Clinical trial NCT02933866
Conditions: Scalp Psoriasis
Sponsor: Sun Pharmaceutical Industries, Inc.
Start date: 2016-03-11; Completion date: 2017-09-29
Enrollment: 371 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to Evaluate the Efficacy and Safety of DSXS topical product in Patients with Mild to Severe Scalp Psoriasis

Detailed description:
To evaluate the therapeutic efficacy and safety of DSXS topical product (Taro Pharmaceuticals, U.S.A., Inc.) compared to a Vehicle topical product (Taro Pharmaceuticals, U.S.A., Inc.) in patients with mild to severe scalp psoriasis.

Arms: arm 1: applied once daily for 28 days arm 2: applied once daily for 28 days
Interventions: intervention 1: DSXS topical intervention 2: Vehicle topical
Intervention descriptions: intervention 1: topical treatment intervention 2: topical treatment

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
1.0 
TITLE PAGE 
Drug Product 
Population 
Study Design 
Sponsor 
Protocol Number 
Novum Study Number 
IND# 
Protocol Date 
Rev 1 Date 
Rev 2 Date 
Desoximetasone 0.25% Shampoo 
Up to (370) patients (18 years of age or older) with mild to severe 
plaque psoriasis of the scalp 
A Randomized Double-Blind, Vehicle-Controlled, Parallel-
Design, Multiple-Site, Phase III Clinical Study 
Taro Pharmaceuticals U.S.A., Inc. 
DSXS 1536 
71515013 
124879 
02/10/2016 
02/24/2016 
05/3112016 
This document is a confidential communication of Novum Pharmaceutical Research Services. Receipt of 
this document constitutes an agreement hy the recipient that no unpublished infbrmation contained herein 
will he disclosed without Novum's written approval. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 1 of 48 
 
NIIRB 
June 7, 2016 
APPROVED 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
2.0 
KEY STUDY PERSONNEL AND FACILITIES 
Sponsor: 
CRO: 
Sponsor's Representative: 
CRO Representative 
Medical Monitor: 
Biostatistician: 
Taro Pharmaceuticals U.S.A., Inc. 
3 Skyline Drive, 
Hawthorne, NY 10532 
Novum Pharmaceutical Research Services (Novum) 
225 W. Station Square Drive, Suite 200 
Pittsburgh, PA 15219 
Natalie Yantovskiy 
Director, Clinical 
Taro Pharmaceuticals U.S.A., Inc. 
Phone: 914-345-9001 Ext 6849 
Fax: 914-593-0078 
Email: Natalie.Yantovskiy@Taro.com 
Gail Gongas 
Vice President, Clinical Trials 
Novum Pharmaceutical Research Services 
Tel: 412-363-3300 x 522 
Fax: 412-362-5783 
Email: gdgongas@novumprs.com 
Paolo Maria Fanzio, MD 
Medical Monitor 
Novum Pharmaceutical Research Services 
Tel: 412-363-3300 x 597 
Fax: 412-924-0522 
Email: pmfanzio@novumprs.com 
Jianhua Liu, MSc 
Senior Biostatistician 
Novum Pharmaceutical Research Services 
Tel: 613-483-6836 
Email: jliu@novumprs.com 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 2 of 48 


CONFIDENTIAL PRO'l'OCOL 
A Randomit:Gd, Double·-Biind, Vchiclc-Conlro!kd, Parallel-Design, Multiple-Site, Pll<I>C Ill Clinical Study to 
Evaluate tlw EW!cacy ami Safely ofDe~oximcrasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
SIGNATlJRE PAGE 
We, the undersigned, have carefully read this protocol and agree that it contains a! I the neecssnry 
tnform:~tion required to conduct the study. The study will be performed according to this protowl, 
all applicable FDA regulations, ICH guidelines and Good Clinical Practice standards. 
(Jail Gongas 
Vice President, C!inicnl Trials 
Novum Pharmaceutical Research Servic:t~s 
,:-f;:!;f:}!f;~---
Mcdicn! Monitor 
Novum Pharmaceutical Research Services 
Keith D. Gallicano, PhD 
Vice President, Scicntifit: Affairs 
Novum Pharmaceutical Research Services 
Natalie Yantovskiy 
Director, Clinical 
Taro Pharmaceutical USt\, Inc. 
Dme 
6/to/2-D/6 
·········---·--·--'-'"'"t-""""""--~-~-····· 
Date 
Date 
2016.07.20 14:48:41 -04'00' 
Date 
7151501.1 Rev. 2 • ;vlay 3 I, :10 16• 'f:cmJ PhamJacc•Hicals • l'a~;,e :l of'48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
PRINCIPAL INVESTIGATOR'S SIGNATURE 
__________________ , agree to conduct protocol DSXS 1536 Rev 2 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, USA) or Novum Pharmaceutical Research Services, the company managing the study. 
Principal Investigator 
Date 
715 15013 Rev. 2 • May 3 I, 20 16• Taro Pharmaceuticals • Page 4 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
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 ................................................................................................................... 13 
6.0 
LIST OF ABBREVIATIONS AND TERMS ................................................................................. 14 
7.0 
INTRODUCTION .......................................................................................................................... 15 
7.1 
Disease Being Treated ................................................................................................................ 15 
7.2 
Availability and Efficacy of Already Approved Therapies ........................................................ 15 
7.3 
Scientific and Statistical Considerations ..................................................................................... 16 
7.4 
Justification for use of Vehicle Shampoo ................................................................................... 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 ofStudy Design ........................................................................................................... 19 
9.3 
Selection of Study Population ..................................................................................................... 19 
9.3.1 
Inclusion Criteria ................................................................................................................. 19 
9.3.2 
Exclusion Criteria ............................................................................................................... 20 
9.3 .3 
Restrictions during the Study .............................................................................................. 22 
9.3 .4 
Removal of Patients from the Study ................................................................................... 24 
9.3.5 
Early Terminations .............................................................................................................. 24 
9.4 
Treat1nents ................................................................................................................................... 24 
9.4.1 
Treatments Administration ................................................................................................. 24 
9.4.2 
Identity of Investigational Product.. .................................................................................... 25 
9.4.3 
Method of Assigning Patients to Treatment Groups ........................................................... 26 
9.4.4 
Study Blind ......................................................................................................................... 26 
9.4.5 
Compliance ......................................................................................................................... 27 
9.5 
Study Conduct ............................................................................................................................. 27 
9.5.1 
Visit I (Day -1 to 1) Baseline/Randomization [First day of application is Day I] ............. 27 
7151 SO 13 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 5 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
9.5.3 
Visit 2 (Day 14 ± 2): Interim Visit... ................................................................................... 28 
9.5.4 
Visit 3 (Day 29 ± 2): End of Study or Early Termination ................................................... 29 
9.6 
Study Procedures ........................................................................................................................ 29 
9.6.1 
Infonned Consent. ............................................................................................................... 29 
9.6.2 
Detnographics ..................................................................................................................... 30 
9.6.3 
Medical History ................................................................................................................... 30 
9.6.4 
Vital Signs ........................................................................................................................... 30 
9.6.5 
Physical Examination and HEENT Examination ............................................................... 30 
9.6.6 
Concomitant Medication Use .............................................................................................. 30 
9.6.7 
Pregnancy Test .................................................................................................................... 30 
9.6.8 
Dispensing Study Product ................................................................................................... 30 
9.6.9 
Collecting Study Product .................................................................................................... 31 
9.6.10 
Dosing Instructions and Diary ............................................................................................ 31 
9.6.11 
Dosing Cmnpliance ............................................................................................................. 31 
9.6.12 
Percent Scalp Affected ........................................................................................................ 31 
9.6.13 
Investigator's Global Assessment (IGA) ............................................................................ 31 
9.6.14 
Skin Safety Assesstnents ..................................................................................................... 31 
9.6.15 
Ocular Discomfort Assessment.. ......................................................................................... 31 
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 ........................................................................................... 33 
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 
I 0.0 
STATISTICAL METHODS ........................................................................................................... 35 
10.1 
Statistical Plan ............................................................................................................................. 35 
10.2 
Determination of Sample Size .................................................................................................... 35 
10.3 
Study Populations ....................................................................................................................... 35 
1 0.3.1 
Intent-to-Treat (ITT) Population ......................................................................................... 35 
I 0.3.2 
Safety Population ................................................................................................................ 35 
71 S 15013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 6 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
10.4 
Baseline C01nparability ............................................................................................................... 36 
10.5 
Efficacy Endpoint ....................................................................................................................... 36 
10.6 
Efficacy Analysis ........................................................................................................................ 36 
1 0.6.1 
Pri1nary Analysis ................................................................................................................. 36 
1 0.6.2 
Sensitivity Analyses ............................................................................................................ 36 
10.7 
Safety Analysis ........................................................................................................................... 37 
11.0 
REGULATORY OBLIGATIONS .................................................................................................. 37 
11.1 
Institutional Review Board ......................................................................................................... 37 
11.2 
Study Docmnentation .................................................................................................................. 37 
11.2.1 
Protocol ............................................................................................................................... 38 
11.2.2 
Infonned Consent ................................................................................................................ 38 
11.2.3 
Protocol and Informed Consent Changes ............................................................................ 38 
11.2.4 
Source Documents and Case Report Forms ........................................................................ 3 8 
11.2.5 
Drug Accountability ............................................................................................................ 39 
11.2.6 
Drug Storage ....................................................................................................................... 39 
11.2.7 
Pregnancies ......................................................................................................................... 39 
11.2.8 
Reporting Safety Information to the IRB ............................................................................ 40 
11.2.9 
Record Retention ................................................................................................................. 40 
11.2.1 0 
Study Monitoring and Auditing ...................................................................................... 40 
11.2.11 
End of the Trial ............................................................................................................... 40 
11.2.12 
Clinical Study Repo11 ...................................................................................................... 40 
12.0 
REFERENCES ............................................................................................................................... 42 
13.0 
APPENDICES ................................................................................................................................ 44 
13.1 
APPENDIX A ............................................................................................................................. 44 
13.2 
APPENDIX B ............................................................................................................................. 45 
13.3 
APPENDIXC ............................................................................................................................. 46 
13.4 
APPENDIX D ............................................................................................................................. 47 
13.5 
APPENDIX E ............................................................................................................................. 48 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 7 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
4.0 
SYNOPSIS 
Protocol Number 
DSXS 1536 
Title 
A 
Randomized, 
Double-Blind, 
Vehicle-Controlled, 
Parallel-Design, 
Multiple-Site, Phase III Clinical Study to Evaluate the Efficacy and Safety of 
Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Objective 
To evaluate the therapeutic efficacy and safety of desoximetasone 0.25% 
shampoo (Taro Pharmaceuticals, U.S.A., Inc.) compared to a Vehicle 
shampoo (Taro Pharmaceuticals, U.S.A., Inc.) in patients with mild to severe 
scalp psoriasis. 
