any systemic steroids within 4 weeks of the first dose of 
the study drug. The use of inhaled or intranasal corticosteroids is acceptable 
as long as usage has been stable for at least 2 weeks before the first dose of 
study drug and will be continued during the study. 
17. Females using hormonal contraceptives for less than one complete cycle 
before entering the study.  
18. Patients who have used any topical anti-psoriatic agents of any kind or any 
topical corticosteroids for any reason within 2 weeks before first use of study 
drug. Nonprescription anti-psoriatic shampoos used only on the scalp will be 
allowed during the study.  
19. Receipt of any drug as part of a research study within 30 days before first 
dosing. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 22 of 52 
 
 
20. In the opinion of the Investigator, the patient will not be compliant with the 
requirements of the study procedures. 
21. Previous participation in this study. 
9.3.3 
Restrictions during the Study 
The following concomitant medications will not be allowed while enrolled in the 
study: 
• 
Any prescription or OTC topical, systemic, phototherapy or biological 
medications or treatments for psoriasis.  
• 
Application of any emollient on the treatment area. 
• 
Any non-steroidal immunosuppressants (by any route of administration). 
• 
Use of non-sedating anti-histamines. 
o The use of sedating anti-histamines, such as diphenhydramine, 
may be acceptable on condition the patient has been on a stable 
dose for at least 14 days before enrollment and will remain on a 
stable dose throughout the study.  
• 
Any oral, topical or injectable steroid drug use (with the exception of 
HRT and contraceptives). 
o Female patients using hormonal contraceptives or HRT should 
have been on the same product/dosing regimen for at least 4 
weeks before and should not change this during the study.  
• 
New regimens of inhaled corticosteroids. 
o Inhaled or intranasal corticosteroids are permissible, provided 
that the patient has been on a stable regimen for at least 2 weeks 
before the first dose of study drug and will continue during the 
study. 
• 
Any other treatments, prescription or over-the-counter products for the 
treatment of any other dermatological condition including; topical 
corticosteroids, antibacterial, medicated and/or astringent washes, soaps, 
pads or moisturizers during the study.  
• 
Use of high strength (20% or above) alpha-hydroxy acid or any kind of 
peel or other procedures on the treatment areas (laser hair removal) 
during the study. 
Patients will be advised to avoid environmental conditions that may exacerbate 
their disease state. Patients will be advised to avoid exposure to sunlight of a 
duration that would require application of sunscreen. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 23 of 52 
 
 
Patients will be advised not to cover the skin being treated with bandages, 
dressings or wraps that will occlude the treatment area.  
Patients will be questioned about all concomitant prescription and OTC 
medication use at each study visit. All concomitant medications will be recorded 
in the patient’s study chart. Any patient who violates any of the listed restrictions 
may be dropped from continued participation in the study by the Investigator. 
9.3.4 
Removal of Patients from the Study 
Patients will be advised that they are free to withdraw from the study at any time 
for any reason, or, if necessary, the Investigator may withdraw a patient from the 
study to protect the health of that patient. A patient may also be withdrawn for 
not complying with study procedures. The clinical report will include all reasons 
for early withdrawals. 
Reasons for removal may include the following: 
• 
Worsening signs/symptoms. 
• 
Development of an intercurrent condition or complication that could affect 
the safety of the patient or the validity of evaluation of the patient’s clinical 
state to an extent considered significant by the Investigator. 
• 
Non-compliance with protocol.  
• 
Signs and symptoms of possible hypothalamus-pituitary axis (HPA) axis 
suppression. 
• 
Pregnancy. 
Patients who withdraw or are removed from the study will not be replaced.  
9.3.5 
Early Terminations  
If a patient terminates from the study early, all efforts will be made to complete 
Visit 4 study procedures. In case of early termination the Investigator shall fully 
document the reason for early termination.  
Patients who discontinue early or who significantly deviate from the protocol 
will be included in the intent-to-treat (ITT) population with LOCF. 
9.4 
Treatments 
The following treatments will be used in the study: 
• 
Test: Desoximetasone topical spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.), 
applied twice a day for 28 days 
• 
Placebo: Vehicle spray (Taro Pharmaceuticals, U.S.A., Inc.) applied twice a day 
for 28 days 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 24 of 52 
 
 
9.4.1 
Treatments Administration 
An Independent Dispenser will dispense the study medication and provide instruction on 
the dosing technique. The patient will be told to spray and gently rub in the study drug 
(until it is completely absorbed into the skin) to the affected areas twice a day (morning 
and evening), approximately 12 hours apart, for 28 days. To ensure compliance with the 
dosing technique, patients will be instructed to apply the medication under the 
supervision of the Independent Dispenser at the time of enrollment and then twice daily 
until their next scheduled visit. Patients will be provided with a dosing diary in which 
they will be required to record dosing dates and times. These diaries should be brought to 
each visit in order that the study staff may check compliance. At the end of the study, the 
dosing diaries will be retained in the patient’s file as source documentation. 
Qualified study patients will be provided with one 100 ml bottle of study medication at 
Visit 1 along with instructions for dosing. Bottles of study drug should be weighed before 
dispensing and after they are returned so the weight will be recorded.  At Visit 3 (Day 14 
± 2) the first bottle should be collected and new 100 ml bottle of spray should be 
dispensed along with dosing instructions. This bottle will be returned at Visit 4 (Day 28 ± 
2). Based on a maximum of 2 x 3 ml applications/day, 2 x 100 ml bottles of spray should 
provide sufficient drug for the study.  Bottles will be weighed at the time of dispensing 
and when returned to determine that amount of drug used.   
The patient will be informed to avoid smoking and proximity to heat or flame while using 
the product owing to the flammability of the product. 
Treatment compliance will be encouraged by instructing the patient on the proper dosing 
technique and by the use of the daily diary. Compliance will be assessed by evaluation of 
the diary and overall exposure to study drug will be assessed by weighing the study drug 
bottles before and after use (see sections 9.4.5 and 9.6.11). 
9.4.2 
Identity of Investigational Product 
 