Sponsor 
Taro Pharmaceuticals U.S.A., Inc. 
Study Products 
• 
Test: Desoximetasone shampoo, 0.25% (Taro Pharmaceuticals, U.S.A., 
Inc.) 
• 
Vehicle: Test Vehicle shampoo (Taro Pharmaceuticals, U.S.A., Inc.) that 
contains the same inactive ingredients as the Test product 
Route of 
Topical 
Administration 
Treatment 
1: 1 (Test: Vehicle) 
Randomization 
Patient Population 
Up to 370 patients 18 years of age or older with a confirmed diagnosis of 
mild to severe plaque psoriasis of the scalp, will be enrolled to ensure 332 
patients are available for the primary analysis. 
Study Design 
Randomized, double-blind, vehicle-controlled, multiple-site, parallel-design 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 8 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Study Conduct 
Inclusion Criteria 
Eligible patients will be randomized in a I: I ratio to Test or Vehicle product. 
Patients will complete 3 clinic visits over a 4-week study duration as follows: 
Patients will administer study product once daily for 28 days starting on Day 
I. The product will be left in place on the scalp for 15 minutes. 
During the study patients will visit the clinical center for a total of 3 
scheduled visits: 
• 
Visit I (Day -1 to I): Baseline/ Randomization 
• 
Visit 2 (Day 14 ± 2): Interim Visit 
• 
Visit 3 (Day 29 ± 2): End of Study or Early Termination 
Plaque psoriasis of the scalp will be evaluated at each visit based on 
dermatologic assessments including Investigator's Global Assessment (IGA) 
score. 
I. Male or non-pregnant, non-lactating females 18 years of age and older. 
2. If female and of child-bearing potential, have a negative urine pregnancy 
test at the baseline/randomization visit and prepared to abstain from 
sexual intercourse or use a reliable method of contraception during the 
study (e.g., condom with spermicide, IUD, oral, injected, transdermal or 
implanted hormonal contraceptives). 
3. 
Signed informed consent form that meets all current ICH/FDA 
regulations. 
4. 
Patients with a clinical diagnosis of mild to severe plaque 
psoriasis of the scalp, defined by a Investigator's Global 
Assessment (IGA) score of at least 2 at baseline/randomization. 
5. 
Patient is in good general health as determined by physical examination. 
Exclusion Criteria 
1. 
Patients under 18 years of age. 
2. 
Females who are pregnant, lactating or likely to become pregnant during 
the study. 
3. 
Patients whose scalp psoriasis necessitates systemic or other concomitant 
topical therapies during the study (concomitant treatment of body 
psoriasis with over the counter topical products including emollients, is 
allowed). 
4. 
Patient has a scalp skin condition that would interfere with the diagnosis 
or assessment of plaque psoriasis of the scalp (e.g., seborrheic dermatitis, 
eczema, cutaneous T-cell lymphoma, or other forms of psoriasis 
including guttate, inverse, pustular or erythrodermic psoriasis). 
5. 
Presence of pigmentation, extensive scarring, pigmented lesions. or 
sunburn in the treatment areas that could interfere with the rating of 
efficacy parameters, including planned extensive exposure to sunlight 
during the study. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 9 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
6. 
History of psoriasis unresponsive to topical treatments. 
7. Current immunosuppression or history of organ transplant. 
8. Patients who have a history of or current diagnosis of glaucoma. 
9. 
Patients who have had surgery on the eyes or eyelids within 1 month 
before baseline or plan to have eye or eyelid surgery during the study. 
10. Patients with active infection (including but not limited to bacterial, 
fungal and viral infection) and/or open wounds on the entire head and 
neck area. 
11. Patients who have used the following on the scalp within 2 weeks before 
baseline: 
a. 
Topical cmticosteroids 
b. 
Topical anti-psoriatic medication (e.g., salicylic acid, anthralin, coal 
tar, calcipotriene, tazarotene) 
c. 
Topical retinoids 
d. 
Topical anti-inflammatory agents 
e. 
Medicated shampoos for scalp psoriasis (including tar shampoos) 
12. Patients who have used within 2 weeks before baseline: beta blockers, 
lithium preparations, anti-malarial agents or tanning booths. 
13. Patients who have used topical corticosteroids on the body within 2 
weeks before baseline. 
14. Use within six months before baseline of biologic treatment for psoriasis 
(e.g., infliximab, adalimumab, alefacept). 
15. Use within three months before baseline of: 1) chemotherapy or 2) 
radiation therapy. 
16. Use within one month before baseline of: 1) systemic steroids, 2) 
systemic 
antibiotics, 
3) 
systemic 
antipsonattc 
treatment 
(e.g., 
methotrexate, cyclosporine, hydroxyurea), 4) PUV A therapy, 5) UVB 
therapy or 6) prescription strength systemic anti-inflammatory agents. 
17. Use within two months before baseline of any immunosuppressive drugs 
(e.g., tacrolimus, pimecrolimus) or oral retinoids. 
18. Changed brands/types or frequency of use of routine hair care products 
(shampoo, conditioner, sprays etc.) within J 4 days before baseline, or 
intend to change during the study. 
J 9. Receipt of any drug as part of a research study within 30 days before 
dosing. 
20. 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 participant at undue risk by 
participation. 
21. Known or suspected severe renal insufficiency or severe hepatic 
7 I 5150 I 3 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page I 0 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
disorders or severe heart disease. 
22. History or current diagnosis or clinical signs and symptoms of Cushing's 
disease or Addison's disease or other disturbance in the HPA axis or 
adrenal function. 
23. History of allergy or hypersensitivity to desoximetasone or history of any 
drug hypersensitivity or intolerance that, in the Investigator's opinion, 
would compromise the safety of the patient or the study. 
24. Current evidence of drug abuse or history of drug abuse within 1 year 
before the first dose, including, in the opinion of the Investigator, history 
of alcohol abuse or active alcoholism. 
25. Inability to understand the protocol requirements, instructions, and study-
related restrictions, and the nature, scope, and possible consequences of 
the clinical study. 
26. Unlikely to comply with the protocol requirements, instructions, and 
study-related restrictions, such as uncooperative attitude, inability to 
return for follow-up visits, and improbability of completing the clinical 
study. 
27. The patient is a member of the investigational study staff or a member of 
the family of the investigational study staff. 
28. Previous patiicipation in this study. 
Efficacy Endpoint 
The primary efficacy endpoint is the propotiion of patients in each treatment 
group who are considered a Clinical Success at Day 29 ± 2, as defined by an 
IGA score of 0 (clear) or I (almost clear) with at least a 2 grades reduction 
from baseline at Day 29 ± 2. That is, at Day 29 ± 2, patients with an JGA 
score of 3 or 4 at baseline must achieve a score of 0 or 1 and patients with an 
IGA score of 2 at baseline must achieve a score of 0 to be considered a 
Clinical Success. 
Therapeutic 
Efficacy Analysis 
Superiority of the Test shampoo over the Vehicle shampoo at Day 29 ± 2 will 
be tested using a two-sided Cochran-Mantel-Haenszel (CMH) test, stratified 
by clinical site, at the 5% significance level. The primary analysis will be 
performed using an imputation method of analysis for missing data in the 
Intent-to-Treat (ITT) population. Patients discontinued because of lack of 
treatment effect will be included in the primary analysis as treatment failures. 
The following two sensitivity analyses will also be performed on the primary 
efficacy endpoint: 
1. 
Primary analysis will be performed also including patients without an 
assessment at Day 29 ± 2. Patients with missing data at Day 29 ± 2 will 
be considered clinical failures. 
2. 
Primary analysis will be performed also including patients without an 
assessment at Day 29 ± 2. Patients from the Vehicle group with missing 
71515013 Rev. 2 • May 3 I. 20 16• Taro Pharmaceuticals • Page II of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Safety Analysis 
Sample Size 
Determination 
data at Day 29 ± 2 will be treated as clinical successes and patients from 
the Test group with missing data at Day 29 ± 2 will be treated as clinical 
failures. 
Adverse events will be classified using standard MedORA terminology 
Version 18.1 or higher and summarized by treatment group. Summary tables 
comparing the type, date of onset, date of resolution, incidence, severity, 
Investigator's opinion of relationship to the study drug, action taken, and 
outcome will be prepared by treatment group. If sufficient data exist, adverse 
event frequencies will be compared between treatments using Fisher's exact 
test or a similar test. 
Concomitant medication use during the study will be tabulated by patient. 
Signs and symptoms of scalp psoriasis will not be considered adverse events, 
unless in the Investigator's opinion, they have increased in frequency and/or 
severity to such an extent that the Investigator/patient considers that it is in 
the patient's best interest to be dropped from continued participation in the 
study and given alternative therapy for their condition. 
Ocular discomfort, vital signs and skin assessments will be analyzed for both 
treatments. Ocular safety evaluations will be assessed at the discretion of the 
Investigator based on the findings of the HEENT examination performed at 
each visit along with the ocular discomfort symptoms repmted by the patient. 
Ocular discomfort will be assessed by subjects and reported to staff during 
clinic visits (Appendix D). 
The primary statistical analysis of interest is a comparison of clinical success, 
as defined by an IGA score of 0 (clear) or 1 (almost clear) with at least 2 
grades reduction from baseline at Day 29 ± 2, of the Test treatment, 
desoximetasone 0.25% shampoo, to the clinical success of the respective 
Vehicle shampoo in the ITT population. Based on results fl-om Taro's Phase 
II study 71342608 the clinical success of the Test formulation is expected to 
be approximately 27% for an application duration of 15 minutes. The clinical 
success of the Vehicle formulation is expected to be approximately 10% for 
the same application duration. Based on a two-sided, Yates' continuity-
corrected Z-test and a pooled response rate for the standard error of the 
difference in propmtions, 166 patients in the active group and 166 patients in 
the placebo group of the ITT population will provide at least 97% power to 
demonstrate superiority at the 5% significance level (p < 0.05) for the active 
treatment over placebo. To allow for about 10% of patients who may drop out 
from the study or arc otherwise non-evaluable, up to 370 patients may be 
enrolled ( 185 in the active group and 185 in the placebo group). 
71515013 Rev. 2 • May 31. 20 16• Taro Pharmaceuticals • Page 12 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
5.0 
STUDY SCHEMATIC 
Visit 1 
Visit 2 
Visit 3 
Day 
-1 to 1 
14± 2 
29±2 
Procedures 
Baseline/Rando 
Interim 
End of Study 
mizationt 
Visit 
Informed Consent 
X 
Medical History and 
X 
Baseline Demographics 
Inclusion/Exclusion 
X 
Physical Examination 
X 
X 
HEENT Examination 
X 
X 
X 
Vital Signs 
X 
X 
X 
Pregnancy Test* 
X 
X 
X 
Percent Scalp Affected 
X 
X 
X 
Investigator's Global 
X 
X 
X 
Assessment 
Skin Assessment 
X 
X 
X 
Ocular Discomfort 
X 
X 
Assessment 
Concomitant Medications 
X 
X 
X 
Weigh and Dispense 
X 
X 
Study Product 
Collect and Weigh Study 
X 
X 
Product 
Review/Provide Patient 
X 
X 
X 
Diary 
Adverse Events 
X 
X 
* Pregnancy test will be conducted for females of childbearing potential. 
t Patients should administer study product once daily for 28 days starting on Day I through Day 
28. The product will be left in place on the scalp for 15 minutes. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 13 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
6.0 
LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Term 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
BP 
Blood Pressure 
c 
Celsius 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
eCTD 
electronic Common Technical Document 
FDA 
Food and Drug Administration 
HEENT 
Head, Eyes, Ears, Nose, Throat 
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 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OHRP 
Office of Human Rights Protection 
OTC 
Over-the-Counter 
PAS! 
Psoriasis Area and Severity Index 
PGA 
Physician's Global Assessment 
PSSI 
Psoriasis Scalp Severity Index 
PUVA 
Psoralen and UltraViolet A 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
USA 
United States of America 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 14 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
7.0 
INTRODUCTION 
Taro Pharmaceuticals U.S.A., Inc. (Taro) plans to submit an Investigational New Drug 
Application (IND) for a new formulation of desoximetasone; desoximetasone 0.25% shampoo. 
This product contains a potent corticosteroid to be indicated for the treatment of plaque psoriasis 
in patients 12 years of age or older. 
7.1 
Disease Being Treated 
Psoriasis is an immune (T-cell)-mediated inflammatory skin disease that affects 
approximately 2% of the western population. 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 repmis 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 
At least 50% of all psoriasis cases have scalp psoriasis. Although head represents only 
10% of the whole body surface, the visibility and symptoms of scalp psoriasis can be 
seriously debilitating for many patients, inducing social and emotional distress and 
negatively impacting quality of life.4 Scalp psoriasis is more difficult to treat compared to 
psoriasis of the body, because the skin of the scalp is less accessible to topical treatments 
primarily because of the presence of hair. Moreover, vehicles used in psoriasis 
medications are often not cosmetically acceptable for scalp treatment, thereby negatively 
impacting treatment adherence. There is a need for effective, safe and cosmetically 
acceptable products for the treatment of scalp psoriasis to improve both compliance and 
response to treatment. 5 
Psoriasis severity is determined using various tools, the most extensively studied index 
being the Psoriasis Area and Severity Index (PASl), 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. Scalp psoriasis is often assessed using the 
Psoriasis Scalp Severity Index (PSSI) or the Physician's Global Assessment (PGA). 
However, the validity and sensitivity of such tools are not well characterized and still 
under investigation. Indicators for the effect of psoriasis on quality oflife and response to 
treatment often influence the overall severity of the disease. lienee, a clinically 
meaningful global assessment by the physician characterizing lesions on a 5-point scale is 
considered most appropriate and recommended by the FDA for the purpose of psoriasis 
clinical trials.
7 
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. Scalp psoriasis treatments 
715 15013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 15 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase I I I Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
historically include topical creams, sprays, lotions, foams, and the more recently 
introduced shampoos. Examples of marketed products include corticosteroids (Topicmi@, 
Clobex"'), Vitamin A and D derivatives (Tzorac@, Dovonex@), NSAlDs (salicylic acid), 
etc. For more severe cases, systemic therapy (methotrexate, oral retinoids, UV light, 
biologics, etc) may be warranted; however, the side effect profile ofthese products limits 
their use. 1'2'5'8' 9 
Desoximetasone is a high potency synthetic COiiicosteroid 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 Topicmi@ 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) 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. 10 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 .1'2'5'8'9 
Shampoos are considered a preferred treatment option for scalp psoriasis because of ease 
of application and cosmetic acceptability. There are many OTC coal tar shampoos in the 
market for treating mild scalp psoriasis. For the moderate-severe cases, a prescription 
shampoo containing potent corticosteroids is available in the market (Ciobex"' shampoo, 
clobetasol propionate, 0.05% ). 
A new formulation of desoximetasone - Desoximetasone Shampoo, 0.25% has been 
developed by Taro Pharmaceuticals U.S.A., Inc. (Taro), and is the Test product used in 
this study. 
7.3 
Scientific and Statistical Considerations 
This phase III study (DSXS 1536) has been designed based on review of multiple clinical 
studies in psoriasis, including Taro's phase II dose-ranging study on Desoximetasone 
Shampoo, 0.25% (DSXS 1411)
12 and those studies submitted as part of the NDA for 
currently marketed Taclonex@ (betamethasone and calcipotriene) scalp suspension (NDA 
Number: 22-185) 
13 and Clobex'" ( clobetasol propionate) shampoo, 0.05% (Gal derma 
Laboratories, NDA Number: 21-644). 
The FDA statistical review and analyses conducted for phase Ill studies for Taclonex'l<' 
(betamethasone and calcipotriene) scalp suspension, 
13 were used to select the patient 
population (patients with a clinical diagnosis of mild to severe plaque psoriasis of the 
scalp) and the definition of Clinical Success (Investigator's Global Assessment (IGA) of 
disease severity score ofO (clear) or I (almost clear) with at least a 2-grade improvement 
from baseline IGA at the end of the treatment) for this phase III study (DSXS 1536). The 
phase III studies for Clobex'" (clobetasol propionate) shampoo, 0.05% indicated a success 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 16 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase lll Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
rate of 44% in the active group and approximately 2% in the vehicle group after 4 weeks 
of treatment. 14 
Based on these NDA studies, previous communications with Sponsor, and pre-IND 
discussions regarding this study with the FDA (PIND# 118881 briefing package and 
FDA letter dated 9118/2013), a 28-day treatment period was considered appropriate to 
determine therapeutic efficacy of the Test shampoo formulation. 