The following products will be used in the study: 
• 
Test: Desoximetasone topical spray, 0.15% (Taro Pharmaceuticals, U.S.A., Inc.)  
• 
Placebo: Vehicle spray (Taro Pharmaceuticals, U.S.A., Inc.) 
Study products will be supplied as 2 x 100 ml bottles of spray. 
All randomized study medication will be blinded and packaged in blinded sealed boxes.  
Study medication and placebo will be packaged in identical, opaque bottles to maintain 
the study blind.  Each bottle will be identified only by a label bearing the Sponsor name, 
protocol number, randomization number, treatment duration and a statement that the 
study medication is for Investigational Use Only. The study staff will dispense the study 
medication bottle only to those patients identified by the Investigator. The study staff will 
instruct the patients on the use and return of study drug. The patient will be instructed not 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 25 of 52 
 
 
to discuss the appearance of the study medication bottle with any study personnel 
conducting the study visits i.e., the Investigator(s) or the Study Coordinator(s). 
Individual boxes containing tubes of study medication will be packaged in blocks. One 
block will consist of 4 patients’ worth of study medication (i.e., 2 x Test: 2 Placebo). The 
study medication will be shipped to each Investigator’s site from a centralized pharmacy. 
The Principal Investigator at each site is responsible for ensuring that all study 
medications are stored in a locked, secure location, with access limited to the Investigator 
and his/her designee(s). An accurate inventory of the study medication will be maintained 
in accordance with federal regulations. Study medication will be stored at controlled 
room temperature 15-30°C (59-86ºF).  
Once the site has been notified that they may do so, all unused study medication and 
empty or partially used bottles of study medication may be returned to the Sponsor or 
designee.  
9.4.3 
Method of Assigning Patients to Treatment Groups 
The study drug will be randomized, packaged and blinded by an independent 
packaging company. Randomization will be pre-planned according to a 
computer-generated randomization schedule. The randomization will be 
generated in blocks, each containing 4 patients’ worth of medication (2 x Test 
product and 2 x Placebo). Each patient kit will contain 2 x 100 ml bottles of 
study medication. 
The randomization number will be a unique 4 digit number. 
A perforated or two-part label will be attached to the box of drug supplies for 
each patient. Both pieces of the label should include the following information: 
protocol number, randomization number, space for patient’s initials, statement 
that the drug is for Investigational Use Only, space for dispensing date, storage 
information and the Sponsor’s name. One part of the label shall remain attached 
to the box. The other part will be removed before dispensing and attached to the 
patient’s source documents.  
At the end of the study, after all the clinical data have been entered and the study 
database has been locked, a copy of the randomization will be sent to the 
statistician. 
9.4.4 
Study Blind 
The Investigator, staff at the study site, study monitors, and data 
analysis/management personnel will be blinded to the patient assignment. To 
maintain the Investigator-Blind, the Independent Dispenser will be responsible 
for dispensing and collecting study medication.  The patient will be requested not 
to discuss the appearance of the study medication with the Investigator or study 
staff.  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
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Each study site will have at least one Independent Dispenser. The role of the 
Independent Dispenser is to dispense and collect all study medication from the 
patients and to ensure the study medication logs are completed. They should not 
be involved in collecting any efficacy data in the study thus ensuring the integrity 
of the study blind.  
To ensure information that could potentially bias handling of data is not 
disclosed, the clinical packaging company will hold the randomization scheme 
until database lock. For each patient an individual code break card describing the 
actual treatment will be provided with the study medication, to be unblinded only 
in the case of medical emergency and should be kept at the site with the study 
documents when the study is completed. Whenever possible, the Novum Medical 
Monitor must be contacted before breaking the blind for any patient. The code 
break cards should be stored in a secure location at all times and maintained at 
the site for all randomized patients after the completion of the study. 
At the conclusion of the study, after the database has been locked, each site will 
be sent an envelope containing the full study randomization scheme that should 
be retained with the study documents in case needed during an FDA Inspection. 
9.4.5 
Compliance 
Patients will be provided with a diary to record the time and date of dosing, other 
concomitant medications and adverse events.  Patients taking fewer than 75% or 
more than 125% of the required doses, or who missed scheduled applications for 
> 3 consecutive days will be considered non-compliant with dosing. Compliance 
with dosing will be verified by the use of the patient diaries. 
 
9.5 
Study Conduct 
9.5.1 
Visit 1 (Day 1): Randomization 
1. Informed Consent/Assent: Patients who are willing to comply with study procedures 
will read and sign the informed consent/assent. Patients under the age of majority will 
read and sign the assent to participate form and their parent or legal guardian must sign 
the consent form. 
2. Medical History: Review the patient’s demographic and medical history. 
3. Height/Weight and Vital Signs: The patient’s height (meters) and weight (kg) will be 
measured. The patient’s vital signs will be recorded (pulse, blood pressure, temperature 
and respiration rate). 
4. Dermatological Assessment: Clinical signs and symptoms of psoriasis will be evaluated 
by the Investigator based on the following: 
• 
% BSA assessment (Appendix A) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 27 of 52 
 
 
• 
IGA Score (Appendix C) 
• 
TLSS Score (Appendix B) 
• 
PASI Score (Appendix D) 
• 
Application Site Reactions (Appendix E) 
5. Pregnancy Test: A pregnancy test will be required of all female patients of childbearing 
potential before enrollment. 
6. Concomitant Medication: Review the patient’s use of concomitant medication within 
the last 12 weeks. 
7. Inclusion/Exclusion Criteria: Confirm that the patient meets all inclusion/exclusion 
criteria. 
8. Dispense Study Product: The Independent Dispenser will weigh and dispense one bottle 
of study drug to eligible patient with instructions. The first dose of study medication 
should be administered at the site, under supervision, during this visit.  
9. Provide Dosing Diary: Provide Diary with instructions for dosing and completing the 
diary. 
10. Schedule Visit 2. 
9.5.2 
Visit 2 (Day 7 ± 2): Interim Visit 
1. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature 
and respiration rate). 
2. Dermatological Assessment: Clinical signs and symptoms of psoriasis will be evaluated 
by the Investigator based on the following: 
• 
% BSA assessment (Appendix A) 
• 
IGA Score (Appendix C) 
• 
TLSS Score (Appendix B) 
• 
PASI Score (Appendix D) 
• 
Application Site Reactions (Appendix E) 
3. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since Visit 1. 
4. Adverse Events: Review and report any AEs since Visit 1. 
5. Diary Review: Collect and review patient’s dosing diary for compliance and provide new 
diary. 
6. Schedule Visit 3. 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
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9.5.3 
Visit 3 (Day 14 ± 2): Interim Visit 
1. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature 
and respiration rate). 
2. Dermatological Assessment: Clinical signs and symptoms of psoriasis will be evaluated 
by the Investigator based on the following: 
• 
% BSA assessment (Appendix A) 
• 
IGA Score (Appendix C) 
• 
TLSS Score (Appendix B) 
• 
PASI Score (Appendix D) 
• 
Application Site Reactions (Appendix E) 
3. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since Visit 2. 
4. Adverse Events: Review and report any AEs since Visit 2. 
5. Collect Study Product: The first bottle of study product will be collected and weighed. 
6. Diary Review: Collect and review patient’s dosing diary for compliance and provide new 
diary. 
7. Dispense Study Product: Independent Dispenser will weigh and dispense a new bottle 
of study product corresponding to the patient’s randomization number. 
8. Schedule Visit 4. 
 
9.5.4 
Visit 4 (Day 28 ± 2): End of Treatment 
1. Vital Signs: The patient’s vital signs will be recorded (pulse, blood pressure, temperature 
and respiration rate). 
2. Dermatological Assessment: Clinical signs and symptoms of psoriasis will be evaluated 
by the Investigator based on the following: 
• 
% BSA assessment (Appendix A) 
• 
IGA Score (Appendix C) 
• 
TLSS Score (Appendix B) 
• 
PASI Score (Appendix D) 
• 
Application Site Reactions (Appendix E) 
3. Pregnancy Test: A pregnancy test will be required of all female patients of childbearing 
potential at the last study visit. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
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4. Concomitant Medication: Review the patient’s use of any new or ongoing concomitant 
medications since Visit 3. 
5. Adverse Events: Review and report any AEs since Visit 3. 
6. Evaluation of Patient Compliance to the Protocol: Independent dispenser will collect 
and review patient’s dosing diary and record total number of doses administered since 
Visit 3. 
7. Collect Study Product: The second bottle of study product will be collected and 
weighed. 
8. Diary Review: Collect and review patient’s dosing diary for compliance. 
9. Discharge: Review completeness of all source documents for patient and discharge from 
the study. 
9.5.5 Visit 5 (Day 42 ± 4): Follow-up Phone Call 
A phone call will be conducted approximately 14 days after the subject has completed dosing to 
follow-up on any new adverse events that may have occurred. 
9.6 
Study Procedures 
9.6.1 
Informed Consent 
At Visit 1, before performing any study-related procedures the study patient must sign the 
IRB-approved consent form. If the patient is under the age of majority in the state that the 
study is being conducted (18 years in most states) then patient’s parent or legal guardian 
must sign the consent form and the patient must sign the assent form. Both the consent 
and assent forms will be reviewed and approved by an Institutional Review Board before 
study commencement. No patient will be entered into the study without reading, 
understanding, and signing an informed consent/assent. For illiterate patients, verbal 
consent should be obtained in the presence of and be countersigned by a literate witness. 
If any other language is required, translation will be performed by a certified translator. 
9.6.2 
Demographics 
At Visit 1, each patient shall be required to provide basic demographic information: date 
of birth, gender, ethnicity and race.  
9.6.3 
Medical History 
At Visit 1 patients will be questioned about personal medical history including psoriasis 
history and all medication use within the previous 12 weeks. 
9.6.4 
Vital Signs 
The patient’s vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate) at all clinic visits. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 30 of 52 
 
 
9.6.5 
Height and Weight 
At Visit 1 the subject’s body weight (kg) and height (cm) will also be measured while the 
Subject is lightly clothed (e.g., no coat or shoes). The patient’s BSA will be calculated 
using instructions in Appendix A.  
9.6.6 
Concomitant Medication Use 
At each clinic visit, patients will be questioned about current and concomitant medication 
use. Patients will also be questioned about ongoing or new concomitant medication use 
during the treatment period at Visits 2, 3 and 4. 
9.6.7 
Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed at Visits 
1 and 4. The test must be negative at Visit 1 for the patient to be eligible for inclusion in 
the study. If the patient is female and not considered of childbearing potential, then the 
reason must be documented in the patient’s source documents. 
Any patient who becomes pregnant during the study should be discontinued and end of 
treatment procedures (Visit 4) completed. The outcome of the pregnancy should be 
followed by the Investigator to the conclusion of the pregnancy. 
9.6.8 
Dispensing Study Medication 
An Independent Dispenser will dispense study medication at Visit 1, along with dosing 
instructions. Patients will be instructed to apply the first dose of study medication in the 
clinic, and the remaining doses at home. The Independent Dispenser will ensure the study 
medication logs are reported correctly.   
9.6.9 
Collecting Study Drug 
Bottles of study product will be collected at Visit 3 and Visit 4 and checked for 
compliance or evidence of tampering with the blind. 
9.6.10 Dosing Instructions and Diary 
Patients will be provided with a dosing diary at Visits 1, 2 and 3 along with instructions 
on how to complete the diary. Patients will be asked to record the time and date of each 
dose, AEs, and concomitant medications throughout the study. The diary will be 
reviewed at each visit by the study staff.  
9.6.11 Dosing Compliance 
Dosing compliance will be checked by site staff at Visits 2, 3 and 4 by reviewing patient 
diary entries.  Patients will be considered compliant with dosing if they administer 75%-
125% of the required number of doses, and did not miss more than 3 consecutive days of 
dosing.   


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 31 of 52 
 
 
9.6.12 Dermatological Assessment 
At Visit 1 a visual inspection to confirm a diagnosis of chronic plaque psoriasis will be 
performed. At each visit psoriasis will be assessed according to the following measures: 
a) % BSA Assessment: Appendix A 
b) IGA Score: Appendix C 
c) TLSS: Appendix B 
d) PASI Score:  Appendix D 
e) Application Site Reactions: Appendix E 
Wherever possible, the same Investigator should attempt to perform all IGA exams at all 
visits for an individual patient.  
During the overall dermatological assessment at Visit 1, the Investigator will determine 
which lesion in his opinion (considering a combination of size and severity of lesional 
signs and symptoms) is the most severe. This lesion must have an area of at least 5 cm² 
and have a plaque elevation score of at least 2 (mild).  
This lesion will be designated the Target Lesion. If possible, the Target Lesion should 
exclude the elbows and knees. The location of the Target Lesion will be identified using 
an anatomical chart in the source documentation. The size of this lesion (cm²) will be 
calculated, and the TLSS will be evaluated from this lesion.  
To calculate the area of the Target Lesion the Investigator should measure once across its 
widest point and again at a point midway and perpendicular to the widest point. This 
should be done using the cm ruler provided. Measurements should be done to the nearest 
mm and reported in units of cm (i.e., reported as cm out to the first decimal place, not 
reported nor calculated in mm). These two values should be multiplied to give the total 
area of the Target Lesion (cm2).  
The Target Lesion should be used for all future evaluations and severity for individual 
signs and symptoms (scaling, erythema and plaque elevation).  
To be eligible for inclusion at Visit 1, the patient must have all of the following: 
• 
An affected BSA of 5 - 10% (Appendix A) 
• 
A IGA score of 2 (mild) or 3 (moderate) (Appendix C) 
• 
Target Lesion area of at least 5 cm² 
• 
Plaque Elevation Score ≥ 2 for the Target Lesion (based on TLSS score, 
Appendix B) 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 32 of 52 
 