Taro's phase II dose-ranging study on Desoximetasone Shampoo, 0.25% (DSXS 1411) 
was designed to evaluate therapeutic efficacy using multiple application durations of the 
product. The results of this phase II study were used to determine the appropriate 
duration of application (15 minutes) and the expected clinical success rate for subsequent 
phase III efficacy studies. Based on data from this study, a population of 370 patients, 
with up to 185 patients receiving Test treatment and up to 185 patients receiving Vehicle 
treatment, for an application time of 15 minutes was considered sufficient to demonstrate 
efficacy, safety and superiority to Placebo for the phase 1II study (DSXS 1536). 
The application time of 15 minutes was also supported based on results from Taro's in-
vitro study that used tape stripping and vertical Franz cells to investigate the deposition of 
desoximetasone from a shampoo formulation. 15 At 10 minutes following application, 2: 
99% of the applied dose was recovered on the skin surface and no quantifiable amounts 
of desoximetasone were detected in the receptor compartment or inside the skin. 
Therefore, application durations of< 15 minutes will not be used in the Phase 3 studies. 
Application durations of> 15 minutes are expected to reduce the patient's dosing 
compliance and are thus considered impractical for patient's daily routine. 
Desoximetasone is currently marketed by Taro as a gel (0.05%), cream (0.05% and 
0.25%) and ointment (0.05% and 0.25%) indicated for the relief of the inflammatory and 
pruritic manifestations of corticosteroid-responsive dermatoses, and as a spray (0.25%) 
indicated for the treatment of plaque psoriasis in patients 18 years of age or older. The 
new dosage form shampoo, the Test product for this study, was formulated with a highest 
marketed concentration (0.25%) to facilitate convenience by reducing contact time with 
the skin and to improve treatment compliance and efficacy. 
7.4 
.Justification for use of Vehicle Shampoo 
A Vehicle 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 that 
contains no active ingredient to treat scalp psoriasis. A sample size of 185 patients is the 
minimum number of patients that can be enrolled into the Vehicle group to ensure high 
statistical power (97% or more) to show a difference at p < 0.05 (two-sided) between the 
active treatment and Vehicle (according to a 1:1, Test: Vehicle randomization scheme). 
7.5 
Risks and Benefits 
The risks and benefits to patients enrolled in clinical research studies that include a 
vehicle treatment group must be carefully considered based on three main criteria, 
71515013 Rev. 2 • May 31, 2016• Taro Pharmaceuticals • Page 17 of48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
namely: the disease being treated, the availability, efficacy and safety of already 
approved therapies, and the scientific and statistical requirements of the desired outcome 
of the research study. The Office of Human Rights Protection (OHRP), a Division of the 
USA Federal Government's Depmtment of Health and Human Services, has issued a 
detailed guidebook to Institutional Review Boards (IRBs) that includes discussion on the 
use of placebo in clinical studies.
17 
Patients eligible for randomized treatment will have a 50% chance of receiving the 
Vehicle product. 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 Vehicle group. 
All patients enrolled in this study will receive the benefit of fi·ee 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. 
8.0 
STUDY OBJECTIVE 
The objective of this study is to evaluate the therapeutic efficacy and safety of desoximetasone 
0.25% shampoo (Taro Pharmaceuticals, U.S.A., Inc.) compared to a Vehicle shampoo (Taro 
Pharmaceuticals, U.S.A., Inc.) in patients with mild to severe scalp psoriasis. 
9.0 
INVESTIGATIONAL PLAN 
9.1 
Study Design and Plan Description 
This randomized, double-blind, vehicle-controlled, parallel-group multiple-site study is 
designed to evaluate the therapeutic efficacy and safety of the investigational product, 
desoximetasone 0.25% shampoo (Taro Pharmaceuticals, U.S.A.), for the treatment of 
mild to severe scalp psoriasis. 
Up to 370 eligible patients with scalp psoriasis that satisfy all eligibility criteria will be 
enrolled into the study at Visit I. Patients must be at least 18 years of age, in overall good 
health. They should have a current diagnosis of mild to severe scalp psoriasis with IGA 
score of at least 2. 
Patients who meet all inclusion/exclusion criteria will be randomized in a 1: I ratio (Test: 
Vehicle) at Visit I. At least 185 qualified patients will receive Test product and 185 
patients will receive Vehicle product. The product will be left in place on the scalp for 15 
minutes. 
At Visit 1, patients who meet all inclusion/exclusion criteria will be randomized in a 1:1 
ratio (Test: Vehicle) for 28 days of treatment: 
The study products are: 
• 
Test: Desoximetasone 0.25% Shampoo (Taro) 
• 
Vehicle: Test Vehicle Shampoo (Taro) 
7 I 5 I 50 I 3 Rev. 2 • May 3 I, 20 I 6• Taro Pharmaceuticals • Page I 8 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Patients in each randomized treatment group will apply product once daily, according to 
provided instructions, for a total of28 days starting on Day I. 
During the study patients will visit the clinical center for a total of 3 scheduled visits: 
• 
Visit 1 (Day -1 to 1): Randomization 
• 
Visit 2 (Day 14 ± 2): Interim Visit 
• 
Visit 3 (Day 29 ± 2): End of Study or Early Termination 
The primary efficacy endpoint is the proportion of patients in each treatment group who 
are considered a Clinical Success, as defined by an IGA score of 0 (clear) or 1 (almost 
clear) with at least a 2-grade improvement from baseline IGA at Day 29 ± 2. That is, at 
Day 29 ± 2, patients with an IGA score of 3 or 4 at baseline must achieve a score of 0 or 
I, patients with an IGA score of 2 at baseline must achieve a score of 0 to be considered a 
Clinical Success. The 5-point IGA score represents an overall severity of scalp psoriasis 
based on plaque elevation, scaling and erythema. Severity represented by a score of 0-4 is 
categorized as 'clear', 'minimal', 'mild', 'moderate' or 'severe'. Refer to Appendix A for 
IGA scoring. 
The safety profile of each treatment group will be evaluated by comparing adverse 
events, dermal and ocular discomfmt and vital signs obtained through the study duration. 
Ethical consideration related to this protocol and the use of human patients will be 
reviewed by an IRB. 
9.2 
Selection of Study Design 
This phase III study has been designed based on review of multiple clinical studies in 
psoriasis, including Taro's phase II dose-ranging study on Desoximetasone Shampoo, 
0.25% (DSXS 1411) 12 and those studies submitted as a part of the NDA for currently 
marketed Taclonex® (betamethasone and calcipotriene) scalp suspension (NDA Number: 
22-185) and Clobex® clobetasol propionate shampoo, 0.05% (NDA Number: 21-644), 
13• 
14 
and results of Taro's in-vitro study that used tape stripping and vertical Franz cells to 
investigate the deposition of desoximetasone from a shampoo formulation.
15 Based on 
these studies, previous communications with Sponsor, and pre-IND discussions with the 
FDA (PIND# 118881 ), a daily application of shampoo for 15 minutes for a 28-day 
treatment duration and a population of 370 patients (185 patients receiving active 
treatment and 185 patients receiving vehicle treatment) was considered appropriate to 
demonstrate therapeutic efficacy and safety of desoximetasone 0.25% shampoo (Taro) 
compared to a Vehicle shampoo. 
9.3 
Selection of Study Population 
9.3.1 
Inclusion Criteria 
I. 
Male or non-pregnant, non-lactating females 18 years of age and older. 
2. 
If female and of child-bearing potential. have a negative urine pregnancy test 
at the baseline/ randomization visit and prepared to abstain from sexual 
71515013 Rev. 2 • May 3 I, 20 16• Taro Pharmaceuticals • Page 19 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
intercourse or use a reliable method of contraception during the study (e.g., 
condom with spermicide, IUD, oral, injected, transdermal or implanted 
hormonal contraceptives). 
3. 
Signed informed consent form that meets all current ICH/FDA regulations. 
4. Patients with a clinical diagnosis of mild to severe plaque psoriasis of the 
scalp, defined by a Investigator's Global Assessment (IGA) score of at least 
2 at Screening. 
5. Patient is in good general health as determined by physical examination. 
9.3.2 
Exclusion Criteria 
1. 
Patients under 18 years of age. 
2. Females who are pregnant, lactating or likely to become pregnant during the 
study. 
3. Patients whose scalp psoriasis necessitates systemic or other concomitant 
topical therapies during the study (concomitant treatment of body psoriasis 
with over the counter topical products including emollients, is allowed). 
4. Patient has a scalp skin condition that would interfere with the diagnosis or 
assessment of plaque psoriasis of the scalp (e.g., seborrheic dermatitis, 
eczema, cutaneous T-celllymphoma, or other forms of psoriasis including 
guttate, inverse, pustular or erythrodermic psoriasis). 
5. Presence of pigmentation, extensive scarring, pigmented lesions, or sunburn 
in the treatment areas that could interfere with the rating of efficacy 
parameters, including planned extensive exposure to sunlight during the 
study. 
6. 
History of psoriasis unresponsive to topical treatments. 
7. Current immunosuppression or history of organ transplant. 
8. 
Patients who have a history of or current diagnosis of glaucoma. 
9. 
Patients who have had surgery on the eyes or eyelids within 1 month before 
baseline or plan to have eye or eyelid surgery during the study. 
10. Patients with active infection (including but not limited to bacterial, fungal 
and viral infection) and/or open wounds on the entire head and neck area. 
11. Patients who have used the following on the scalp within 2 weeks before 
baseline: 
a. 
Topical co11icosteroids 
b. 