 
9.6.13 Health Status/Adverse Events 
At Visits 2, 3 and 4 patients will be questioned regarding any changes in their medical 
status since their previous visit. Any significant changes observed after randomization 
will be reported as adverse events.  
9.7 
Adverse Events 
The patients will be monitored throughout the study for any Adverse Events. AEs will be collected 
through both solicited and unsolicited means and subsequently coded in tabular form using the 
MedDRA (Version 17 or higher) Adverse Event Dictionary.  The patients will be encouraged to 
report signs, symptoms, and any changes in health to the clinic staff.  Severity of each AE will be 
determined by the staff based on observation and questioning of the patients.  The Investigator will 
judge the relationship of the event to the study treatments. Adverse events should be followed up 
until they have resolved or stabilized. 
9.7.1 
Adverse Event Definitions 
Adverse Event: Any untoward medical occurrence in a patient or clinical investigation 
patient administered a pharmaceutical product and which does not necessarily have a 
causal relationship with treatment. An AE can therefore be any unfavorable and 
unintended sign, symptom, or disease, temporally associated with the use of a medicinal 
(investigational) product, whether or not related to this product. This includes events not 
seen at baseline, or worsened even if present at baseline.  
Unexpected Adverse Event: An adverse event where the nature or severity of is not 
consistent with the applicable product information (e.g., Investigator’s Brochure for an 
unapproved investigational product or package insert/summary of product characteristics 
for an approved product).  
Adverse Drug Reaction: All noxious and unintended responses to a medical product 
related to any dose should be considered adverse drug reactions. The response to a 
‘medical product’ means that a causal relationship between a medicinal product and an 
adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out. 
9.7.2 
Severity of Adverse Event 
The severity of the adverse event will be graded by the Investigator using the following 
criteria as guidelines:  
• 
MILD: Awareness of symptom but does not interfere with routine activities.  
• 
MODERATE: Discomfort sufficient to interfere with routine activities.  
• 
SEVERE: Impossible to perform routine activities. 
9.7.3 
Relationship of Adverse Event 
Relationship to the Study Product 
• 
NOT RELATED: Any AE that is clearly not related to use of the study drug. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 33 of 52 
 
 
• 
POSSIBLE: The association of the AE with the study drug is unknown; however, 
a relationship between the drug and event cannot be ruled out.  
• 
PROBABLE: There is reasonable temporal relationship between the use of the 
study drug and the AE. Based upon the Investigator’s clinical experience, the 
association of the event with the study drug seems likely.  
• 
DEFINITE: The AE occurs following the application of the study drug and it 
cannot be reasonably explained by any other known characteristics of the 
patient’s clinical state, environmental or toxic factors, or other modes of 
treatment administered to the patient. It disappears or decreases upon 
discontinuation of the study medication and reappears on a re-challenge of the 
study drug. 
9.7.4 
Patient’s Participation Stopping Criteria 
In the opinion of the Investigator, if the patient suffers an AE that warrants discontinuation 
of the study drug because of interference with age-appropriate instrumental ADL 
(Activities of Daily Living), for example preparing for meal, shopping for groceries or 
clothing, using the telephone, etc. the patient will be followed until the AE resolves or is 
considered stable. Any subject that discontinues the study because of  an adverse event will 
be followed until resolution or stabilization of the adverse event.   
 
9.8 
Serious Adverse Events 
9.8.1 
Definition of a Serious Adverse Event 
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose 
suggests a medically significant hazard, including any event that: 
• 
Results in death – includes all deaths, even those that appear to be completely 
unrelated to study treatment (e.g., car accident where patient is a passenger). 
• 
Is life–threatening – in the view of the Investigator, the patient is at immediate risk of 
death at the time of the event. 
• 
Results in persistent or significant disability or incapacity (substantial disruption of 
one’s ability to conduct normal life). 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
• 
Causes congenital anomaly or birth defect. 
• 
Is an important medical event that may not be immediately life-threatening or result 
in death or hospitalization, but may jeopardize the patient or may require medical or 
surgical intervention to prevent one of the serious outcomes listed above (e.g., 
intensive treatment in an emergency room, convulsions that do not result in 
hospitalizations). Emergency Room visits that require medical or surgical 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 34 of 52 
 
 
intervention to prevent one of the other serious outcomes listed above are considered 
a Serious Adverse Event. 
9.8.2  Reporting Serious Adverse Events 
Investigator Reporting of SAEs 
Adverse events which are evaluated by the Investigator as "Serious" will be reported to 
the Sponsor and IRB within 24 hours of notice whether or not they are considered 
expected or drug-related. All SAEs will be reported as per applicable regulations. All 
SAEs encountered during the study will be reported on the appropriate form and 
summarized in the final report.  
Any serious or unexpected adverse events should be reported to Novum within 24 
hours. Following is the contact information: 
Gail Gongas 
Vice President, Clinical Trials 
Cell Phone 412-606-1603 
Phone 412-363-3300 x 522 
Fax 412-291-3171 
Or 
Paolo Maria Fanzio, MD 
Medical Monitor 
Pittsburgh, PA 15206 
Phone: 412-363-3300 x597 
Fax: 412-291-3171 
Novum will report any Serious Adverse Event to Taro.  
Documentation should be sent to Taro’s Study Manager and/or Taro’s Drug Safety 
Department listed below:  
Taro Study Manager: 
Danielle Simpson 
Coordinator, Clinical Operation 
Phone: (914) 345-9001 x6234 
Email:  danielle.simpson@Taro.com 
 
Taro Drug Safety Manager: 
Margo Lacy Wyatt, RN, BSN, 
Drug Safety Manager, Medical Affairs 
Phone: 914-345-9001 Ext. 6758 
Email: Margo.Wyatt@taro.com 
and TAROPVUS@TARO.com 
Investigators will be informed of any SAEs reported at other study sites within 15 days from the 
initial report.  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 35 of 52 
 
 
10.0 
STATISTICAL METHODS 
10.1 
Statistical Plan 
A Statistical Analysis Plan (SAP), detailing the intended statistical analysis of the study 
data, will be prepared as a separate document and finalized before database lock. Any 
deviation from the original statistical plan will be described and justified in the final 
report, as appropriate. The procedure for accounting for missing, unused and spurious 
data will be included in the Statistical Analysis Plan. 
All statistical analysis will be conducted using SAS®, Version 9.4 or higher. 
10.2 
Determination of Sample Size 
The primary analyses of interest are the proportion of patients in the Test and Vehicle 
treatment groups who are considered to be a Clinical Success and Treatment Success on 
Day 28.  
In-house data from two Phase III studies that evaluated the safety and efficacy of 
desoximetasone spray 0.25% (twice daily for 28 days) in patients with moderate to severe 
plaque psoriasis were used for sample size determination. These studies were conducted in 
support of Taro’s NDA #204141, Topicort® (desoximetasone) Topical Spray, 0.25%. In 
those studies the Clinical Success rates were 31% and 53% for the active product (42% 
average) and 5% and 18% for the vehicle treatment (12% average), and the Treatment 
Success rates were 39% and 53% for the active product (46% average) and 7% and 17% for 
the vehicle treatment (12% average).  
Based on the average results from these two studies on the 0.25% spray, the proportion of 
subjects in the Test group considered a Clinical Success and Treatment Success is expected 
be 40% or higher and the proportion of subjects in the Vehicle group considered a Clinical 
Success and Treatment Success is expected to be 12% or less for desoximetasone spray 
0.15% in patients with mild to moderate plaque psoriasis. With these assumptions, 50 
evaluable subjects in the ITT in each treatment group will demonstrate superiority of the 
Test to the Vehicle group with 89% power at the 5% level of significance (p < 0.05, using 
two-sided  Z-test), assuming 100% correlation between Clinical and Treatment Success 
rates. 
To allow for patients who may drop out from the study or are otherwise non-evaluable, up 
to 120 patients may be enrolled (60 in the Test group and 60 in the Vehicle group). 
10.3 
Study Populations 
10.3.1 Intent-to-Treat (ITT) Population 
The ITT population will include: 
• 
All randomized subjects.  
Patients discontinued early for any reason will be included in the ITT with their 
Last Observation Carried Forward (LOCF). 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
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10.3.2 Per-Protocol (PP) Population 
 