Topical anti-psoriatic medication (e.g .. salicylic acid, anthralin, coal tar, 
calci potriene, tazarotene) 
71515013 Rev. 2 • May 3 1, 20 16• Taro Pharmaceuticals • Page 20 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
c. 
Topical retinoids 
d. 
Topical anti-inflammatory agents 
e. 
Medicated shampoos for scalp psoriasis (including tar shampoos) 
12. Patients who have used within 2 weeks before baseline: beta blockers, 
lithium preparations, anti-malarial agents or tanning booths. 
13. Patients who have used topical corticosteroids on the body within 2 weeks 
before baseline. 
14. Use within six months before baseline of biologic treatment for psoriasis 
(e.g., infliximab, adalimumab, alefacept). 
15. Use within three months before baseline of: 1) chemotherapy or 2) radiation 
therapy. 
16. Use within one month before baseline of: 1) systemic steroids, 2) systemic 
antibiotics, 3) systemic anti psoriatic treatment (e.g., methotrexate, 
cyclosporine, hydroxyurea), 4) PUVA therapy, 5) UVB therapy or 6) 
prescription strength systemic anti-inflammatory agents. 
17. Use within two months before baseline of any immunosuppressive drugs 
(e.g., tacrolimus, pimecrolimus) or oral retinoids. 
18. Changed brands/types or frequency of use of routine hair care products 
(shampoo, conditioner, sprays etc.) within 14 days before baseline, or intend 
to change during the study. 
19. Receipt of any drug as part of a research study within 30 days before dosing. 
20. 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 participant at undue risk by pmiicipation. 
21. Known or suspected severe renal insufficiency or severe hepatic disorders or 
severe heart disease. 
22. History or current diagnosis or clinical signs and symptoms of Cushing's 
disease or Addison's disease or other disturbance in the HPA axis or adrenal 
function. 
23. History of allergy or hypersensitivity to desoximetasone or history of any 
drug hypersensitivity or intolerance that, in the Investigator's opinion, would 
compromise the safety of the patient or the study. 
24. Current evidence of drug abuse or history of drug abuse within I year before 
the first dose, including, in the opinion of the Investigator, history of alcohol 
abuse or active alcoholism. 
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CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
25. Inability to understand the protocol requirements, instructions, and study-
related restrictions, and the nature, scope, and possible consequences of the 
clinical study. 
26. Unlikely to comply with the protocol requirements, instructions, and study-
related restrictions, such as uncooperative attitude, inability to return for 
follow-up visits, and improbability of completing the clinical study. 
27. The patient is a member of the investigational study staff or a member of the 
family of the investigational study staff. 
28. Previous patiicipation in this study. 
9.3.3 
Restrictions during the Study 
The following medications will not be allowed for the specified wash-out periods 
and throughout the study. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 22 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Restricted medication 
ExamQies (not comQrehensive) 
Wash out 
TopicortC!i' (desoximetasone 0.25%) 
Topical corticosteroids (on scalp or 
spray, Cortaid® (hydrocortisone 1% ), 
body), retinoids or anti-
Clobex® ( clobetasol 0.05%), Diprolene® 
2 weeks 
inflammatory agents (on scalp) 
( betamethasone 0.05%), retinol, 
diclofenac, etc. 
Psorcon® ointment/cream, Dovonex® 
Topical anti-psoriatic medication 
(calcipotriene), Tazorac® (tazarotene), 
Vectical® (calcitriol), salicylic acid, 
2 weeks 
(on scalp) 
anthralin, coal tar, etc., including 
medicated shampoos 
Beta blockers, lithium preparations, 
metoprolol, labetalol, Eskalith, Lithobid, 
anti-malarial agents or tanning 
quinine, etc. 
2 weeks 
booths 
Remicade® (infliximab), Enbrel® 
Biologic treatment for psoriasis 
(etanercept), Humira® (adalimumab), 
6 months 
etc. 
Chemotherapy 
3 months 
Radiation therapy 
Prednisone 
(The use of inhaled or intranasal 
Systemic corticosteroids 
corticosteroids up to 1 mg/day is 
Systemic antipsoriatic treatment 
acceptable provided the patient has been 
Systemic antibiotics 
on a stable dose for 2 weeks before 
PUV A therapy 
dosing and will remain on the stable 
4 weeks 
UVB therapy 
dose throughout the study) 
Prescription strength systemic anti-
methotrexate, cyclosporine, hydroxyurea 
inflammatory agents 
*aspirin for prophylactic use on a stable 
dose up to 325 mg per day is acceptable 
Systemic retinoids 
Soriatane'" (acitretin), lsotretinoin etc 
8 weeks 
Systemic immunosuppressive drugs 
tacrolimus. pimecrolimus 
8 weeks 
Concomitant treatment of body psonasis with over the counter topical products 
including emollients is allowed. Prescription-strength topical and systemic anti-
psoriatic treatments for body psoriasis will not be allowed during the study. In 
71515013 Rev. 2 • May 31. 20 16• Taro Pharmaceuticals • Page 23 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
addition, patients must have consistently used a single brand/type of hair care 
product (e.g., shampoo, conditioner, spray, etc.) for a minimum of 14 days prior 
to baseline. Patients will be asked continue using the same brand/type and 
frequency of use throughout the study. 
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. The clinical report will include all 
reasons for early withdrawals. 
All patients who administer at least one dose of randomized study product will be 
included in the safety analysis comparing the Test/ Vehicle products. Reasons for 
early termination may include the following: 
• 
Worsening signs/symptoms of scalp psoriasis 
• 
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 
• 
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 
their next visit study procedures. For early termination the Investigator shall fully 
document the reason for early termination. 
9.4 
Treatments 
The following treatments will be used in the study: 
• 
Test: Desoximetasone shampoo, 0.25% (Taro Pharmaceuticals, U.S.A., Inc.), 
applied once daily for 28 days 
• 
Vehicle: Test Vehicle shampoo (Taro Pharmaceuticals, U.S.A., Inc.), applied 
once daily for 28 days 
9.4.1 
Treatments Administration 
Patients will be provided with verbal and written instructions on how to 
administer study product. The study product is to be applied to psoriasis-affected 
areas of the dry seal p once a day. Patients are to move the hair away from the dry 
scalp so that one of the affected areas is exposed. A small amount of the study 
shampoo is to be applied directly to the affected area by gently squeezing the 
715 !50 13 Rev. 2 • May 31. 20 16• Taro Pharmaceuticals • Page 24 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
bottle. The shampoo is to be gently rubbed into the affected area. The same 
procedure is to be followed for other affected areas on the scalp. Patients will be 
instructed to use only enough to cover affected areas and avoid application to 
face, groin, armpits, lips or eyes. If during application the product comes in 
contact with the eyes or eyelids, patients will be instructed to rinse the area with 
abundant water immediately. Patients should not cover the head with a shower 
cap while the shampoo is on the scalp. The shampoo is to be left in place for 15 
minutes before adding water, lathering and rinsing hair and scalp completely. 
Patients will be instructed to begin dosing on the evening of enrollment or in the 
morning on the day following enrollment. Treatments are to be applied once 
daily at approximately the same time, on each day, for 28 days starting on Day 1. 
Patients should not apply more than 50 ml of study product per week. 
9.4.2 
Identity of Investigational Product 
The following products will be used in the study: 
• 
Test: 
Desoximetasone 
0.25% 
shampoo, 
manufactured 
by 
Taro 
Pharmaceuticals. 
• 
Placebo: Test Vehicle shampoo, manufactured by Taro Pharmaceuticals. 
Study products will be supplied in 120 ml bottles. 
All randomized study products will be blinded and packaged in blinded sealed 
boxes. Each bottle will be identified by a label bearing the Sponsor name, 
protocol number, randomization number, treatment duration, a statement that the 
study product is for Investigational Use Only, a place for patient initials and the 
date the bottle was dispensed. The study staff will dispense the study product 
bottle only to those patients identified by the Investigator. The study staff will 
instruct the patients on the use and return of study product. 
Individual bottles of study product will be packaged in blocks. The 
randomization will be generated in blocks of 4. Four (4) patients' worth of 
product (2 patients worth of Test product, 2 patients worth of Vehicle product), 
based on a I: 1 randomization ratio, will be packed into a larger box. This larger 
box will be designated "one block" of study product. Further details for 
randomization are provided in section 9.4.3. 
The study product 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 products are stored in a locked, secure location, with access limited to 
the Investigator and his/her designee(s). An accurate inventory of the study 
product will be maintained in accordance with federal regulations. Study product 
will be stored at controlled room temperature 15-30°C (59-86°F). 
715 I 5013 Rev. 2 • May 31. 20 16• Taro Pharmaceuticals • Page 25 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Once the site has been notified that they may do so, all unused study product and 
empty or partially used bottles of study product may be returned to the Sponsor 
or designee. 
9.4.3 
Method of Assigning Patients to Treatment Groups 
At Visit 1 eligible patients will be randomized to the study and assigned a 
randomization number. Patient numbers will consist of a 2-digit site number and 
4-digit randomization number. The 4-digit randomization numbers will be 
assigned in ascending order beginning with the lowest number at each study site. 
The study product will be packaged and blinded by an independent clinical 
packaging company. The randomization will be generated in blocks of 4 to 
accommodate the 1:1 randomization scheme (2 Test:2 Vehicle). 