 
 
The PP population is a sub-population of the ITT population and will include: 
• 
Patients who met all inclusion and exclusion criteria and were randomized 
according to the randomized treatment assignment. 
• 
Patients who applied at least one dose AND had at least one post-baseline 
evaluation. 
• 
Patients who were compliant with the dosage regimens following 
randomization. 
• 
Patients who had no major protocol deviations. 
10.3.3 Safety Population 
• 
All patients who were randomized and applied at least one dose of the study 
product. 
10.4 
Baseline Comparability 
Baseline comparability of all treatment groups will be evaluated separately in the ITT, PP 
and Safety populations. Comparative analyses will use appropriate statistical tests (e.g., 
one-way analysis of variance, Cochran-Mantel-Haenszel Test).  
The following baseline demographics (determined from their initial study visit) will be 
evaluated: 
• 
Age (years) 
• 
Gender (male/female) 
• 
Ethnicity (Hispanic/non Hispanic) 
• 
Race (White, Black/African American, Native Hawaiian or Other Pacific 
Islander, Asian, American Indian or Alaska Native, Other) 
• 
Baseline total BSA  
• 
Baseline % BSA affected with psoriasis 
• 
IGA score 
• 
TLSS Score  
• 
PASI Score 
• 
Target Lesion size (area) 
Descriptive statistics by treatment group will be presented. 
10.5 
Efficacy Endpoints 
Primary Efficacy Endpoints 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 37 of 52 
 
 
1. The proportion of patients in each treatment group who are considered a Clinical 
Success at Day 28 ± 2 (i.e., at least a 2-grade improvement from the patient’s 
baseline IGA score).  
2. The proportion of patients in each treatment group who are considered a 
Treatment Success for the Target Lesion at Day 28 ± 2 (i.e., a TLSS value of 0 or 
1 at Day 28 ± 2 for each of the three signs and symptoms (i.e., erythema, scaling 
and plaque elevation) depending on the patient’s baseline TLSS). 
Definitions: 
1. Treatment Success: To be considered a Treatment Success the patient’s TLSS 
value at Day 28 ± 2 must be 0 if their baseline TLSS value is 2 and must be 0 or 
1 if their baseline TLSS value is > 2 for each of the individual signs and 
symptoms 
2. Treatment Failure: A patient will be considered a Treatment Failure if: 
a. the patient’s TLSS value is > 0 if their baseline TLSS value is 2 or > 1 if 
their baseline IGA score is > 2 for any of the individual signs and 
symptoms 
b. the patient was considered to have an insufficient therapeutic response 
3. Clinical Success: To be considered a Clinical Success the patient must have at 
least a 2-grade improvement from their baseline IGA score. That is, an IGA score 
of 0 at Day 28 ± 2 if their baseline IGA score is 2 or an IGA score of 0 or 1 at 
Day 28 ± 2 if their baseline IGA score is 3 
4. Clinical Failure: A patient will be considered a Clinical Failure if: 
a. the patient’s IGA score is > 0 if the baseline IGA score is 2 or > 1 if the 
baseline IGA score is 3 
b. the patient was considered to have an insufficient therapeutic response 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
1. The proportion of patients with a baseline IGA score of 3 who are considered a 
Clinical Success. 
2. The proportion of patients with a baseline IGA score of 3 who are considered a 
Treatment Success. 
3. The proportion of patients with a baseline IGA score of 2 who are considered a 
Clinical Success. 
4. The proportion of patients with a baseline IGA score of 2 who are considered a 
Treatment Success. 
5. The change from baseline in %BSA affected at Day 28 ± 2 will be evaluated as a 
secondary endpoint. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 38 of 52 
 
 
10.6 
Primary Efficacy Analyses 
The Test treatment will be compared with Placebo for each primary endpoint at the 5% 
significance level (p < 0.05; two-sided, Cochran-Mantel-Haenszel exact test) in the ITT 
population using last observation carried forward (LOCF). Superiority of Test over 
Placebo will be demonstrated if both dichotomous endpoints show statistical significance 
at the 5% significance level.  
For sensitivity testing, the primary analysis will also be performed using the PP 
population. 
10.7 
Secondary Efficacy Analyses 
The Test treatment will be compared with Placebo for each dichotomous secondary 
endpoint at the 5% significance level (p < 0.05; two-sided, Cochran-Mantel-Haenszel 
exact test) in the ITT population using LOCF.  
The Test treatment will be compared with Placebo for the continuous secondary endpoint 
at the 5% significance level in the ITT population using LOCF. Analysis of Covariance 
(ANCOVA) with treatment and site as fixed effects and baseline %BSA as a covariate in 
the model will be used for the evaluation of the continuous secondary endpoint. 
For the secondary efficacy analyses, superiority of Test over Placebo will be considered 
supported for each endpoint if the difference is statistically significantly greater than 0 at 
the 5% significance level. There will be no multiplicity adjustment for the evaluation of 
the five secondary endpoints. 
Descriptive statistical analysis will be generated to compare the efficacy results in each 
treatment group at each visit. 
10.8 
Treatment-by-Site Interaction and Pooling of Clinical Sites 
As this is a multiple-site study, the interaction of treatment-by-site may be evaluated for 
superiority testing by the Breslow-Day test for homogeneity of the odds ratio at the 5% 
significance level (p < 0.05) for the primary efficacy endpoints in the ITT population. A 
site(s) with a low enrollment rate(s) may be pooled with its geographically closest site, so 
as to avoid bias in the estimation of a treatment-by-site interaction effect. The pooling 
will be done for low enrolling sites that account for less than 4-7% of the total number of 
patients at the site with the highest enrolling rate in the ITT population. If no treatment-
by-site interaction is identified with the primary endpoints then no adjustment will be 
made to any efficacy analysis and treatment-by site interaction will not be included as a 
term in the statistical models for evaluating superiority. 
10.9 
Safety Analysis 
Adverse events (AEs) will be classified using standard MedDRA terminology Version 
17.0 or higher and summarized by treatment group. Summary tables comparing the type, 
incidence, severity will be prepared by treatment group. The relationship of AEs, if any, 
to the study drug will be assessed by the Investigator.  All AEs will be presented 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 39 of 52 
 