Each eligible patient will receive 2 x 120 ml bottles of study product (Test or 
Vehicle). Patients will be randomized to a treatment group in a blinded fashion 
by assigning randomization numbers in ascending sequential order starting with 
the lowest available randomization number at each site. All patients randomized 
will be identified by initials, date of birth, and a unique six-digit patient number. 
A perforated two-pmi label will be attached to each of the small sized boxes of 
study product supplies. Both pieces of the label will include the following 
information: Protocol number, randomization number, dosing instructions, space 
for patient's initials, statement that the study product is for investigational use 
only, space for dispensing date and the Sponsor's name. One part of the label 
shall remain attached to the box. The other part will be removed prior to 
dispensing and attached to the patient source documents. In addition all patients 
will be provided with written instructions on how to use the study product. Prior 
to dispensing, study product will be weighed. 
9.4.4 
Study Blind 
The Investigator, staff at the study site and study monitors will be blinded to the 
patient assignment. Each study site will have at least one Independent Dispenser. 
The role of the Independent Dispenser is to dispense and collect all study product 
bottles from the patients and to ensure the study product logs are repmied 
correctly. They should not be involved in collecting any efficacy or safety data in 
the study, thus ensuring the integrity of the study blind. 
To ensure that information that could potentially bias handling of data is not 
disclosed, the clinical packaging company will hold the randomization scheme 
until release is requested by the Sponsor or designee. Unblinding code in the 
form of a scratch off portion of the product label attached to the source 
documents will be retained at the study site to be opened in case of medical 
emergency only. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 26 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Whenever possible, the Novum Medical Monitor must be contacted before 
breaking the blind for any patient. In the event the blind is broken for any reason 
Sponsor and Novum will be notified as soon as possible in writing of the details 
ofthe occurrence. 
The bottles used for both study products will be similar in size, shape and color. 
This will allow the treatment phase of the study to be conducted under double-
blind conditions, such that neither the patient nor the Investigator or study staff 
members will know the identity of each patient's treatment. 
9.4.5 
Compliance 
Patients will be considered compliant with dosing if they administered 75%-
125% of the required 28 doses and did not miss 4 or more consecutive doses and 
did not dose more than twice on any particular day. Compliance with dosing will 
be verified by the use of patient diaries. 
9.5 
Study Conduct 
9.5.1 
Visit 1 (Day -1 to 1) Baseline/Randomization [First day of application is Day 1] 
1. Informed Consent: Patients who are willing to comply with study procedures 
will read and sign the informed consent form. 
2. Medical History and Baseline Demographics: Patient's demographic and 
medical history including use of medications within the last 24 weeks will be 
reviewed. 
3. Inclusion/Exclusion Criteria: Patients will be screened for eligibility based on 
inclusion/exclusion criteria. 
4. Physical Examination: An overall assessment of health status will be conducted 
at the clinic. 
5. HEENT Examination: A general exam of the head, eyes, ears, nose and throat 
will be conducted at the clinic. 
6. Vital Signs: Pulse, blood pressure (BP), temperature and respiratory rate (RR) 
will be recorded. 
7. 
Pregnancy Test: A urine pregnancy test will be required of all female patients of 
childbearing potential before enrollment. 
8. 
Percent 
Scalp 
Affected: 
Patient's 
scalp 
will 
be 
examined 
by 
Investigator/designated clinician to determine the percent surface area affected 
with plaque psoriasis. Refer to Appendix C. 
9. 
Invcstigat01·'s Global Assessment (IGA): Patient's scalp will be examined to 
determine a psoriasis severity score based on a global assessment of plaques by 
the Investigator/designated clinician (refer to Appendix A). Patients with a score 
of2 or more, indicating mild-severe psoriasis will be included in the study. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 27 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
10. Skin Assessment: Skin irritation symptoms will be evaluated by an Investigator 
as a pm1 of baseline safety assessments and a score will be documented (refer to 
Appendix B). 
11. Weigh/Dispense Study Product: Study product bottle will be weighed and 
dispensed with dosing instructions. 
12. Review/Provide Diary: A dosing diary with instructions will be provided. 
13. Schedule Visit 2. 
9.5.3 
Visit 2 (Day 14 ± 2): Interim Visit 
1. HEENT Examination: A general exam of the head, eyes, ears, nose and 
throat will be conducted at the clinic. 
2. Vital Signs: Pulse, blood pressure (BP), temperature and respiratory rate 
(RR) will be recorded. 
3. Pregnancy Test: For women of childbearing potential, a urine pregnancy 
test will be performed to evaluate pregnancy. 
4. Percent 
Scalp 
Affected: 
Patient's 
scalp 
will 
be 
examined 
by 
Investigator/designated clinician to determine the percent surface area 
affected with plaque psoriasis. Refer to Appendix C. 
5. Investigator's Global Assessment (IGA): Patient's scalp will be examined 
to determine the psoriasis severity score based on a global assessment of 
plaques by the Investigator/designated clinician (refer to Appendix A). 
6. Skin and Ocular Assessments: Skin irritation symptoms will be evaluated 
by an Investigator and a score will be documented. Patients will also be 
questioned about any ocular discomfort as a part of safety assessments (refer 
to Appendices Band D). 
7. 
Collect/Weigh/Dispense Study Product: Study product bottle will be 
collected and weighed. A new bottle will be weighed and dispensed along 
with dosing instructions. 
8. Review/Provide Diary: Patient diary will 
be reviewed for dosing 
compliance. A new dosing diary with instructions will be provided. 
9. 
Concomitant Medications: Patients will be questioned about any new 
medications taken since last visit. 
I 0. Adverse Events: Patients will be questioned about any health status 
changes/adverse events since last visit. All events will be recorded. 
II. Schedule Visit 3. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 28 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
9.5.4 
Visit 3 (Day 29 ± 2): End of Study or Early Termination 
1. 
Physical Examination: An overall assessment of health status will be 
conducted at the clinic. 
2. 
HEENT Examination: A general exam of the head, eyes, ears, nose and 
throat will be conducted at the clinic. 
3. Vital Signs: Pulse, BP, temperature and RR will be recorded. 
4. Pregnancy Test: For women of childbearing potential, a urine pregnancy 
test will be performed to evaluate pregnancy. 
5. 
Percent 
Scalp 
Affected: 
Patient's 
scalp 
will 
Investigator/designated clinician to determine the 
affected with plaque psoriasis. (Refer to Appendix C). 
be 
examined 
by 
percent surface area 
6. 
Investigator's Global Assessment (IGA): Patient's scalp will be examined 
to determine the psoriasis severity score based on a global assessment of 
plaques by the Investigator/designated clinician (refer to Appendix A). 
7. 
Skin and Ocular Assessments: Skin irritation symptoms will be evaluated 
by an Investigator and a score will be documented. Patients will also be 
questioned about any ocular discomfort as a pmt of safety assessments (refer 
to Appendices B and D). 
8. 
Collect/Weigh Study Product: Study product bottle will be collected and 
weighed. 
9. 
Review Diary: Patient diary will be reviewed for dosing compliance. 
10. Concomitant Medications: Patients will be questioned about any new 
medications taken since last visit. 
11. Adverse Events: Patients will be questioned about any health status 
changes/adverse events since last visit. All events will be recorded. 
9.6 
Study Procedures 
9.6.1 
Informed Consent 
At Visit I, before any study related procedures, the study patient must sign the 
IRE-approved consent form. The consent form 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. 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 ce1tified translator. A copy of the ICF will be 
provided to the patient. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 29 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
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 
acute and chronic medical history and medical history relevant to their scalp 
psoriasis, as well as all medication use within the past 24 weeks. 
9.6.4 
Vital Signs 
The patient's vital signs will be recorded (pulse, blood pressure, temperature and 
respiration rate) at each clinic visit. 
9.6.5 
Physical Examination and HEENT Examination 
An overall assessment of health status will be conducted at Visits 1 and 3. A 
head, eye, ear, nose, throat (HEENT) examinations will be conducted at each 
clinic visit. 
Ocular safety evaluations will be assessed at the discretion of the Investigator 
based on the findings of the HEENT examination performed at each visit along 
with the ocular discomfort reported by the patient. Medical records associated 
with the ocular safety evaluation should be obtained for the study chm1. 
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 and 3. 
9.6.7 
Pregnancy Test 
All females of childbearing potential will have a urine pregnancy test performed 
at each specified clinic visit. The test must be negative at Visit 1 for the patient to 
be eligible for inclusion in the study. If the patient is of non-childbearing 
potential, then the source document must list the reason why she is of non-
childbearing potential (e.g., premenarchal). 
Any patient who becomes pregnant during the study must be discontinued and 
end of study procedures (Visit 3) completed. The outcome of the pregnancy 
should be followed by the Investigator to the conclusion of the pregnancy. 
9.6.8 
Dispensing Study Product 
An Independent Dispenser will weigh and dispense randomized study product 
bottle at Visits 1 and 2, with instructions on dosing. Patients will be instructed to 
begin dosing on the evening of enrollment or in the morning on the day following 
enrollment. The Independent Dispenser will ensure the study product logs are 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 30 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
reported correctly. They should not be involved in collecting any efficacy or 
safety data in the study, thus ensuring the integrity of the study blind. 
9.6.9 
Collecting Study Product 
Study product bottles will be collected at Visits 2 and 3 and weighed. 
9.6.10 Dosing Instructions and Diary 
Patients will be given a dosing diary at Visits 1 and 2 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 collected and reviewed at each subsequent visit by the study staff. 
9.6.11 Dosing Compliance 
Dosing compliance will be checked by site staff at Visits 2 and 3 by reviewing 
patient diary entries. Patients will be considered compliant with dosing if they 
administered 75%-125% of the required 28 doses and did not miss 4 or more 
consecutive doses and did not dose more than twice on any pmiicular day. 
9.6.12 Percent Scalp Affected 
Patient's scalp will be examined by Investigator/ designated clinician to 
determine the percent surface area affected with plaque psoriasis at all visits. At 
each subsequent visit, the % affected area will be monitored and documented. 
Refer to Appendix C. 18 
9.6.13 Investigator's Global Assessment (IGA) 
Patient's scalp will be examined to determine the psoriasis severity score based 
on a global assessment of plaques by the Investigator/designated clinician (refer 
to Appendix A). 
9.6.14 Skin Safety Assessments 
As a part of safety evaluation at each clinic visit, the Investigator/designated 
clinician will conduct an careful assessment of the scalp and adjacent skin (e.g., 
ears, forehead and neck) for local tolerability and a score will be documented 
(refer to Appendix B). 
9.6.15 Ocular Discomfort Assessment 
Ocular discomfort will be assessed by subjects and repoiied to clinic staff during 
scheduled visits (refer to Appendix D). If the shampoo comes into contact with 
the patient's eyes, the patient will be asked to report the contact at each visit. 
Ocular safety evaluations will be assessed at the discretion of the Investigator 
based on the findings ofthe HEENT exam performed at each visit along with the 
oculm' discomfmi reported by the patient. Medical records associated with the 
ocular safety evaluation should be obtained for the study chart. 
7 I 5 I 50 I 3 Rev. 2 • May 31, 20 I 6• Taro Pharmaceuticals • Page 3 I of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
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 MedORA (Version 18.1 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. In 
the opinion of the Investigator, if the patient suffers an AE that warrants discontinuation of 
the study drug due to 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. 
9.7.1 
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 inse1i/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. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 32 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
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. 
• 
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 product 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. 
71515013 Rev. 2 • May 31, 201 6• Taro Pharmaceuticals • Page 33 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase lli Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
• 
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 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: 
Or 
Gail Gongas 
Vice President, Clinical Trials 
Cell Phone 412-606-1603 
Phone 412-363-3300 x 522 
Fax412-291-3171 
Paolo Maria Fanzio, MD 
Medical Monitor 
Pittsburgh, PA 15206 
Phone: 412-363-3300 x597 
Fax: 412-924-0522 
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 Operation Coordinator, Clinical: 
Danielle Simpson 
Operation Coordinator. Clinical 
Phone: (914) 345-9001 x6234 
Email: Danielle.Simpson@Taro.com 
Taro Drug Safety Manager: 
Margo Lacy WyatL RN, BSN. 
Drug Safety Manager. Medical Affairs 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 34 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
Phone: 914-345-9001 Ext. 6758 
Email: Margo. Wyatt@taro.com 
and T AROPVUS@T ARO.com 
Investigators will be informed of any SAEs reported at other study sites within 
15 days from the initial report. 
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 statistical analysis of interest is a comparison of clinical success, as defined 
by an IGA score of 0 (clear) or 1 (almost clear) with at least 2 grades reduction from 
baseline at Day 29 ± 2, of the Test treatment, desoximetasone 0.25% shampoo, to the 
clinical success of the respective Vehicle shampoo in the ITT population. Based on 
results from Taro's Phase II study 71515008, the clinical success ofthe Test formulation 
is expected to be approximately 27% for an application duration of 15 minutes. The 
clinical success of the Vehicle formulation is expected to be approximately 10% for the 
same application duration. Based on a two-sided, Yates' continuity-corrected Z-test and a 
pooled response rate for the standard error of the difference in propmiions, 166 patients 
in the active group and 166 patients in the placebo group of the ITT population will 
provide at least 97% power to demonstrate superiority at the 5% significance level (p < 
0.05) for the active treatment over placebo. To allow for about 10% of patients who may 
drop out from the study or are otherwise non-evaluable, up to 370 patients may be 
enrolled (I 85 in the active group and 185 in the placebo group). 
10.3 
Study Populations 
1 0.3.1 Intent-to-Treat (ITT) Population 
The ITT population will include: 
• 
All randomized subjects. 
10.3.2 Safety Population 
• 
All patients who were randomized and applied at least one dose of the study 
product. 
71515013 Rev. 2 • May 3 I. 20 16• Taro Pharmaceuticals • Page 35 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
10.4 
Baseline Comparability 
Baseline comparability of each treatment group will be evaluated separately in the ITT 
and Safety populations. Comparative analyses will use appropriate statistical tests (e.g., 
one-way analysis of variance, Cochran-Mantei-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) 
• 
%Scalp affected 
• 
Number of months and/or years patient has suffered from symptoms caused by 
scalp psoriasis 
Descriptive statistics by treatment group will be presented. 
10.5 
Efficacy Endpoint 
The primary efficacy endpoint is the propotiion of patients in each treatment group who 
are considered a Clinical Success at Day 29 ± 2, as defined by an IGA score of 0 (clear) 
or 1 (almost clear) with at least a 2 grades reduction from baseline at Day 29 ± 2. That is, 
at Day 29 ± 2, patients with an IGA score of 3 or 4 at baseline must achieve a score of 0 
or 1 and patients with an IGA score of 2 at baseline must achieve a score of 0 to be 
considered a Clinical Success. 
10.6 
Efficacy Analysis 
10.6.1 Primary Analysis 
Superiority of the Test shampoo over the Vehicle shampoo at Day 29 ± 2 will be 
tested using a two-sided Cochran-Mantei-Haenszel (CMH) test, stratified by 
clinical site, at the 5% significance level. The primary analysis will be performed 
using an imputation method of analysis for missing data in the Intent-to-Treat 
(ITT) population. Details of the imputation method will be delineated in the SAP. 
Patients discontinued because of lack of treatment effect will be included in the 
primary analysis as treatment failures. 
10.6.2 Sensitivity Analyses 
The following two sensitivity analyses will also be performed on the primary 
efficacy endpoint: 
71515013 Rev. 2 • May 31. 20 16• Taro Pharmaceuticals • Page 36 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
1. 
Primary analysis will be performed also including patients without an 
assessment at Day 29 ± 2. Patients with missing data at Day 29 ± 2 will be 
considered clinical failures. 
2. 
Primary analysis will be performed also including patients without an 
assessment at Day 29 ± 2. Patients fi·om the Vehicle group with missing data 
at Day 29 ± 2 will be treated as clinical successes and patients from the Test 
group with missing data at Day 29 ± 2 will be treated as clinical failures. 
10.7 
Safety Analysis 
Adverse events will be classified using standard MedORA terminology Version 18.1 or 
higher and summarized by treatment group. Summary tables comparing the type, date of 
onset, date of resolution, incidence, severity, Investigator's opinion of relationship to the 
study drug, action taken, and outcome will be prepared by treatment group. If sufficient 
data exist, adverse event frequencies will be compared between treatments using Fisher's 
exact test or a similar test. 
Concomitant medication use during the study will be tabulated by patient. 
Signs and symptoms of scalp psoriasis wiii not be considered adverse events, unless in 
the Investigator's opinion, they have increased in fi·equency and/or severity to such an 
extent that the Investigator/patient considers that it is in the patient's best interest to be 
dropped from continued participation in the study and given alternative therapy for their 
condition. 
Ocular discomfort, vital signs and skin assessments wiii be analyzed for both treatments. 
Ocular safety evaluations will be assessed at the discretion of the Investigator based on 
the findings of the HEENT examination performed at each visit along with the ocular 
discomfot1 symptoms reported by the patient. Ocular discomfort will be assessed by 
subjects and reported to staff during clinic visits (Appendix D). 
11.0 
REGULATORY OBLIGATIONS 
11.1 
Institutional Review Board 
The study protocol, informed consent 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 stm1 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. 
71515013 Rev.:?. • May 31, 2016• Taro Pharmaceuticals • Page 37 of48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
as modified by the 64
111 World Medical Association General Assembly, October 2008. 
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 pa~iicipating 
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 
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 umque 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). All data 
and CRFs will be reviewed, evaluated and signed by the Investigator, as required. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 38 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
11.2.5 Drug Accountability 
All study product receipt, inventory, dispensing, dosing and reconciliation 
records will be maintained in compliance with Federal Regulations. The study 
product 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 product will be returned to Sponsor or designee. 
11.2.6 Drug Storage 
All study product will be stored at controlled room temperature 15-30°C (59-
860F), in a secure place with access by authorized individuals only. The 
Investigator will be responsible for maintaining accurate records of study product 
receipt, dispensing, and return. At the end of the study, all partially used and 
unused study product will be returned to Sponsor or designee. 
11.2. 7 Pregnancies 
Patients with a positive pregnancy test at Visit 1 will not be enrolled in the study. 
Patients who repmt that they have become pregnant during the study or have a 
positive pregnancy test at any clinic visit will be followed to completion of the 
pregnancy. The pregnancy will be repmted as an AE. 
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 ofbi1th control. Alternatively, any 
of the following methods of bi1th control are acceptable: oral contraceptives, 
contraceptive patches/implants (e.g., Skyla® and Mirena®), Depo-Provera®, 
double barrier methods (e.g., condom and spermicide) or IUD. Before study 
enrollment women of childbearing 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 each specified clinic visit 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. 
Reporting timelines and Novum/Sponsor contact will be consistent with SAE 
reporting guidelines (see section 9.8.2 of the protocol). i.e .. pregnancies will be 
reported to the Sponsor/Novum within 24 hours. 
715 15013 Rev. 2 • May 3 I, 20 16• Taro Pharmaceuticals • Page 39 of 48 


CONFIDENTIAL J>ROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
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 bi11h. 
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 
I. 
23 
causa 1ty. 
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 
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 ofthe study, a statistical rep011 including a description of the analysis 
performed, and other documentation as may be appropriate. The report will be in 
71515013 Rev. 2 • May 31, 2016• Taro Pharmaceuticals • Page 40 of48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
electronic format according to eCTD and ICH formatting standards and 
guidelines. 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. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 41 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
12.0 
REFERENCES 
www.psoriasis.org. 
2 
National Clinical Guideline Centre, U. Assessment and management of psoriasis. NCGC 
Guideline (20 12). 
3 
Jacob, S. Corticosteroid and Fragrance Allergy Exacerbating Scalp Psoriasis. J Clin Aesthet 
Dennato/7, 54-55 (2014). 
4 
Bucolo, S. Head and Neck Psoriasis. Psoriasis, Dr. Jennifer Soung (Ed.), ISBN: 978-953-307-
878-6, IntechOpen (2012). 
5 
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). 
6 
Feldman, S. R. & Krueger, G. G. Psoriasis assessment tools in clinical trials. Annals of the 
rheumatic diseases 64 Suppl2, ii65-68; discussion ii69-73, doi: 1 0.1136/ard.2004.031237 (2005). 
7 
Louden, B. A., Pearce, D. J., Lang, W. & Feldman, S. R. A Simplified Psoriasis Area Severity 
Index (SPAS!) for rating psoriasis severity in clinic patients. Dermatology onlinejournallO, 7 
(2004). 
8 
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 Gesellschafl =Journal of the German Society 
of Dermatology: JDDG 12,667-682, doi:10.1111/ddg.12396 (2014). 
9 
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. Br J Dermatol 
168,954-967, doi:l0.1111/bjd.12276 (2013). 
10 
Taro Pharmaceuticals. Package Insert for TOPICORT® (desoximetasone) Topical Spray, 0.25%. 
(2013). 
11 
Gal derma. Package Insert for Clobex 0.05% shampoo. (20 11 ). 
12 
Taro's phase II dose-ranging study on Desoximetasone Shampoo, 0.25% (DSXS 1411). 
13 
FDA. Statistical REVIEW AND EVALUATION for NDA22-185 (Taclonex® (betamethasone 
and calcipotriene) scalp suspension). 
14 
FDA. Summary Basis of Approval, NDA 21-644, Clobex shampoo, 0.05%. (2004). 
15 
Taro in-vitro study investigated the deposition of Desoximetasone from shampoo formulation 
using vertical Franz cells. 
16 
ICH. Choice of Control Group and Related Issues in Clinical Trials E 10. 20 July (2000). 
17 
Penslar. IRB Guidebook, Office for Human Rights Protection. US Department of Health and 
Human Services ( 1993 ). 
18 
Olsen, E. A. et al. Alopecia areata investigational assessment guidelines--Part II. National 
Alopecia Arcata Foundation. Journal of the American Academy ofDermatology 51, 440-447, 
doi: 10.1 016/j.jaad.2003.09.032 (2004). 
19 
FDA. 21 CFR 320 Procedures for Determining the Bioavailability or Bioequivalence of Drug 
Products. Department of Health and Human Services, Subchapter D-Drugsfor Human Use 5 
(2014). 
20 
FDA. 21 CFR Part 50 Protection of Human Subjects. Department ojHealth and Human Services, 
SuhchapterA-Generall (2014). 
21 
FDA. 21 CFR Part 56 Institutional Review Boards. Department ofHeulth and Human Services, 
Subchapter A-General! (2014). 
22 
World Medical Association Declaration of Helsinki: ethical principles for medical research 
involving human subjects. Jam a 310, 2191-2194. doi: 1 0. 1 001 /jama.20 13.281053 (20 13). 
23 
FDA. 21 CFR 312.32: IND Safety Reporting. (20 I 0). 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 42 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
24 
JCH. Structure and Content of Clinical Study Reports E3. Step 4 version. (1996). 
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CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
13.0 
APPENDICES 
13.1 
APPENDIX A 
Investigator's Global Assessment (IGA) of Disease Severity of Scalp Psoriasis 
Score 
Category 
Description 
0 
Clear 
Plaque elevation: no evidence of plaque elevation above normal skin level. 
Scaling: no evidence of scaling 
Erythema: no redness 
I 
Minimal 
Plaque elevation: very slight elevation above normal skin level, easier felt than 
seen 
Scaling: limited amount of very fine scales patiially 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 patiially 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. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 44 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
13.2 
APPENDIX B 
Skin Assessment (Forehead, Neck and Ears) 
At each clinic visit, the Investigator will evaluate the scalp and the adjacent skin (head, 
neck and ears) for irritation using the following scale: 
Dermal Response and Other Effects Scoring 
Dermal Response 
0 = no evidence of irritation 
1 =minimal erythema, barely perceptible 
2 =definite erythema, readily visible; minimal edema or minimal papular response 
3 = erythema and papules 
4 = definite edema 
5 = erythema, edema, and papules 
6 =vesicular eruption 
7 =strong reaction spreading beyond the application site 
Other Effects 
N =No other observations (numerical score= 0) 
A= Slightly glazed appearance (numerical score= 0) 
B =Marked glazed appearance (numerical score= I) 
C =Glazing with peeling and cracking (numerical score= 2) 
F =Glazing with fissures (numerical score= 3) 
G = Film of dried serous exudates covering all or pmi of the application site (numerical 
score= 3) 
H =Small petechial erosions and/or scabs (numerical score= 3) 
715 150 13 Rev. 2 • May 3 I, 20 16• Taro Pharmaceuticals • Page 45 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety of Desoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
13.3 
APPENDIX C 
Percent Scalp Affected-
18 
Investigators will use the following chart to identify areas and estimate scalp surface area 
affected by psoriasis plaques. 
LEFT SIDE: 18% 
RIGHT SIDE: 18% 
TOP:40% 
Ols<m/Canfield 
71515013 Rev. 2 • May 3 I. 20 16• Taro Pharmaceuticals • Page 46 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase III Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
13.4 
APPENDIX D 
Ocular Discomfort Assessment 
At Visits 2 and 3 the patient will be asked to assess if any ocular discomfort was 
experienced, YES or NO, since the last clinic visit. 
If YES is reported, the patient will be asked to repmi the signs and symptoms that apply 
from the list below or indicate any OTHER signs and symptoms experienced: 
Redness 
Itching 
Pain 
Swelling 
Burning 
Eye Discharge 
Stinging 
Blur (decrease in vision) 
Increased sensitivity 
Watery eyes 
Spots, flashes and floaters 
Foreign body sensation 
In addition, the patient will be asked to indicate if the shampoo came into contact with 
their eye, YES or NO, since the last clinic visit. If YES is reported, the patient will be 
asked to rate the discomfmi at the time of contact as None, Mild, Moderate or Severe. 
71515013 Rev. 2 • May 31, 20 16• Taro Pharmaceuticals • Page 47 of 48 


CONFIDENTIAL PROTOCOL 
A Randomized, Double-Blind, Vehicle-Controlled, Parallel-Design, Multiple-Site, Phase Ill Clinical Study to 
Evaluate the Efficacy and Safety ofDesoximetasone 0.25% Shampoo in Patients with Mild to Severe Scalp 
Psoriasis 
13.5 
APPENDIX E 
AMENDMENTS TO THE PROTOCOL 
Revisions to the protocol after initial IRB approval are summarized in the amendment below. 
Amendment 
I Date 
1 
1 2/24/2016 
The following revisions were made to the protocol dated 02/10/2016. 
• 
Removed Day 7 visit and adjusted visit numbers for Day 14 and Day 29 accordingly . 
References to all visit numbers were updated throughout the protocol to reflect this 3-visit 
schedule. 
• 
"None" added to Ocular Discomfort ratings . 
• 
Formatting and administrative changes throughout protocol. 
Amendment 
Date 
2 
5/31/2016 
The following revisions were made to the protocol dated 02/24/2016. 
• 
Primary endpoint definition revised per FDA advice letter for IND 124879 dated 04/07/2016. 
• 
Added language to clarify that CMH test will be stratified by clinical site. 
• 
Sample size determination wording and study power revised. 
• 
Revised primary analysis to use imputation method for missing data. 
• 
Added language to clarify when dosing should begin relative to randomization. 
• 
Study restrictions revised to allow OTC topical products for the treatment of body psoriasis. 
• 
Formatting and administrative corrections throughout the protocol. 
71515013 Rev. 2 • May 31, 2016• Taro Pharmaceuticals • Page 48 of48 

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