 
regardless of suspected causality.  The frequency, severity and relationship to study drug 
for AEs in each treatment group will be used to evaluate the safety profile of the test 
product. 
11.0 
REGULATORY OBLIGATIONS 
11.1 
Institutional Review Board 
The study protocol, informed consent/assent form, Investigator's Brochure, or package 
insert (as applicable), and any specific advertising will be submitted to, and approved by, 
an Institutional Review Board (IRB) before the start of the study. A form must be signed 
by the chairman or designee of the IRB noting the approvals. This notification of the 
board's approval along with a description by profession and gender of the board's 
composition will be provided to the Sponsor. 
11.2 
Study Documentation 
This study will be conducted in compliance with the protocol, Good Clinical Practices 
(GCPs) and all applicable regulations, including the Federal Food, Drug and Cosmetics 
Act, US applicable Code of Federal Regulations (title 21), parts 50, 56, 312, 320 and any 
IRB requirements relative to clinical studies and the Declaration of Helsinki, June 1964, 
as modified by the 59th World Medical Association General Assembly, October 2008.16-18 
The Investigator will permit trial-related monitoring, audits, IRB review and regulatory 
inspections providing direct access to source data/documents. 
11.2.1 Protocol  
The Investigator indicated on FDA Form 1572 will act as the Principal 
Investigator at each study site. Protocols will be noted as approved by placement 
of the Novum Representative’s signature on the cover page. The Sponsor of the 
study will also approve the protocol by having a study-responsible individual 
sign the protocol cover page.  
11.2.2 Informed Consent 
An Informed Consent Form (ICF) that includes all of the relevant elements 
currently required by FDA and local State regulations will be provided to each 
prospective study patient before enrollment into the study. The type and method 
of study, tests to be administered, any potential or possible hazards, and the 
patient's right to withdraw from the study at any time will be explained to the 
patients by the Investigator or designee. Once the Investigator or designee is 
assured that an individual candidate understands the implications of participating 
in this study, the patient will be asked to give consent by signing and dating in 
the appropriate areas of the ICF. The Investigator or designee will also sign and 
date the form, along with a staff member who will sign the ICF as a witness to 
verify that the patient has indeed received information. For illiterate patients, 
verbal consent should be obtained in the presence of and be countersigned by a 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 40 of 52 
 
 
literate witness. If any other language is required, translation will be performed 
by a certified translator. A copy of the ICF will be provided to the patient. 
11.2.3 Protocol and Informed Consent Changes 
Revisions to the original protocol will be documented in amendments, 
incorporated as a preface to the new version and approved by the IRB. Any 
revision that substantially alters the study design or increases potential risk to the 
patient requires the patient’s consent to continue in the study. Revisions to the 
original ICF will also be approved by the IRB. The approvals will be processed 
in accordance with the established IRB procedures. Copies of all protocol and 
ICF amendments/revisions, along with letters noting IRB approval, will be 
submitted to the Sponsor. 
11.2.4 Source Documents and Case Report Forms 
All patients will be identified by initials, date of birth, and a unique patient 
number. Source documents will be used to record all study-related data. Source 
document entries will be used to complete Case Report Forms (CRFs). A set of 
CRFs will be completed for each patient enrolled in the study. All data and CRFs 
will be reviewed, evaluated and signed by the Investigator, as required. 
The original source documents and a copy of the corresponding CRFs will be 
retained by the Investigator. Patients who terminate early from the study will 
have the Visit 4 (end of treatment) source/CRF completed. 
11.2.5 Drug Accountability 
All drug receipt, inventory, dispensing, dosing and reconciliation records will be 
maintained in compliance with Federal Regulations. The study drug will be 
dispensed to qualified study patients according to established procedures. At the 
end of the study (after the database has been locked) all used and unused study 
medication will be returned to Sponsor or designee. 
11.2.6 Drug Storage 
All study medication will be stored at controlled room temperature 15-30°C (59-
86ºF), in a secure place with access by authorized individuals only. The 
Investigator will be responsible for maintaining accurate records of drug receipt, 
dispensing, and return.  At the end of the study, all partially used and unused 
study medication will be returned to Sponsor or designee. 
11.2.7 Pregnancies 
Patients with a positive pregnancy test during screening will not be enrolled in 
the study. Patients who report that they have become pregnant during the study or 
have a positive pregnancy test at Visit 4 will be followed to completion of the 
pregnancy. The pregnancy will be reported as an AE. 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 41 of 52 
 
 
Female patients of childbearing potential must have been using and must agree to 
continue to use accepted methods of birth control, throughout the study. All 
female patients are considered to be of childbearing potential unless they are 
premenarchal, have been surgically sterilized or have been postmenopausal for at 
least 1 year. Abstinence is an accepted method of birth control. Alternatively, any 
of the following methods of birth control are acceptable: oral contraceptives, 
contraceptive patches/implants (e.g., Norplant®), Depo-Provera®, double barrier 
methods (e.g., condom and spermicide) or IUD. Before study enrollment women 
of child bearing potential must be advised of the importance of avoiding 
pregnancy during study participation.  
A negative result of a urine pregnancy test having a minimum sensitivity of at 
least 25 mIU/ml for hCG should be obtained, before study participation. 
Pregnancy testing will be performed at Visits 1 and 4 and the results of all 
pregnancy tests (positive or negative) will be documented. 
If following initiation of study treatment, it is subsequently discovered that a 
study patient is pregnant or may have been pregnant at the time of study product 
exposure, the study product will be permanently discontinued. The Principal 
Investigator must immediately notify the Medical Monitor of this event. 
Protocol-required procedures for study discontinuation and follow-up must be 
performed on the patient. Other appropriate pregnancy follow-up procedures 
should be considered if indicated. In addition, the Principal Investigator must 
report to the sponsor follow-up information regarding the course of the 
pregnancy, including perinatal and neonatal outcome. Infants should be followed 
for a minimum of eight weeks after birth. 
 
11.2.8 Reporting Safety Information to the IRB 
The Investigator must promptly report to the Investigator’s IRB all unanticipated 
problems involving risks to patients. This includes death from any cause and all 
serious adverse events occurring during the study, regardless of the assessed 
causality.19 
11.2.9 Record Retention 
All drug accountability records, CRFs, source data and related regulatory 
documents must be retained for at least ten years following completion of the 
study or for two years after the test product has been approved for marketing by 
the Food and Drug Administration.  
11.2.10 Study Monitoring and Auditing 
Novum will be responsible for monitoring the study according to Good Clinical 
Practice and applicable regulations. Monitoring visits are for the purpose of 
confirming adherence to the protocol and to verify complete and accurate data 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 42 of 52 
 
 
collection. The clinical site will make all records associated with the study 
available to Novum’s representative during such visits and audits 
The study may be subject to audit by the Sponsor, Sponsor Representative or by 
regulatory authorities. If such an audit occurs the Investigator must agree to 
allow access to required patient records. By signing this protocol, the Investigator 
grants permission to personnel from the Sponsor, its representatives and 
appropriate regulatory authorities for on-site monitoring of all appropriate study 
documentation, as well as on-site review of study procedures. 
11.2.11 End of the Trial 
The end of the trial is defined as the time at which the last patient has completed 
their last visit in the study.  Upon completion of the study, the study drug will no 
longer be available to the patient but the Investigator can, at their discretion, 
discuss alternative treatments with the patient. 
11.2.12 Clinical Study Report 
At the end of the study a full report per requirements of Sponsor and regulatory 
authorities will be prepared which will include a narrative of the clinical conduct 
and results of the study, a statistical report including a description of the analysis 
performed, and other documentation as may be appropriate. The report will be in 
electronic format according to eCTD and ICH formatting standards and 
guidelines.20 ANDA summary tables will also be generated. Data sets will be 
provided in SAS® transport (.xpt) format with appropriate description (Read Me) 
files as required by FDA.  
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 43 of 52 
 
 
12.0 
REFERENCES 
1 
www.psoriasis.org. 
2 
National Clinical Guideline Centre, U. Assessment and management of psoriasis. NCGC 
Guideline (2012). 
3 
Jacob, S. Corticosteroid and Fragrance Allergy Exacerbating Scalp Psoriasis. J Clin Aesthet 
Dermatol 7, 54-55 (2014). 
4 
Feldman, S. R. & Krueger, G. G. Psoriasis assessment tools in clinical trials. Annals of the 
rheumatic diseases 64 Suppl 2, ii65-68; discussion ii69-73, doi:10.1136/ard.2004.031237 (2005). 
5 
Louden, B. A., Pearce, D. J., Lang, W. & Feldman, S. R. A Simplified Psoriasis Area Severity 
Index (SPASI) for rating psoriasis severity in clinic patients. Dermatology online journal 10, 7 
(2004). 
6 
Augustin, M. et al. Topical long-term therapy of psoriasis with vitamin D(3) analogues, 
corticosteroids and their two compound formulations: position paper on evidence and use in daily 
practice. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society 
of Dermatology : JDDG 12, 667-682, doi:10.1111/ddg.12396 (2014). 
7 
Samarasekera, E. J., Sawyer, L., Wonderling, D., Tucker, R. & Smith, C. H. Topical therapies for 
the treatment of plaque psoriasis: systematic review and network meta-analyses. The British 
journal of dermatology 168, 954-967, doi:10.1111/bjd.12276 (2013). 
8 
Pharmaceuticals, T. Package Insert for TOPICORT® (desoximetasone) Topical Spray, 0.25%.  
(2013). 
9 
Luger, T. A. et al. A study of the safety and efficacy of calcipotriol and betamethasone 
dipropionate scalp formulation in the long-term management of scalp psoriasis. Dermatology 
217, 321-328, doi:10.1159/000155642 (2008). 
10 
Novum. A Randomized, Evaluator Blinded, Within Subject, Single-Center Evaluation of the 
Vasoconstrictive Properties of Desoximetasone 0.25% Spray Compared to Seven Other 
Corticosteroids of Known Potency and a Placebo in Healthy Volunteers Protocol #10715005 Data 
on File. 
11 
Novum. A Double-Blind, Vehicle-Controlled, Randomized, Dose-Ranging, Multiple-Site Clinical 
Study to Evaluate the Efficacy and Safety of Desoximetasone Topical Sprays (0.05%, 0.25%) in 
Patients with Moderate to Severe Plaque Psoriasis: Protocol #70915004 Data on File. 
12 
FDA. Summary Basis of Approval for Clobex Spray, 0.05%; NDA# 021835.  (2005). 
13 
ICH. Choice of Control Group and Related Issues in Clinical Trials E10.  20 July (2000). 
14 
Penslar. IRB Guidebook, Office for Human Rights Protection. US Department of Health and 
Human Services (1993). 
15 
FDA. Draft Guidance for Industry: Topical Dermatological Drug Product NDAs and ANDAs ---
In Vivo Bioavailability, Bioequivalence, In Vitro Release, and Associated Studies. U.S. 
Department of Health and Human Services, Center for Drug Evaluation and Research (CDER) 
(1998). 
16 
FDA. 21CFR 320 Procedures for Determining the Bioavailability or Bioequivalence of Drug 
Products. Department of Health and Human Services, Subchapter D-Drugs for Human Use 5 
(2014). 
17 
FDA. 21CFR Part 50 Protection of Human Subjects. Department of Health and Human Services, 
Subchapter A-General 1 (2014). 
18 
FDA. 21CFR Part 56 Institutional Review Boards. Department of Health and Human Services, 
Subchapter A-General 1 (2014). 
19 
FDA. 21CFR 312.32: IND Safety Reporting.  (2010). 
20 
ICH. Structure and Content of Clinical Study Reports E3.  Step 4 version (1996). 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 44 of 52 
 
 
21 
Mosteller, R. D. Simplified calculation of body-surface area. The New England journal of 
medicine 317, 1098, doi:10.1056/NEJM198710223171717 (1987). 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 45 of 52 
 
 
13.0 
APPENDICES 
13.1 
Appendix A 
Total Body Surface Area Calculation 
To calculate the Total BSA the following procedure (Mosteller Formula )21 should be followed. 
 
Total Body Surface Area (BSA) in meters squared  
     
m2   = ((height (cm) x weight (kg)) /3600)½ 
 
Patient’s height and weight should preferably 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 
 
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 calculate the %Body Surface Area Affected the “Rule of Nine” will be used. 
 
Body Surface Area affected will be calculated using the standard medical procedure of the 
“Rule of Nines”. (5) The patient’s palm surface of the hand represents approximately one 
percent of his/her body surface area. (5) Calculate to the nearest whole percentage. 
 
 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 46 of 52 
Part
10-14 year child body 
% of total 
Adult body 
% of total 
Arm 
9.5% 
9% 
Head 
12% 
9% 
Neck 
1% 
1% 
Leg 
18% 
18% 
Anterior trunk 
16% 
18% 
Posterior trunk 
16% 
18% 
 
 
 
 
 
 
 
 
To be eligible for inclusion in the study a patient must have a % BSA affected of 5-10% 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 47 of 52 
 
 
13.2 
Appendix B 
 
TOTAL LESION SEVERITY SCORE (TLSS) 
 
Score 
Grade 
Erythema 
Scaling 
Plaque Elevation 
0 
Clear 
No evidence of 
erythema 
No evidence of scaling 
No evidence of plaques 
above normal skin level 
1 
Almost Clear 
Pink discoloration, 
minimal erythema 
Occassional fine scales 
hardly noticeable 
Slight, just discernable 
elevation above normal skin 
level 
2 
Mild 
Light red coloration 
Slight but definite 
roughness, fine scale 
present, no cracking 
Discernable elevation above 
normal skin level upon 
examination, but not 
pronounced 
3 
Moderate 
Moderate redness, 
but not dark 
Moderate roughness, 
somewhat coarse 
scaling 
Definite plaque formation 
with rounded/sloped edges 
to plaque 
4 
Severe 
Dark red coloration 
Marked roughness, 
coarse/thick scaling, 
cracking may be 
evident 
Marked elevation with hard, 
distinct edges to plaque 
5 
Very Severe 
Very dark red 
coloration with 
induration present 
Very thick scales 
covering extensive 
area, severe 
cracking/fissures may 
be evident 
Very marked elevation, 
very hard and sharp edges 
to plaque 
 
 
To be considered for inclusion in the study, the Target Lesion must have a minimum plaque elevation 
score of ≥ 2. 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 48 of 52 
 
 
13. 3 
Appendix C 
 
INVESTIGATOR’S GLOBAL ASSESSMENT (IGA) 
To be eligible for inclusion in the study the IGA must be 2 - 3 at baseline.  
 
Score 
Category 
Description 
0 
Clear 
Plaque: elevation: no evidence of plaque elevation above normal skin level. 
Scaling:  no evidence of scaling 
Erythema: no redness 
1 
Minimal 
Plaque elevation: very slight elevation above normal skin level, easier felt than 
seen 
Scaling : limited amount of very fine scales partially covers some of the plaques 
Erythema: very few of the plaques are light red 
2 
Mild 
Plaque elevation: slight but definite elevation above the normal skin level, 
typically with edges that are indistinct or sloped on some of the plaques. 
Scaling: mainly fine scales, some plaques are partially covered. 
Erythema: some plaques are light red 
3 
Moderate 
Plaque elevation: moderate elevation with rounded or sloped edges on most of 
the plaques 
Scaling: somewhat coarser scales; most plaques are partially covered. 
Erythema: most plaques are red 
4 
Severe 
Plaque elevation: marked to very marked elevation, with hard to very hard sharp 
edges on virtually all or all of the plaques. 
Scaling: coarse, thick scales; virtually all or all plaques are covered; rough 
surface. 
Erythema : virtually all or all plaques are bright to dusky red. 
 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 49 of 52 
 
 
13.4  Appendix D 
PSORIASIS AREA SEVERITY INDEX (PASI) 
The PASI is a composite score based on the severity of three different clinical signs of 
psoriasis in four different areas of the body multiplied by the percent of that specific body 
area affected multiplied by a weighting factor.   
 
Erythema, Induration, Scaling will be evaluated using the severity scale below: 
0 = Clear 
 
 
 
 
1 = Mild 
 
 
 
 
2 = Moderate 
 
 
 
 
3 = Severe 
4 = Very Severe  
 
 
PASI Score  
The PASI score is calculated as follows: 
Head/neck 
(E + I + S) x Area x 0.1  
Upper Limbs 
(E + I + S) x Area x 0.2 
Trunk  
(E + I + S) x Area x 0.3 
Lower Limbs 
(E + I + S) x Area x 0.4  
PASI SCORE = SUM OF ABOVE 4 REGIONS 
 
E: 
Erythema,  
I:  
Induration 
S: 
Scaling 
 
Severity is based on the Investigator’s assessment of individual signs and symptoms 
0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe using the definitions above 
 
The % of each body region affected is scored as the variable Area above in the PASI 
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%  
 
PASI 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.  


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 50 of 52 
 
 
13.5 
Appendix E 
APPLICATION SITE REACTIONS 
The following application site reactions will be evaluated at each visit based on the scale provided below: 
Burning 
Erosion 
Edema 
Pain 
Itching 
Dryness 
 
Absent  
0 
Mild 
 
1  
(slight, barely perceptible) 
Moderate 
2  
(distinct presence) 
Severe  
3  
(marked, intense) 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 51 of 52 
 
 
13.6 
Appendix F 
Amendments to the Protocol 
Revision 
Date 
 
1 
07/29/15 
The following revisions were made to the protocol, Revision 0,  dated 02/25/15: 
• 
Study schematic was updated to acknowledge that 1 designated site will take photographs of a 
target area 
• 
The study age range was updated to include patients 12 years of age and older 
• 
Section 7.5 was updated to include justification to begin enrollment in the adult (18 and older) 
population 
• 
Follow-up phone call (Visit 5) added 
• 
Inclusion Criteria #4 was updated to clarify enrolled of 5-10% BSA affected 
• 
Patient stopping criteria was added to Section 9.7.4 
• 
Section 10.5 was updated regarding the secondary endpoints 
• 
Updates were make to Section 10.6 and 10.7 regarding the Primary and Secondary Analysis 
• 
ITT definitation was revised in Section 10.3.1 
• 
PP Population was added in Section 10.3.2 
• 
TLSS scale added (Appendix B) 
• 
PGA scale was updated to an IGA scale (Appendix C) 
• 
PASI scale was added (Appendix D) 
• 
Application Site Reactions were added to the protocol (Appendix E) 
 
 
Revision 
Date 
 
2 
11/04/15 
The following revisions were made to the protocol, Revision 0,  dated 02/25/15: 
• 
Novum address was updated 
• 
A correction was made to section 9.6.8 
• 
Taro SAE contact information was updated 
 
Revision 
Date 
 
3 
01/04/16 
The following revisions were made to the protocol, Revision 2,  dated 11/04/15: 
• 
Primary efficacy language was updated 
• 
Definition of Clinical Success/Failure and Treatment Success/Failure was updated 
 
 
Revision 
Date 
 
4 
02/24/16 
The following revisions were made to the protocol, Revision 3  dated 01/04/16: 
• 
Minor typographical errors were corrected and clarified 
 
 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multiple-Site Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone Topical Spray, 0.15% (Taro Pharmaceuticals, 
U.S.A., Inc.) in Patients with Mild to Moderate Plaque Psoriasis
 
 
71542603 Rev. 5  February 15, 2017  Taro Pharmaceuticals U.S.A., Inc.  Page 52 of 52 
 
 
Revision 
Date 
 
5 
02/15/17 
The following revisions were made to the protocol, Revision 5, dated 02/24/16: 
• 
Novum and Sponsor representative information was updated. 
• 
Added secondary endpoints and corresponding analysis methods. 
• 
Revised the analysis method for the primary endpoints. 
• 
Corrected minor typographical errors in Appendix D. 
 

SAP_001.pdf: