Clinical trial NCT03212963
Conditions: Plaque Psoriasis
Sponsor: Sun Pharmaceutical Industries Limited
Start date: 2017-03-21; Completion date: 2019-08-12
Enrollment: 16 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this open-label multicentric study is to determine the adrenal suppression potential and the pharmacokinetic (PK) properties of halobetasol lotion (HBP) applied twice daily for up to two weeks in subjects aged 12 to 16 years 11 months with stable plaque psoriasis. Subject enrollment will continue until at least 20 subjects with both screening and end of study (EOS) serum cortisol data (pre- and pos-tcosyntropin stimulation) have completed the study without any significant protocol violations (evaluable subjects). This may require the enrollment of approximately 25 subjects.

Detailed description:
This is an open label, multicenter study of an investigational formulation of HBP Lotion, 0.05% in male and female subjects aged 12 to 16 years 11 months with stable plaque psoriasis. Approximately 25 subjects with stable plaque psoriasis on at least 10% of their BSA (excluding the face, scalp, groin, axillae and other intertriginous areas), who fulfill the inclusion/exclusion criteria will be enrolled at multiple study sites. All subjects will have a screening CST to assess their HPA axis response at Visit 1 (Screening Visit).

Enrollment into the treatment phase of the study should be timed such that the screening CST will be performed a minimum of 20 days before Baseline Visit. At Visit 2 (Baseline), eligible subjects with normal adrenal function will be eligible to participate in the study.

Subjects will apply HBP Lotion, 0.05% to all psoriasis plaques identified at Visit 2 twice daily (approximately every 12 hours) for the assigned treatment period or until the investigator verifies the subject's psoriasis has cleared. The study is designed to determine the adrenal suppression potential and pharmacokinetic properties of the test article after the subject applies a maximum of approximately 50 grams per week for up to a two week treatment period. All subjects will have a CST to reassess their HPA axis response at EOS (or earlier if the investigator verifies the subject's psoriasis has cleared). In this study, an abnormal Hypothalamujs Pituitary Adrenal axis response to 0.25 milligram dose of cosyntropin is defined as a post-CST serum total cortisol level of less than equal to18 μg/dL.

Eligible subjects will have blood drawn at Screening for baseline drug concentration in plasma. On Day 8, all subjects, regardless of lesion clearance, will have blood drawn for assessment of trough drug concentration in plasma. At the Day 15 visit, subjects who have continued to treat lesions will have a final PK blood sample collected approximately 12 hours after their Day 14 evening application and just prior to the initiation of the CST.

Arms: arm 1: All subjects will receive Halobetasol Topical Lotion, 0.05%.
Interventions: intervention 1: Halobetasol Topical Lotion
Intervention descriptions: intervention 1: Halobetasol Lotion 0.05%, applied twice daily in subjects aged 12 to 16 years 11 months with stable plaque psoriasis.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
Page 1 of 72 
TI SOP 305-A Protocol Template, Version 06 
AN OPEN LABEL EVALUATION OF THE ADRENAL SUPPRESSION 
POTENTIAL AND PHARMACOKINETIC PROPERTIES OF TWICE DAILY 
HALOBETASOL PROPIONATE LOTION, 0.05% IN SUBJECTS  
12 TO 16 YEARS 11 MONTHS OF AGE WITH PLAQUE PSORIASIS 
RECEIVING TWO WEEKS OF TREATMENT 
 
PROTOCOL NUMBER: 
177-0551-201 
TI PROJECT NUMBER: 
177-0551-201 
IND NUMBER: 
 
ORIGINAL PROTOCOL:  
October 21, 2015 
AMENDMENT #1: 
November 4, 2015 
AMENDMENT #2: 
August 5, 2016 
FILENAME: 
177-0551-201_pro_05Aug2016_v3.0.docx 
SPONSOR: 
Sun Pharmaceutical Industries, Inc.  
(a Sun Pharma company)*  
 
SPONSOR REPRESENTATIVE: 
 
 
 
MEDICAL MONITOR: 
PROJECT MANAGER: 
The information contained in this document is confidential and proprietary 
property of Sun Pharmaceutical Industries, Inc. (a Sun Pharma company).  




Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 3 of 72 
TI SOP 305-A Protocol Template, Version 06 
STUDY ACKNOWLEDGEMENT 
I understand this protocol contains information that is confidential and proprietary to 
Sun Pharmaceutical Industries, Inc. (hereafter referred to as Sun Pharma), the Sponsor. 
 
I have read this protocol and agree that it contains all the details necessary to conduct 
the study as described. I will conduct this study following this protocol and will make a 
reasonable effort to complete the study in the time noted. 
 
I will provide the contents of this protocol to study staff under my direct supervision that 
need to know the contents to conduct the study. I will discuss this information with the 
study staff to ensure they are fully informed about the study and the test articles. I will 
provide the contents of the protocol to the responsible Institutional Review Board(s). 
These disclosures may be made; providing the contents are not used in any other clinical 
study and they are not disclosed to any other person or entity without prior written 
consent from Sun Pharma. This condition does not apply to disclosure required by 
government regulations or laws; however, I agree to give prompt notice to Sun Pharma 
of any such disclosure. 
 
I understand the study may be terminated or enrollment suspended at any time by Sun 
Pharma, with or without cause, or by me if it becomes necessary to protect the interests 
of the study subjects. 
 
Any additional information added to this protocol is also confidential and proprietary to 
Sun Pharma and must be treated in the same manner as the contents of this protocol. 
 
____________________________________ 
Printed Name of Principal Investigator 
 
____________________________________ 
 
_____________________ 
Investigator Signature  
 
 
 
 
Date 
 
Protocol number: 177-0551-201 
 
 
 
 
Site number:             
 
Version: 3.0 
 
Date of final version: August 5, 2016 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 4 of 72 
TI SOP 305-A Protocol Template, Version 06 
PROTOCOL SYNOPSIS 
Title 
An Open Label Evaluation of the Adrenal Suppression Potential and 
Pharmacokinetic Properties of Twice Daily Halobetasol Propionate Lotion, 
0.05% in Subjects 12 to 16 Years 11 Months of Age with Plaque Psoriasis 
Receiving Two Weeks of Treatment 
Study Type 
Phase 4 
Test Article 
Halobetasol propionate (HBP) Lotion, 0.05% 
Study Objective 
The objective of this study is to determine the adrenal suppression potential 
and the pharmacokinetic (PK) properties of HBP Lotion applied twice daily 
in subjects aged 12 to 16 years 11 months with stable plaque psoriasis.   
Study Design 
An open label, multicenter study. 
Treatment Groups 
All subjects will receive HBP Lotion, 0.05%. 
Duration of Treatment 
Up to two weeks. 
Duration of Study 
Participation in the study is a minimum of five weeks (at least 20 days 
between Screening and Baseline Visits, up to two weeks of treatment, and 
potential follow-up for any subjects who have evidence of hypothalamic-
pituitary-adrenal [HPA] axis suppression). 
Study Population 
Male and female subjects aged 12 to 16 years 11 months with stable plaque 
psoriasis. 
Total Number of 
Subjects 
Subject enrollment will continue until at least 20 subjects with both 
Screening and End of Study (EOS) serum cortisol data (pre- and post-
cosyntropin stimulation) have completed the study without any significant 
protocol violations (evaluable subjects). This may require the enrollment of 
approximately 25 subjects. 
Number of Sites 
Approximately four sites will participate in the study. 
Inclusion Criteria 
To enter the study, a subject must meet the following criteria:  
 
1. Subject is male or non-pregnant female 
 
  
2. Subject has provided written informed assent and was accompanied by 
the parent or legal guardian at the time of assent/consent signing. The 
parent or legal guardian has provided informed consent for the subject.  
3. Subject has a clinical diagnosis of stable plaque psoriasis involving a 
minimum of 10% body surface area (BSA)1 within the Treatment Area. 
 
 
                                                 
1 For this evaluation 1% BSA is approximately equivalent to the area of the subject’s closed hand (palm and 
fingers held together). 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 5 of 72 
TI SOP 305-A Protocol Template, Version 06 
4. Subject has an Investigator’s Global Assessment (IGA) score of at least 
three (3 = moderate) at the Baseline Visit. 
5. Subject is willing and able to apply the test article as directed, comply 
with study instructions and commit to all follow-up visits for the 
duration of the study. 
6. Females must have a negative urine pregnancy test (UPT)2 at the 
Screening (Part B) and Baseline Visits and agree to use an effective form 
of birth control3 for the duration of the study. 
Exclusion Criteria 
A subject is ineligible to enter the study if he/she meets one or more of the 
following criteria:  
 
1. Subject has spontaneously improving or rapidly deteriorating plaque 
psoriasis. 
2. Subject has guttate, pustular, erythrodermic or other non-plaque forms 
of psoriasis. 
3. Subject has a physical condition which, in the investigator’s opinion, 
might impair evaluation of plaque psoriasis, adrenal axis function (e.g., 
Addison’s Disease, Cushing’s Syndrome) or which exposes the subject 
to an unacceptable risk by study participation. 
4. Subject has used any phototherapy (including laser), photo-
chemotherapy or systemic psoriasis therapy including methotrexate, 
retinoids, cyclosporine or biologics within 30 days prior to the initiation 
of treatment with the test article. 
5. Subject has used systemic corticosteroids (including oral or 
intramuscular) or topical, inhaled or intranasal corticosteroids within 30 
or 14 days, respectively, prior to Part B of the Screening Visit and/or the 
subject has used systemic or topical corticosteroids between Part B of 
the Screening Visit and the initiation of treatment. 
6. Subject has had prolonged exposure to natural or artificial sources of 
ultraviolet radiation within 30 days prior to the initiation of treatment or 
is intending to have such exposure during the study that is thought by 
the investigator to likely modify the subject's disease. 
7. Subject has used topical psoriatic therapy including tar, anthralin, 
retinoids, vitamin D analogs (e.g., Dovonex®) within 14 days prior to 
the initiation of treatment with the test article. 
8. Subject has used emollients/moisturizers on areas to be treated within 
one day prior to the initiation of treatment with the test article. 
9. Subject is currently using lithium or Plaquenil (hydroxychloroquine). 
10. Subject is currently using a beta-blocking medication (e.g., propranolol) 
or angiotensin converting enzyme (ACE) inhibitors (e.g., lisinopril) at a 
dose that has not been stabilized, in the opinion of the investigator. 
                                                 
 
3 Effective forms of birth control include hormonal contraceptives [oral, injectable, transdermal or 
intravaginal] or intrauterine device (IUD) for two cycles (e.g., eight weeks) prior to test article application, 
condom and spermicidal or diaphragm and spermicidal). Other acceptable forms of birth control include: a) 
abstinence for subjects who are not sexually active or b) if the subject is in a monogamous relationship with 
a partner who is sterile (e.g., vasectomy performed at least six months prior to the subject’s initiation of 
treatment). Subjects who become sexually active or begin to have relations with a partner who is not sterile 
during the trial must agree to use an effective form of birth control for the duration of the study. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 6 of 72 
TI SOP 305-A Protocol Template, Version 06 
11. Subject has a history of sensitivity to any of the ingredients in the test 
article (see Section 6.1). 
12. Subject is pregnant, lactating, or is planning to become pregnant during 
the study. 
13. Subject is currently enrolled in an investigational drug or device study. 
14. Subject has used an investigational drug or investigational device 
treatment within 30 days prior to Visit 1 (Screening). 
15. Subject has been previously enrolled in this study and treated with the 
test article. 
16. Subject has an irregular sleep schedule or works night shifts (cortisol 
levels exhibit physiological diurnal variation). 
17. Subject has a screening Cosyntropin Stimulation Test (CST) with a post 
30-minute stimulation cortisol level of ≤ 18 µg/dL. 
18. Subject is known to be noncompliant or is unlikely to comply with the 
requirements of the study protocol (e.g., due to alcoholism, drug 
dependency, mental incapacity) in the opinion of the investigator.  
Study Procedures 
The following procedures will take place according to the visit schedule: 
 
Visit 1 (Screening Visit) (-Day 20 or longer): At Visit 1 (Screening Visit), 
study procedures will be explained by the study coordinator and the subject 
must provide written informed assent and be accompanied by the parent or 
legal guardian at the time of assent/consent signing. The parent or legal 
guardian must provide informed consent for the subject. Consent/assent must 
be signed prior to the initiation of any study-related procedures. At this visit, 
consenting/assenting subjects will have their medical history and 
Inclusion/Exclusion (I/E) criteria reviewed to determine subject eligibility. 
Subjects requiring a wash-out period will be asked to return to complete the 
following procedures of Screening Visit (Part B) once the wash-out is 
completed. All female subjects must have a negative UPT to be eligible for 
this study. Vital signs, height and weight, as well as IGA score, will be 
recorded. Subjects will have a Screening CST that should be initiated 
between 7 to 9AM to determine their adrenal system response. A Screening 
PK sample for drug concentration in plasma will be collected in all subjects 
in conjunction with the Screening CST. Enrollment into the treatment phase 
of the study (Baseline Visit) should be timed such that the Screening CST 
will be performed a minimum of 28 days before the projected end of the 
study phase. To accommodate this requirement, the Baseline Visit should 
ideally be scheduled at least 20 days after the Screening Visit. 
 
Visit 2 (Day 1/Baseline Visit): At Visit 2 (Day 1/Baseline Visit), subjects 
with a normal response to CST (post-stimulation serum cortisol > 18 µg/dL) 
and who continue to meet all the other I/E criteria will be enrolled in the 
study while subjects with significant abnormal screening results (particularly 
CST results; post-stimulation serum cortisol ≤ 18 µg/dL) will be 
discontinued as screen failures. All female subjects must have a negative 
UPT to continue in the study. A limited physical examination including vital 
signs and weight will be performed. IGA score will be recorded. Study staff 
will document percent BSA affected with disease and the percent BSA to be 
treated with the test article during the study at the Baseline Visit. Baseline 
local skin reactions (LSRs) will be recorded prior to test article application. 
All eligible subjects will apply the first dose in the clinic and be instructed 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 7 of 72 
TI SOP 305-A Protocol Template, Version 06 
to apply the assigned test article twice daily (approximately every 12 hours) 
to the psoriatic plaques designated by the investigator until Day 15. Each 
subject will be given a Subject Instruction Sheet and the study personnel will 
demonstrate how and where to dispense and apply test article to all the 
psoriatic plaques within the Treatment Area. The total dose of test article 
applied per week should be a maximum of approximately 50 grams/week. 
Any adverse events (AEs) or LSRs (i.e., burning/stinging only) post-
application will be recorded. A Subject Diary will also be given to each 
subject with completion instructions.   
 
Visit 3 (Day 8 ± 1): Subjects will return to the clinic on Day 8 for the study 
staff to record IGA score, percent BSA affected, review test article 
compliance, and collect information on AEs and LSRs. Prior to the Day 8 
visit, subjects will be requested to i) apply the test article at bedtime on Day 
7 and record the time, then ii) withhold application of the test article on the 
morning of the visit (Day 8).   
 
All subjects, regardless of lesion clearance, will have blood drawn on the 
morning of Day 8 to assess drug concentrations in plasma (trough values - 
~12 hours after previous dose). Any subject who has completely cleared their 
treated lesions (IGA score of 0 in Treatment Area) will discontinue dosing 
of test article, have a CST performed between 7 to 9AM, be assessed for any 
AEs and LSRs, review and document any concomitant medications, and 
complete EOS procedures on Day 8. If CST, AEs, LSRs, concomitant 
medications and EOS procedures cannot be performed on Day 8, then the 
subject will continue dosing of test article and return on Day 9 for CST and 
EOS procedures to be performed. Subjects who are clear at Day 8, complete 
CST on Day 8, and have all EOS procedures completed on Day 8 will exit 
the study at Day 8. 
 
Subjects who have not cleared by Day 8 will apply their morning dose at the 
clinic after the Day 8 trough blood sample is drawn and continue twice daily 
(approximately every 12 hours) application of the test article until Day 15. 
Their percent BSA to be treated will be documented at Day 8. Any AEs or 
LSRs (i.e., burning/stinging only) post-application will be recorded.   
 
Day 9 (Optional Visit): On the following day (Day 9), subjects cleared by 
Day 8 who could not have a CST and all EOS procedures performed on Day 
8 will have blood taken as part of their EOS CST, be assessed for any AEs 
and LSRs, documentation of any concomitant medications and complete all 
EOS procedures at Day 9 and will exit the study. 
 
Visit 4 (Day 15 ± 2 or EOS): Subjects who have continued to apply test 
article through Day 14 will return to the clinic for the study staff to collect 
information on AEs, LSRs, draw a final trough PK blood sample prior (~12 
hours following previous dose) to EOS CST, and perform the EOS CST. If 
any of these subjects have adrenal suppression (defined as post-CST cortisol 
level < 18 µg/dL), they will be scheduled for one or more post-treatment 
follow-up visits. Study staff will document IGA score and percent BSA 
affected with disease. All female subjects will have urine pregnancy testing. 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 8 of 72 
TI SOP 305-A Protocol Template, Version 06 
Post-Treatment Follow-up Visits (Suppressed Subjects Only): Any subjects 
who have evidence of adrenal suppression at EOS will return approximately 
every four weeks BUT no sooner than four weeks (28 days) after the EOS 
visit, and subsequently approximately every four weeks BUT no earlier than 
every four weeks (>28 days) thereafter for CST until the adrenal response 
returns to normal. Subjects with other ongoing AEs that require follow-up 
may also be followed per the discretion of the investigator. 
Study Measurements 
The following assessments will be performed: 
 
Investigator’s Global Assessment: 
At Screening, Baseline Visit/Day 1, Day 8, and Day 15/EOS, the overall 
severity of the subject’s psoriasis in the Treatment Area will be evaluated 
using the IGA score (5-point scale where 0 = clear, 1 = almost clear, 2 = 
mild, 3 = moderate, and 4 = severe). The IGA score is a static evaluation of 
the overall or “average” degree of severity taking into account all of the 
subject’s psoriatic lesions in the Treatment Area (excluding those on the 
face, scalp, groin, axillae and other intertriginous areas) by the investigator 
or designee. This evaluation takes into consideration the three individual 
characteristics of psoriasis (scaling, erythema and plaque elevation) with the 
IGA score at each visit representing the average of scaling, erythema or 
plaque elevation that is present amongst all of the lesions eligible for 
treatment. 
 
Percent BSA Affected with Disease: 
This is defined as the BSA which is affected with psoriasis within the 
Treatment Area. 
 
The 
percent BSA affected with psoriasis will be estimated at the Baseline 
Visit/Day 1, Day 8, and Day 15/EOS. 
 
Percent BSA Treated with Test Article: 
This is defined as the BSA which is affected with psoriasis within the 
Treatment Area that will be treated.
 
 
 
 
 
 The percent 
BSA to be treated with the test article will be estimated at Baseline and Day 
8.  
 
Test Article Compliance: 
Subjects will apply the first dose of test article to all plaques within the 
Treatment Area under staff supervision. At each visit, subject diaries will be 
reviewed to determine test article doses taken since the last visit and subjects 
will be counseled regarding compliance if necessary. Subjects will be 
instructed to record the date that the last dose was applied. All dispensed 
bottles of test article will be weighed at each visit and the amount of test 
article used will be recorded.   
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 9 of 72 
TI SOP 305-A Protocol Template, Version 06 
Local Skin Reactions: 
At each visit, subjects will be evaluated for the presence of any LSRs 
associated with the topical application of corticosteroids including 
telangiectasia, skin atrophy, burning/stinging, and folliculitis. 
 
Adverse Events: 
All AEs will be recorded. At each visit after the Baseline Visit, subjects will 
also be questioned specifically about the status of any ongoing AEs. 
 
 
 
 
Pharmacokinetic Assessment: 
Eligible subjects will have blood drawn at Screening for baseline drug 
concentration in plasma. On Day 8, all subjects, regardless of lesion 
clearance, will have blood drawn for assessment of trough drug 
concentration in plasma. At the Day 15 visit, subjects who have continued 
to treat lesions will have a final assessment of trough drug concentration in 
plasma approximately 12 hours after their Day 14 evening application and 
just prior to the initiation of the CST. 
Study Endpoints 
HPA Axis Response to Cosyntropin - Measurement of serum cortisol 
concentrations after stimulation of the adrenal cortex with cosyntropin 
(Cortrosyn® tests). HPA axis suppression is defined as a post-stimulation 
serum cortisol level < 18 µg/dL assessed at the end of study.  
 
Plasma Levels of HBP - Trough HBP concentrations in plasma will be 
assessed at Screening, Day 8 and Day 15/EOS approximately 12 hour post-
treatment.  
 
Other Safety Endpoints - AEs, LSRs, UPTs, dosing compliance, and extent 
of exposure. 
Sample Size 
Calculations 
No formal power calculations were performed to establish the sample size.  
The number of subjects enrolled who complete the study is historically 
consistent with other HPA studies. 
Statistical Methods 
All statistical analyses and summaries will be prepared using SAS® unless 
otherwise stated. All subjects enrolled in the study who were dispensed and 
applied test article at least once will be included in the analysis of safety and 
will be considered the Safety population. All enrolled subjects who applied 
at least one dose of test article and returned for at least one post-baseline visit 
will be considered the modified intent-to-treat (mITT) population.
 
 
 
 
 
 
 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 10 of 72 
TI SOP 305-A Protocol Template, Version 06 
Safety Analyses: 
Dosing Compliance 
Descriptive statistics will be used to summarize test article compliance for 
the mITT and the PK populations. Measures of test article compliance will 
include the duration of treatment (number of days dosed), the total number 
of applications (determined from the actual number of applications reported 
by the subject), and the percent of expected doses applied. A subject will be 
considered compliant with the dosing regimen if the subject applies at least 
80% but no more than 120% of the expected number of applications. 
 
Extent of Exposure 
The total amount of test article used (grams of test article applied) will be 
calculated from the weights of the returned test articles. Descriptive statistics 
(mean, median, standard deviation [SD], minimum and maximum) will be 
determined for the total amount of test article used by each subject in the 
mITT and PK populations. 
 
Urine Pregnancy Tests 
A listing of UPT results will also be prepared. 
 
Local Skin Reactions 
The frequency distributions of the severities of LSRs associated with topical 
application of corticosteroids including telangiectasia, skin atrophy, 
burning/stinging, and folliculitis will be summarized at Baseline and all 
follow-up visits. 
 
Adverse Events 
All subjects enrolled in the study who were dispensed and applied test article 
at least once will be included in the safety analyses (Safety population). All 
AEs reported during the study will be listed, documenting onset, whether 
therapy was required, any change in test article dosing, severity, possible 
relationship to test article, and outcome. Verbatim terms on the case report 
forms (CRFs) will be linked to preferred terms (PTs) and system organ class 
(SOC) using the Medical Dictionary for Regulatory Activities (MedDRA) 
mapping system. All reported AEs will be summarized by the number of 
subjects reporting AEs, SOC, PT, severity, and relationship to test article. 
 
HPA Axis Suppression Analysis 
HPA axis responses to CST will be dichotomized to normal and abnormal. 
 
 
 The mean increases in serum cortisol levels 
after stimulation will also be summarized at the end of study. In addition, 
descriptive statistics for the daily dose of test article will be tabulated 
separately for suppressed and non-suppressed subjects. Post-treatment 
follow up data will be summarized for subjects determined to have 
laboratory based evidence of adrenal suppression at the end of study or early 
termination visit. 
 
 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries, Inc.  Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 11 of 72 
TI SOP 305-A Protocol Template, Version 06 
Pharmacokinetic Analysis 
Trough HBP concentrations in plasma on Day 8 and Day 15 will be 
calculated and summarized.  






Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 14 of 72 
TI SOP 305-A Protocol Template, Version 06 
ABBREVIATIONS 
ACE 
Angiotensin Converting Enzyme 
ACTH 
Adrenocorticotropic Hormone 
AE 
Adverse Event 
AUCτ 
Area Under the Curve at Steady-State 
β-hCG 
Beta-human Chorionic Gonadotropin 
b.i.d. 
Twice a day 
BSA 
Body Surface Area 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
Peak Concentration 
CRF 
Case Report Form 
CST 
Cosyntropin Stimulation Test 
dL 
Deciliter 
EDC 
Electronic Data Capture 
EOS 
End of Study 
FDA 
Food and Drug Administration 
HBP 
Halobetasol Propionate 
HDPE 
High Density Polyethylene 
HPA 
Hypothalamic-Pituitary-Adrenal 
I/E 
Inclusion/Exclusion 
IGA 
Investigator’s Global Assessment 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
LSR 
Local Skin Reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
mIU 
Milli-International Units 
mL 
Milliliters 
µg 
Micrograms 
oz 
ounce 
PK 
Pharmacokinetic 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis Software 
SD 
Standard Deviation 
SOC 
System Organ Class 
TI 
Therapeutics, Incorporated 
Tmax 
Time to Peak Concentration 
UPT 
Urine Pregnancy Test 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 15 of 72 
TI SOP 305-A Protocol Template, Version 06 
USP 
United States Pharmacopeia 
VCA 
Vasoconstrictor Assay 
WHO 
World Health Organization 
 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 16 of 72 
TI SOP 305-A Protocol Template, Version 06 
TABLE OF CONTENTS 
Protocol Approval ............................................................................................................... 2 
Study Acknowledgement .................................................................................................... 3 
Protocol Synopsis................................................................................................................ 4 
Schedule of Events ............................................................................................................ 12 
Abbreviations .................................................................................................................... 14 
Table of Contents .............................................................................................................. 16 
1. 
Background ....................................................................................................... 19 
2. 
Rationale ........................................................................................................... 19 
3. 
Objective ........................................................................................................... 20 
4. 
Study Design ..................................................................................................... 20 
5. 
Study Population ............................................................................................... 20 
5.1 
Subject Eligibility ............................................................................................. 20 
5.1.1 
Inclusion Criteria ....................................................................................... 21 
5.1.2 
Exclusion Criteria ...................................................................................... 21 
5.1.3 
Subject Withdrawal Criteria ...................................................................... 22 
6. 
Test Articles and Regimen ................................................................................ 22 
6.1 
Description ........................................................................................................ 22 
6.2 
Instructions for Use and Application ................................................................ 23 
6.2.1 
Test Article Application ............................................................................ 23 
6.2.2 
Treatment Duration .................................................................................... 25 
6.2.3 
Dose Modifications .................................................................................... 25 
6.2.4 
Documentation of Compliance .................................................................. 25 
6.3 
Warnings, Precautions and Contraindications .................................................. 26 
7. 
Subject Number Assignment ............................................................................ 26 
8. 
Prior and Concomitant Therapies ..................................................................... 26 
8.1 
Prohibited Medications or Therapies ................................................................ 27 
8.2 
Allowed Medications or Therapies ................................................................... 27 
9. 
Study Procedures .............................................................................................. 28 
9.1 
Study Flow Chart .............................................................................................. 28 
10. 
Visit Activities .................................................................................................. 29 
10.1 
Visit 1 – Screening Visit (-Day 20 or Longer) ................................................. 29 
10.2 
Visit 2 (Day 1) Baseline .................................................................................... 30 
10.3 
Visit 3 (Day 8 ± 1) ............................................................................................ 31 
10.4 
Day 9 (Optional Visit) ...................................................................................... 33 
10.5 
Visit 4 (Day 15 ± 2) or End of Study ................................................................ 33 
10.6 
Post-Treatment Follow-Up Visits – Suppressed Subjects Only ....................... 34 
11. 
Clinical Evaluations .......................................................................................... 34 
11.1 
Investigator’s Global Assessment ..................................................................... 35 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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11.2 
Percent Body Surface Area Affected with Disease .......................................... 36 
11.3 
Percent Body Surface Area Treated with Test Article...................................... 36 
11.4 
Photography ...................................................................................................... 36 
12. 
Local Skin Reactions Associated with Topical Application of Corticosteroids36 
13. 
Laboratory Tests ............................................................................................... 37 
13.1 
Cosyntropin Stimulation Test ........................................................................... 37 
13.1.1 
Post-Treatment Follow-Up (only if suppressed at the End of Study) ....... 38 
13.2 
Pregnancy Tests ................................................................................................ 38 
13.3 
Pharmacokinetic Tests ...................................................................................... 39 
14. 
End of Study Criteria ........................................................................................ 39 
14.1 
Completion of the Study ................................................................................... 39 
14.2 
Subject Discontinuation .................................................................................... 39 
14.3 
Screen Failures .................................................................................................. 40 
14.4 
Study Termination ............................................................................................ 40 
15. 
Adverse Event Reporting .................................................................................. 40 
15.1 
Adverse Event ................................................................................................... 41 
15.2 
Serious Adverse Event ...................................................................................... 44 
15.3 
Pregnancy .......................................................................................................... 45 
16. 
Blinding/Unblinding ......................................................................................... 46 
17. 
Clinical Supplies ............................................................................................... 47 
17.1 
Test Article Information ................................................................................... 47 
17.2 
Supplies Provided by Therapeutics, Inc............................................................ 47 
17.3 
Supplies Provided by Investigator .................................................................... 47 
17.4 
Supplies Provided by the Clinical Laboratory .................................................. 47 
18. 
Statistical Considerations .................................................................................. 47 
18.1 
Sample Size ....................................................................................................... 47 
18.2 
Endpoints .......................................................................................................... 47 
18.2.1 
Efficacy Endpoints .................................................................................... 47 
18.2.2 
Safety Endpoints ........................................................................................ 48 
18.3 
Statistical Methods ............................................................................................ 48 
18.3.1 
Safety Analyses ......................................................................................... 49 
18.3.2 
HPA Axis Suppression Analyses .............................................................. 49 
18.3.3 
Pharmacokinetic Analyses ......................................................................... 50 
18.4 
Subgroup Analyses ........................................................................................... 50 
18.5 
Interim Analyses ............................................................................................... 50 
19. 
Ethical and Regulatory Considerations ............................................................. 50 
19.1 
Compliance with Good Clinical Research Practice .......................................... 50 
19.2 
Institutional Review Board and Informed Consent/Assent .............................. 50 
19.3 
Protocol Compliance ......................................................................................... 51 
19.4 
Protocol Revisions ............................................................................................ 51 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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19.5 
Study Monitoring .............................................................................................. 51 
19.6 
Case Report Form Requirements ...................................................................... 51 
19.7 
Reports to Institutional Review Board .............................................................. 52 
19.8 
Quality Assurance Audits ................................................................................. 52 
19.9 
Records Retention ............................................................................................. 52 
19.10 Record Confidentiality ...................................................................................... 53 
20. 
References ......................................................................................................... 54 
Appendix 1 
Sample Subject Instruction Sheet ............................................................. 55 
Appendix 2 
Sample Subject Diary ............................................................................... 58 
Appendix 3 
Test Article Information ........................................................................... 60 
A 3.1 
Test Article Packaging and Labeling ........................................................ 60 
A 3.2 
Test Article Storage and Preparation ........................................................ 60 
A 3.3 
Dispensing Test Article............................................................................. 60 
A 3.4 
Test Article Supply Records at Study Sites .............................................. 61 
A 3.5 
Dose Modifications ................................................................................... 61 
A 3.6 
Documentation of Application and Compliance....................................... 61 
A 3.7 
Return and Destruction of Test Article Supplies ...................................... 62 
Appendix 4 
Cosyntropin Package Insert ...................................................................... 63 
Appendix 5 
Protocol Amendments ............................................................................... 67 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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1. 
BACKGROUND 
Halobetasol propionate (HBP) is a well-known corticosteroid with anti-inflammatory 
properties. It is indicated for the local topical treatment of various inflammatory skin 
disorders (e.g., psoriasis). At present, there are three topical formulations of halobetasol 
propionate (Ultravate®) on the market – one is an ointment formulation, one is a cream 
formulation, and one is a lotion formulation, each containing 0.05% halobetasol 
propionate. Based on vasoconstrictor assay (VCA) studies, these formulations have been 
designated as Class I super-high potency corticosteroids (1).   
 
Systemic activity of topical corticosteroids depends on their absorption, metabolism, 
distribution, elimination and potency. The extent of the absorption of topically applied 
corticosteroids is dependent on structure and concentration of the corticosteroid, the 
vehicle used, duration and frequency of application, occlusion, condition of the skin and 
individual variation.  
 
Determination of plasma or serum cortisol concentrations before, during and after 
application of topical corticosteroid-containing formulations provides an indication of a 
suppression of the production of cortisol and provides more information than measurement 
of cortisol metabolites in urine. Measurement of plasma or serum cortisol concentrations 
after stimulation of the adrenal cortex with cosyntropin (Cortrosyn®) tests the ability of the 
HPA axis to react as a negative feedback mechanism (2, 3). Such “laboratory-based” 
adrenal suppression with different ointment and cream formulations containing 0.05% 
halobetasol propionate respectively, after one week of twice daily treatment, has been 
previously reported (4). More recently, a study was conducted to determine and compare 
the adrenal suppression potential and the pharmacokinetic (PK) properties of HBP Lotion, 
0.05% versus Ultravate® Cream applied twice daily in adult subjects with moderate to 
severe psoriasis (5). Results of this study support the safety of HBP Lotion, 0.05% with 
respect to adrenal suppressive effects and systemic exposure in adults with moderate to 
severe plaque psoriasis treated twice daily for up to two weeks. Of the 42 intent-to-treat 
subjects considered evaluable, only three (14.3%) Ultravate® Cream-treated subjects and 
five (23.8%) HBP Lotion-treated subjects demonstrated an abnormal HPA-Axis response 
at end of treatment. PK data from a subgroup of 24 subjects demonstrated systemic 
exposure to HBP from both treatments was similar as determined from peak concentration 
in plasma (Cmax), time to peak concentration (Tmax), and area under the curve over a dosing 
internal (AUCτ) at steady-state. 
2. 
RATIONALE 
Adrenal suppression effects of topical corticosteroids, especially super-high potency or 
Class I corticosteroids, are among the most important safety concerns for this group of 
products. This study is designed to determine the adrenal effects of the investigational 
lotion formulation of halobetasol propionate, 0.05% and characterize the steady-state 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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pharmacokinetics of the investigational lotion formulation in male and female subjects 
aged 12 to 16 years 11 months with stable plaque psoriasis.   
3. 
OBJECTIVE 
The objective of this study is to determine the adrenal suppression potential and the PK 
properties of an investigational lotion formulation of halobetasol propionate, 0.05% (HBP 
Lotion) applied twice daily in subjects aged 12 to 16 years 11 months with stable plaque 
psoriasis.   
4. 
STUDY DESIGN 
This is an open label, multicenter study of an investigational formulation of HBP Lotion, 
0.05% in male and female subjects aged 12 to 16 years 11 months with stable plaque 
psoriasis. Approximately 25 subjects with stable plaque psoriasis on at least 10% of their 
BSA (excluding the face, scalp, groin, axillae and other intertriginous areas), who fulfill 
the inclusion/exclusion criteria will be enrolled at multiple study sites. All subjects will 
have a screening CST to assess their HPA axis response at Visit 1 (Screening Visit). 
Enrollment into the treatment phase of the study should be timed such that the screening 
CST will be performed a minimum of 20 days before Baseline Visit. At Visit 2 (Baseline), 
eligible subjects with normal adrenal function will be eligible to participate in the study. 
 
Subjects will apply HBP Lotion, 0.05% to all psoriasis plaques identified at Visit 2 twice 
daily (approximately every 12 hours) for the assigned treatment period or until the 
investigator verifies the subject’s psoriasis has cleared. The study is designed to determine 
the adrenal suppression potential and pharmacokinetic properties of the test article after the 
subject applies a maximum of approximately 50 grams per week for up to a two week 
treatment period. All subjects will have a CST to reassess their HPA axis response at EOS 
(or earlier if the investigator verifies the subject’s psoriasis has cleared). In this study, an 
abnormal HPA axis response to 0.25 milligram dose of cosyntropin is defined as a post-
CST serum total cortisol level of ≤ 18 µg/dL. 
 
 
 
 
 
 
5. 
STUDY POPULATION 
5.1 
Subject Eligibility 
To be included in the study, subjects must meet the following inclusion and none of the 
exclusion criteria. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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5.1.1 Inclusion Criteria 
1. Subject is male or non-pregnant female 
  
2. Subject has provided written informed assent and was accompanied by the parent or 
legal guardian at the time of assent/consent signing. The parent or legal guardian has 
provided informed consent for the subject.  
3. Subject has a clinical diagnosis of stable plaque psoriasis involving a minimum of 10% 
BSA
 
 
4. Subject has an Investigator’s Global Assessment (IGA) score of at least three (3 = 
moderate) at the Baseline Visit. 
5. Subject is willing and able to apply the test article as directed, comply with study 
instructions and commit to all follow-up visits for the duration of the study. 
6. Females must have a negative urine pregnancy test (UPT)5 at the Screening (Part B) 
and Baseline Visits and agree to use an effective form of birth control6 for the duration 
of the study.  
5.1.2 Exclusion Criteria 
1. Subject has spontaneously improving or rapidly deteriorating plaque psoriasis. 
2. Subject has guttate, pustular, erythrodermic or other non-plaque forms of psoriasis. 
3. Subject has a physical condition which, in the investigator’s opinion, might impair 
evaluation of plaque psoriasis, adrenal axis function (e.g., Addison’s Disease, 
Cushing’s Syndrome) or which exposes the subject to an unacceptable risk by study 
participation. 
4. Subject has used any phototherapy (including laser), photo-chemotherapy or systemic 
psoriasis therapy including methotrexate, retinoids, cyclosporine or biologics within 30 
days prior to the initiation of treatment with the test article. 
5. Subject has used systemic corticosteroids (including oral or intramuscular) or topical, 
inhaled or intranasal corticosteroids within 30 or 14 days, respectively, prior to Part B 
of the Screening Visit and/or the subject has used systemic or topical corticosteroids 
between Part B of the Screening Visit and the initiation of treatment. 
6. Subject has had prolonged exposure to natural or artificial sources of ultraviolet 
radiation within 30 days prior to the initiation of treatment or is intending to have such 
                                                 
 
 
 
6 Effective forms of birth control include hormonal contraceptives [oral, injectable, transdermal or 
intravaginal] or intrauterine device (IUD) for two cycles (e.g., eight weeks) prior to test article application, 
condom and spermicidal or diaphragm and spermicidal). Other acceptable forms of birth control include: a) 
abstinence for subjects who are not sexually active or b) if the subject is in a monogamous relationship with 
a partner who is sterile (e.g., vasectomy performed at least six months prior to the subject’s initiation of 
treatment). Subjects who become sexually active or begin to have relations with a partner who is not sterile 
during the trial must agree to use an effective form of birth control for the duration of the study. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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exposure during the study that is thought by the investigator to likely modify the 
subject's disease. 
7. Subject has used topical psoriatic therapy including tar, anthralin, retinoids, vitamin D 
analogs (e.g., Dovonex®) within 14 days prior to the initiation of treatment with the test 
article. 
8. Subject has used emollients/moisturizers on areas to be treated within one day prior to 
the initiation of treatment with the test article. 
9. Subject is currently using lithium or Plaquenil (hydroxychloroquine). 
10. Subject is currently using a beta-blocking medication (e.g., propranolol) or angiotensin 
converting enzyme (ACE) inhibitors (e.g., lisinopril) at a dose that has not been 
stabilized, in the opinion of the investigator. 
11. Subject has a history of sensitivity to any of the ingredients in the test article (see 
Section 6.1). 
12. Subject is pregnant, lactating, or is planning to become pregnant during the study. 
13. Subject is currently enrolled in an investigational drug or device study. 
14. Subject has used an investigational drug or investigational device treatment within 30 
days prior to Visit 1 (Screening). 
15. Subject has been previously enrolled in this study and treated with the test article. 
16. Subject has an irregular sleep schedule or works night shifts (cortisol levels exhibit 
physiological diurnal variation). 
17. Subject has a screening Cosyntropin Stimulation Test (CST) with a post 30-minute 
stimulation cortisol level of ≤ 18 µg/dL. 
18. Subject is known to be noncompliant or is unlikely to comply with the requirements of 
the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the 
opinion of the investigator. 
5.1.3 Subject Withdrawal Criteria 
Procedures for handling subjects who are discontinued from the study are described in 
Section 14.2. Subjects who are discontinued will not be replaced; however, enrollment will 
continue until at least 20 evaluable subjects are achieved. 
6. 
TEST ARTICLES AND REGIMEN 
6.1 
Description 
Halobetasol Propionate Lotion, 0.05% (HBP Lotion) 
Active ingredient: 
Halobetasol propionate 
Other ingredients: 
 
 
 
  


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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6.2 
Instructions for Use and Application 
Subjects will apply a maximum of approximately 50 grams weekly of the HBP Lotion to 
affected areas designated by the investigator, twice daily (approximately every 12 hours) 
for up to two weeks. Subjects will be provided with an instruction sheet (refer to Appendix 
1) which includes detailed instructions for the application of test article.   
6.2.1 Test Article Application 
A study staff member will demonstrate how to dispense the test article and instruct the 
subject on the proper application of the test article to the affected areas at the Baseline 
Visit. 
 
All eligible subjects will apply the first dose in the clinic and be instructed to apply the 
assigned test article twice daily to the psoriatic plaques designated by the investigator until 
Day 15 or until the investigator verifies their psoriasis has cleared, whichever comes first. 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects should be instructed to wash their hands before and after each test article 
application. Instructions are as follows: 
 
The subject will be provided with instructions on how to apply the test article (see 
Appendix 1). The test article should be spread uniformly to cover the psoriatic lesions 
designated by the investigator within the Treatment Area.   
 
Subjects should apply the test article twice a day (approximately 12 hours apart) to all 
 
 
 
 
 
 
 
 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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As the subject’s plaques improve or worsen the amount of test article applied will likely 
decrease or increase, respectively.
 
 
 If the subject’s disease is too 
extensive to be reasonably managed with the approximately 50 grams per week limitation, 
then the subject should not be enrolled in the study or should be discontinued from the 
study. Lesions not treated with test article may be managed with emollient as detailed 
below. If the subject’s disease becomes unmanageable because of these limitations, he/she 
should be discontinued from the study.   
 
 
 
 
 
  
 
 
 
 
 
   
 
At Day 8, all subjects will return to the clinic for the study staff to record percent BSA 
affected, record percent BSA treated, IGA, review test article compliance, and collect 
information on AEs and LSRs. All subjects, regardless of lesion clearance, will have blood 
drawn on the morning of Day 8 to assess drug concentrations in plasma (trough values). 
Any subject who has completely cleared their treated lesions (IGA score of 0 in Treatment 
Area) will discontinue dosing of test article, have a CST performed between 7 and 9AM, 
be assessed for any AEs and LSRs, review and document any concomitant medications, 
and complete EOS procedures on Day 8. If CST, AEs, LSRs, concomitant medications and 
EOS procedures cannot be performed on Day 8, then the subject will continue dosing of 
test article and return on Day 9 for morning PK, CST and all EOS procedures to be 
performed. Subjects who are clear at Day 8, complete CST on Day 8, and have all EOS 
procedures completed on Day 8 will exit the study at Day 8. 
 
Subjects who have not cleared by Day 8 will apply their morning dose at the clinic after 
the Day 8 trough blood sample is drawn and continue twice-daily application of the test 
article until Day 15. Their percent BSA affected and percent BSA treated will be 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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documented at Day 8. Any AEs or LSRs (i.e., burning/stinging only) post-application will 
be recorded. 
 
Subjects will apply their final dose on the evening of Day 14 and record the time of the 
application. The final application of test article on Day 14 should be approximately 12 
hours before the final PK blood is drawn on the morning of Day 15.  
 
At Day 15, subjects who have continued to apply test article through Day 14 will return to 
the clinic for the study staff to collect information on AEs and LSRs, record percent BSA 
affected, draw a final trough PK blood sample prior to EOS CST, and perform the EOS 
CST. All units of test article will be collected and weighed. If any of these subjects have 
adrenal suppression
 they will be scheduled 
for one or more post-treatment follow-up visits.  
6.2.2 Treatment Duration 
The subject will apply the test article to all psoriasis plaques identified at Visit 2 (Baseline) 
in the Treatment Area, including any new lesions identified by the investigator that may 
develop in this area during the study, twice daily for two weeks or until the investigator 
verifies the subject’s psoriasis has cleared (see Section 10.3 for management of subjects 
that may clear prior to Day 15).
 
6.2.3 Dose Modifications 
The subject should not modify the treatment regimen without consultation with the 
investigator. In the event that the investigator believes dose modification is necessary 
(e.g., problems with tolerance) the subject’s care should be discussed with the Medical 
Monitor prior to making any dose modifications. All dose modifications must be reported 
on the appropriate Study Medication Compliance Form.   
6.2.4 Documentation of Compliance 
A Study Medication Compliance Form will be used to report the frequency of test article 
applications for each subject. The date of the first application of test article will be recorded 
on the CRFs. Any changes from the twice daily application specified in the protocol (e.g., 
missed applications, investigator directed reduction in application frequency) will also be 
recorded. The date of the last application of the test article will be recorded on the End of 
Study CRF. 
 
A Subject Diary will be dispensed to subjects to record the application time of all doses 
and to record any missed doses of the test article (see Appendix 2). Subjects will be 
instructed to bring the diary with them to each study visit. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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6.3 
Warnings, Precautions and Contraindications 
The test article is for topical use only. Care should be taken to avoid contact with eyes and 
all mucous membranes. If contact with eyes occurs, rinse thoroughly with water. Do not 
apply to face, scalp, groin, axillae and other intertriginous areas. 
 
Subjects with a known sensitivity to any of the ingredients in the test article should not 
participate in this study. 
 
Should skin irritation or rash develop, discontinue use. 
 
Subjects should not occlude the treated areas. 
 
In case of accidental ingestion, subjects should contact the investigator immediately. 
 
The effects of HBP Lotion, 0.05% in nursing mothers, pregnant women and their unborn 
children are unknown. Women of childbearing potential must not be pregnant or planning 
a pregnancy during the study period. 
7. 
SUBJECT NUMBER ASSIGNMENT 
Subjects who consent to participate in the study and meet the inclusion/exclusion criteria 
will be assigned a subject “screening” number at Visit 1. The screening number will consist 
of the two digit site number (e.g., “02-” in the following example) and an ascending two 
digit number, beginning with 01 that identifies the specific subject (for example, 02-01, 
02-02, etc.). This screening number will be used on the screening laboratory requisition 
forms and screening laboratory test results.  
 
Subjects who complete the screening phase of the study and are eligible for enrollment into 
the treatment phase of the study will be assigned a three digit (starting at 101 for Site 01, 
201 for Site 02, 301 for Site 03, etc.) subject number at Visit 2 (Baseline). Assignment of 
a subject number at each site will start with the lowest unassigned subject number assigned 
to a site and progress in sequential order. 
8. 
PRIOR AND CONCOMITANT THERAPIES 
Current medications and any medications taken in the 45 days prior to Visit 1 (Screening) 
will be recorded as prior/concomitant medications with the corresponding indication. The 
medications to be recorded include prescription and over-the-counter medications (except 
vitamins and dietary supplements). All medications taken on a regular basis should be 
recorded on the CRFs prior to commencing the use of the test article. 
 
Therapies (medication and non-medication therapies) not restricted by the protocol may be 
used during the study for the treatment or prevention of disease or to maintain good health. 
Vitamins and mineral supplements are permitted at dosages considered by the investigator 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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as reasonable for maintaining good health. Non-prohibited chronic therapies being used at 
Visit 1 may be continued. Any changes in concomitant therapies during the study must be 
recorded on the CRFs. The reason for any change in concomitant medications or 
therapies/procedures should be reported and should reflect either a baseline medical 
condition documented in the medical history of the CRF or an AE.  
8.1 
Prohibited Medications or Therapies 
Include medications within the following categories:  
• Topical or systemic medications intended to treat psoriasis including but not 
limited to those listed in Section 5.1.2 (e.g., retinoids, vitamin D analogs, 
anthralin, cyclosporine, and biologics). 
• Steroids – Systemic or topically administered, including inhaled or nasally 
administered treatments or ophthalmic preparations. This includes OTC topical 
steroid products (e.g., products containing 0.5% or 1% hydrocortisone). 
8.2 
Allowed Medications or Therapies 
Subjects may use an investigator-approved, medicated (non-steroid) shampoo to treat scalp 
psoriasis and the bland emollient to treat areas of psoriasis that are not treated with the test 
article. In the event that a bland emollient is used that is different than the product supplied 
by the Sponsor, the investigator must approve the use of this moisturizer to assure it meets 
protocol requirements as a bland moisturizer. 
 
For subjects who demonstrate adrenal suppression at the end of study, therapies that will 
not affect their adrenal function (e.g., topical tazarotene, emollients, etc.) may be used to 
treat their plaque psoriasis during the follow-up evaluation.  
 
All concomitant therapies, including the standard emollient and the investigator-approved 
shampoo must be recorded on the CRFs. All concomitant medications will be coded with 
the current version of the WHO Drug Dictionary. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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9. 
STUDY PROCEDURES 
9.1 
Study Flow Chart 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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10. 
VISIT ACTIVITIES 
Specific activities for each study visit are listed below. 
10.1 
Visit 1 – Screening Visit (-Day 20 or Longer) 
This visit should be scheduled between 7 and 8AM given the timing requirements for the 
study and the CST should be performed a minimum of 20 days before the Baseline Visit.   
 
PART A 
 
At this visit, the investigator or designee will: 
 
• Obtain a signed, written informed assent from the subject. The subject must be 
accompanied by the parent or legal guardian at the time of assent/consent signing. 
The parent or legal guardian must provide informed consent for the subject. 
Consent/assent must be signed prior to the initiation of any study-related 
procedures. 
• Assign each eligible subject a “screening” number. 
• Complete the Medical History and Demographics Form. 
• Review current medications and therapies. 
• Confirm the subject meets the inclusion/exclusion criteria.  
• Have the subject complete washout from any prohibited medications, if necessary. 
This may require that the subject return to the clinic to complete the remaining visit 
procedures. 
• Schedule the Visit for Part B; ideally at least 20 days prior to the Baseline (Day 1) 
Visit.  
 
PART B 
 
NOTE: Part B activities can be done concurrently with Part A if no washout period is 
required but should occur a minimum of 20 days prior to the Baseline (Day 1) Visit.   
 
At this visit, the investigator or designee will: 
 
• Perform a UPT for all female subjects; the results must be negative for the subject 
to participate in Part B of the screening phase. 
• Record changes to current concomitant medications and therapies. 
• Reconfirm the subject meets the inclusion/exclusion criteria.  
• Record vital signs, height and weight. 
• Record IGA score. 
• Perform a CST, see Section 13.1. CST should be initiated between 7 and 9AM at 
this visit. If the CST cannot be initiated before 9AM, another visit should be 
scheduled to complete Part B. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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• Draw blood for Baseline drug concentration in plasma. 
• Inform the subject that if the serum cortisol levels or CST results are not within the 
normal range, he/she will not be eligible for the study. 
• Schedule Visit 2 (Day 1/Baseline Visit). This visit should ideally be scheduled at 
least 20 days after completion of Visit 1, Part B. 
• Update the Subject Screening and Enrollment Log. 
10.2 
Visit 2 (Day 1) Baseline 
Prior to Visit 2, the investigator will review the subject’s Visit 1 CST results. Any subject 
with abnormal HPA axis function (see Section 13.1) will be considered a “screen failure” 
and will be discontinued from the screening phase of the study following the procedures in 
Section 14.3. Only subjects who meet all of the eligibility criteria (Sections 5.1.1 and 5.1.2) 
will be assigned a subject number for the treatment phase of the study.   
 
At this visit, the investigator or designee will: 
 
• Reconfirm medical history and demographics. 
• Perform a limited physical examination including vital signs and weight. 
• Reconfirm the subject meets the eligibility criteria, including CST results. Subjects 
must meet all the inclusion criteria and none of the exclusion criteria to be enrolled 
in the study.  
• Perform a UPT for all female subjects; the results must be negative for the subject 
to be enrolled. 
• Record any changes (including new medications) to current concomitant 
medications and therapies. 
• Record IGA score. 
• Document the percent BSA affected with disease. 
• Record the location and percent BSA of the plaques to be treated with the test article 
on a body diagram in the subject’s instruction sheet. 
• Query subject about the presence of any burning/stinging in the Treatment Area 
and examine them for the presence of any telangiectasia, skin atrophy, or folliculitis 
in the Treatment Area prior to test article application for Baseline assessment.   
• If the subject still meets the eligibility criteria, assign the subject the next available 
(lowest) subject number in ascending order. 
• Update the Subject Screening and Enrollment Log. 
• Dispense the initial and back-up units of test article as described in Appendix 3 
(Section A3.3). 
• Dispense standard (bland) emollient as required.  
 
NOTE: Standard (bland) emollient is to be used only on non-diseased skin or diseased 
skin not being treated with the test article as outlined in Section 6.2.1. Other 


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emollients should be avoided during the trial except with the approval of the 
investigator to assure they are a bland emollient.  
 
• Instruct the subject how and where to apply the initial dose of test article following 
the procedures in Section 6 and in Appendix 1. The first dose of test article will be 
applied in the clinic.   
• Document the percent BSA treated with test article. 
• Instruct the subject to apply the second dose of test article in the evening of the visit 
day and continue twice daily applications of the test article as instructed (see 
Section 6) to all psoriasis plaques identified within the Treatment Area identified 
at this visit.   
• Query subject about the presence of any burning/stinging in the Treatment Area 
post-application of the test article.   
• Identify an investigator-approved, medicated (non-steroid) shampoo the subject 
will use for treating scalp psoriasis only, if appropriate.  
• Dispense the Subject Instruction Sheet (Appendix 1) and the Subject Diary 
(Appendix 2) to the subject and provide instructions regarding how to complete the 
diary. 
• Remind the subject to record the time of the last application of test article in the 
Subject Diary the evening before (Day 7) the Visit 3 (Day 8) clinic visit and to NOT 
apply any test article on the morning of the Visit 3 (Day 8) clinic visit.   
• Schedule Visit 3 (Day 8 ± 1) – The timing of this visit should occur so that the 
trough PK blood draw on Day 8 occurs approximately 12 hours post-treatment on 
Day 7.  
10.3 
Visit 3 (Day 8 ± 1) 
For Visit 3 (Day 8 ± 1), the specific procedures performed will depend on whether the 
psoriatic lesions within the Treatment Area are completely clear or not.* Subjects will be 
requested to withhold application of the test article on the morning of the visit until after 
the trough PK blood draw has been taken. 
 
*NOTE: The site may want to schedule all subjects between 7 to 8AM or call the subject 
the day before the visit to see if their Visit 3 appointment needs to be adjusted to the earlier 
time window because it appears their disease may have cleared. 
 
At this visit, the investigator or designee will: 
 
• Observe/query the subject about any changes in his/her health since the previous 
study visit and specifically about LSRs associated with topical application of the 
test article (see Section 12). Initiate/update the appropriate adverse event form as 
required.  
• Review the subject’s compliance with the study requirements. 


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• Query the subject about any changes in concomitant therapies (including the 
standard emollient and the investigator-approved medicated shampoo as 
appropriate) since the previous study visit and document the findings. 
• Record IGA score. A subject’s plaque psoriasis is defined as cleared if the 
investigator reports a grade of 0 for IGA per Section 11 of the protocol. 
• Document the percent BSA affected with disease. 
• Withhold AM application of test article until after trough PK blood draw. 
• Draw blood to assess drug concentration in plasma (trough value).  
• For subjects that have cleared completely:7 
o Perform CST between 7 to 9AM as per Section 13.1 and complete the End 
of Study Form unless their CST test reveals adrenal suppression. If a subject 
has an abnormal HPA axis function, report as an adverse event and follow 
the subject approximately every four weeks as described in Sections 10.6 
and 13.1.1. 
o Perform a UPT for all female subjects. 
o Collect the Subject Diary and update the subject’s Study Medication 
Compliance Form CRF with dates of missed doses, if applicable. 
o Collect and weigh all units of test article and record the final weights in the 
CRF. No further treatment will be applied.8 
• For subjects that have not cleared: 
o Document the percent BSA to be treated with test article 
o Apply the AM dose at the clinic after the trough PK blood draw. 
o Collect used test article after the morning application (including weights) 
and re-dispense test article as necessary.   
o Instruct subjects to continue twice daily application and diary activities 
through the evening of the day prior (Day 14) to the next clinic visit (Day 
15) and remind the subject: 
1) to record the time of the last application of test article in the Subject 
Diary the evening before (Day 14) the Visit 4 (Day 15) clinic visit 
and, 
2) to NOT apply any test article on the morning of the Visit 4 (Day 15) 
clinic visit.  
o Query subject about the presence of any burning/stinging in the Treatment 
Area post-application of the test article.   
o Schedule Visit 4 (Day 15 ± 2) – The timing of this visit should occur so that 
the trough PK blood draw on Day 15 occurs approximately 12 hours post-
treatment on Day 14. 
                                                 
7 For subjects clear at Day 8, the end of study procedures may be done the following day on Day 9 if they 
cannot be completed on Day 8. 
8 If the subject has to return on Day 9 to complete end of study procedures then the subject will continue to 
dose on Day 8 (AM & PM dosing). The Day 9 visit must occur the day immediately after the Day 8 visit. 


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o Schedule the end of study visit (Day 15) for the morning so that the CST 
will occur at the same time (± one hour) as the CST performed at Visit 1 
(Screening). If possible, the CST should be initiated between 7 and 9AM.   
10.4 
Day 9 (Optional Visit) 
Subjects who cleared by Day 8 and could not have a CST and all EOS procedures 
performed on Day 8 will continue application of test article that evening and return the 
following day (Day 9) to have blood taken as part of their trough PK and EOS CST, be 
assessed for any AEs, documentation of any concomitant medications and complete all 
EOS procedures. These subjects will then exit the study at this visit. 
10.5 
Visit 4 (Day 15 ± 2) or End of Study 
These activities may occur as scheduled at the end of the assigned treatment period (15 
days) or earlier for subjects if the investigator verifies the subject’s psoriasis has cleared as 
defined per protocol (Visit 3, Day 8).   
 
This visit should occur so that the CST is initiated at approximately the same time (± one 
hour) as the CST performed at Visit 1 (Screening).   
 
At this visit, the investigator or designee will:  
 
• Observe/query the subject about any changes in his/her health since the previous 
study visit and specifically about LSRs associated with topical application of the 
test article (see Section 12). Initiate/update the appropriate adverse event form as 
required.  
• Review the subject’s compliance with the study requirements.  
• Query the subject about any changes in concomitant therapies (including the 
standard emollient and the investigator-approved medicated shampoo as 
appropriate) since the previous study visit and document the findings. 
• Document the percent BSA affected with disease. 
• Record IGA score.  
• Perform a UPT for all female subjects. 
• Collect the final blood sample for drug concentration in plasma just prior to the 
initiation of the CST.   
• Perform a CST (see Section 13.1).  
• After review of serum cortisol levels, complete the End of Study Form, unless the 
subject has an abnormal HPA axis response, then follow the procedures in Section 
13.1.1. 
• Collect and weigh all units of test article and record the final weights in the CRF. 
 


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If the end of study period CST results show a subject has an abnormal HPA axis function, 
report as an adverse event and follow the subject approximately every four (4) weeks as 
described in Sections 10.6 and 13.1.1. 
10.6 
Post-Treatment Follow-Up Visits – Suppressed Subjects Only 
These visits are only required for subjects who have demonstrated abnormal CST 
consistent with suppression at the end of study and are returning for the follow-up CST as 
per Section 13.1.1. Subjects with other ongoing AEs that require follow-up may also be 
followed per the discretion of the investigator. 
 
At this visit, the investigator or designee will:  
 
• Observe/query the subject about any changes in his/her health since the previous 
study visit. Initiate/update the appropriate adverse event form as required.  
• Query the subject about any changes in concomitant therapies (including the 
standard emollient and the investigator-approved medicated shampoo as 
appropriate) since the previous study visit and document the findings. Ensure that 
any concomitant medications are not prohibited (see Section 8.1). 
• Perform the CST. This test should be initiated at approximately the same time (± 
one hour) as the CST performed at Screening and if possible, the CST should be 
initiated between 7 and 9AM (see Section 13.1).   
• Complete the End of Study Form after review of the serum cortisol levels unless 
the subject has an abnormal HPA axis response, then follow the procedures in 
Sections 13.1 and 13.1.1.   
• Notify the subject if he/she needs to return to the clinic if the result is abnormal. 
Repeat CST will be performed approximately every four (4) weeks until adrenal 
axis function has been documented to return to normal. 
11. 
CLINICAL EVALUATIONS 
The following clinical evaluations will be performed according to the schedules indicated 
during the study. The same investigator should complete the evaluations for a given subject 
throughout the study. If this becomes impossible a sub-investigator with overlapping 
experience with the subject and the study should complete the evaluations. 
 
 
 
 
 
 
 
 


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11.1 
Investigator’s Global Assessment 
The IGA score (5-point scale of 0 to 4) is an evaluation of the overall severity of a subject’s 
psoriasis in the Treatment Area and takes into consideration the three individual 
characteristics of psoriasis (scaling, erythema and plaque elevation).  
 
The investigator should NOT refer to any other assessments to assist with this evaluation. 
This evaluation is NOT a comparison with the IGA at any other visit. The test article should 
not be applied within eight (8) hours prior to the scheduled clinic visit. At Screening, 
Baseline Visit/Day 1, Day 8, and Day 15/EOS, the investigator will evaluate all active 
psoriasis plaques that are in the Treatment Area and report the single integer score that 
describes the overall severity of the subject’s psoriasis using the following scale: 


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11.2 
Percent Body Surface Area Affected with Disease 
This is defined as the BSA which is affected with psoriasis within the Treatment Area.
 
 
he percent BSA affected with psoriasis will be estimated at 
the Baseline Visit/Day 1, Day 8, and Day 15/EOS. The investigator may use the estimate 
that 1% BSA is equivalent to the area of the subject’s closed hand (palm with fingers held 
together).  
11.3 
Percent Body Surface Area Treated with Test Article 
This is defined as the BSA which is affected with psoriasis within the Treatment Area that 
will be treated. 
 
 
 
 
 The percent BSA to be treated will be estimated at Baseline and Day 8. 
11.4 
Photography 
Photography documentation is not required in this study. However, during the study, the 
investigator may photograph areas of diseased skin of the subject per his/her discretion for 
informational purposes only (e.g., documentation of adverse event, etc.). These 
photographs will not be used for grading or any other similar study-related purpose. 
12. 
LOCAL 
SKIN 
REACTIONS 
ASSOCIATED 
WITH 
TOPICAL 
APPLICATION OF CORTICOSTEROIDS 
At all post-screening visits, the investigator or designee will observe or directly query the 
subject regarding local skin reactions known to be associated with topical application of 
corticosteroids. The severity of the following local skin reactions: telangiectasia, skin 
atrophy, burning/stinging and folliculitis will be recorded as none, mild, moderate, or 
severe. A LSR is to be recorded as an adverse event only if therapy or discontinuation of 
test article is required. 


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13. 
LABORATORY TESTS 
13.1 
Cosyntropin Stimulation Test 
At Visit 1 (Screening Visit, Part B), a cosyntropin stimulation test will be initiated for each 
subject between 7 and 9AM.   
 
At the End of Study visit (i.e., the visit at which psoriasis has cleared or end of the assigned 
treatment period), a CST (and any follow-up CSTs) should be ideally initiated between 7 
and 9AM but within ± one hour of the screening CST, after confirmation that the subject 
has not applied test article at least 8 hours prior to the visit.9 If these conditions are not met, 
the subject should be rescheduled for CST on the next day.  
 
Perform the cosyntropin stimulation test as follows: 
• Collect a pre-stimulation blood sample (approximately 6-7 mL) as specified in the 
Laboratory Manual. 
• Reconstitute one vial of cosyntropin (0.25 milligrams) in sodium chloride for 
injection USP (the volume of sodium chloride in the package insert for Cortrosyn 
[Appendix 4] is 2 to 5 mL). 
• Inject the cosyntropin intravenously (the length of time during which the 
cosyntropin should be injected is 2 minutes [Appendix 4]). 
• Thirty minutes after completing the cosyntropin injection collect a post-stimulation 
blood sample (approximately 6-7 mL) as specified in the Laboratory Manual. 
 
If the results of the Visit 1 (Screening) CST indicate the subject has an abnormal HPA axis 
response 
 the subject 
should be classified as a screen failure and withdrawn from the study following the 
procedures in Section 14.3. In addition, direct the subject to consult with their physician 
concerning the abnormality unless the investigator believes it is not medically indicated. 
The conversation with the subject must be documented in the source documents.  
 
If a subject’s end of study CST results show an abnormal HPA axis response 
 
 the test article will be considered to 
have caused adrenal suppression in the subject. Report this abnormality (ACTH stimulation 
test abnormal) as an AE. Instruct the subject not to use ANY topical or systemic steroids; 
however, other therapies that will not affect their adrenal function may be used to treat their 
plaque psoriasis. The subject should be scheduled to return for a follow-up visit no less 
than four (4) weeks after the end of study laboratory samples are collected (see Section 
13.1.1). In the event the subject is still found to have laboratory evidence of adrenal 
suppression, the subject will be required to return for additional follow-up visits, no less 
than every four (4) weeks, until the HPA axis response has been documented to return to 
                                                 
9 Site may wish to contact subject a day or so prior to the scheduled visit to confirm visit time and remind 
subject not to apply test article within eight (8) hours of the scheduled visit, and the subject should be fasting 
for approximately 8 hours prior to the visit. 


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normal. During this time, the subject may continue to use the standard emollient and the 
investigator-approved, medicated (non-steroid) shampoo as well as topical psoriatic 
therapy as recommended by the investigator which do not contain steroids. Systemic 
corticosteroids are also not permitted during this time. 
 
AEs that may be associated with the CST and that must be included in the informed 
consent/assent include: 
• Rare hypersensitivity reactions 
• Bradycardia 
• Tachycardia 
• Hypertension 
• Peripheral edema 
• Rash 
 
AEs associated with venipuncture and that must also be included in the informed 
consent/assent include: 
• Pain 
• Bruising 
• Bleeding at the puncture site 
• Fainting 
• Inflammation of the vein 
13.1.1 Post-Treatment Follow-Up (only if suppressed at the End of Study) 
These visits should continue approximately every four (4) weeks (no less than every 28 
days) until the subject’s HPA axis response has returned to normal or other satisfactory 
resolution is documented. These visits should occur such that the CST is performed at the 
same time (± one hour) as the CST performed at Visit 1 (Screening, Part B) and if possible, 
ideally the CST should be initiated between 7 and 9AM. The specific procedures performed 
at these visits are detailed in Section 10.6. 
13.2 
Pregnancy Tests 
UPTs will be performed at the study site if the site meets local country requirements to 
perform the testing (e.g., United States sites registered and conforms to Clinical Laboratory 
Improvement Amendments (CLIA) regulations for such testing [site possesses at a 
minimum a current valid CLIA Certificate of Waiver]) or at an appropriately registered 
reference laboratory. A UPT will be performed on all female subjects (Section 10.1) at 
Visit 1 (prior to CST), Visit 2 (prior to treatment) and at the end of study or if the subject 
withdraws prematurely. The investigator will report the UPT results on the CRFs, in the 
subject’s medical records and in any independent records maintained at the study site. The 
urine pregnancy test used must have a minimum sensitivity of 25mIU of β-hCG/mL of 
urine. 


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13.3 
Pharmacokinetic Tests 
Blood (approximately 5 mL) for PK analysis will be drawn three times: at Screening (pre-
application, time=0) and at Day 8 and Day 15 (unless IGA=0 at Day 8), approximately 
12 hours after the dose on the previous day. All eligible subjects will have blood drawn at 
Screening for baseline drug concentration in plasma. On Day 8, all subjects, regardless of 
lesion clearance, will have blood drawn for assessment of trough drug concentration in 
plasma. Prior to the visit, subjects will be reminded to record i) the 12-hour “clock” time 
that the test article was applied in the evening of the day before the visit (Day 7) and ii) 
withhold application of the morning dose of test article on the morning of the visit (Day 8) 
until after the trough PK blood draw has been taken. Following this trough PK blood draw, 
subjects will apply, under supervision from the study staff, the morning dose of test article 
to the designated area and the time of application will be recorded and the percent BSA 
treated with test article and percent BSA affected will be recorded. Subjects who have 
cleared their treated lesions by Day 8 will not apply the Day 8 morning dose (unless CST 
and EOS procedures need to be performed on Day 9). At the Day 15 visit, subjects who 
have continued to treat lesions will have a final PK blood sample collected approximately 
12 hours after their Day 14 evening application and just prior to the initiation of the CST.   
 
All blood samples will be processed, stored and transported per the methodology provided 
by the analytical laboratory. 
14. 
END OF STUDY CRITERIA 
At the end of each subject’s participation in the study, the investigator will complete an 
End of Study form for all completed and discontinued subjects.  
14.1 
Completion of the Study 
Subjects who complete the treatment as specified in the protocol and who complete the 
End of Study evaluations will be considered to have completed the study.   
14.2 
Subject Discontinuation 
A subject may be withdrawn from the study prior to completion for any of the following 
reasons: 
• Whenever the subject and/or parent/guardian decide it is in the subject’s best 
interest to withdraw. NOTE: if the subject and/or parent/guardian decide it is in the 
subject’s best interest to withdraw due to an AE then it should be classified as 
withdrawal due to an AE. 
• Whenever the investigator decides it is in the subject’s best interest to be withdrawn 
• AEs 
• Worsening of condition or treatment failure (in the opinion of the investigator) 
• Intercurrent illness which may, in the investigator’s opinion, significantly affect 
assessment of clinical status 


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• Noncompliance 
• Pregnancy 
• Lost to follow-up 
• Sponsor administrative reasons 
14.3 
Screen Failures 
If a subject is a screen failure due to Visit 1 laboratory results that show an abnormal pre-
CST serum cortisol level or abnormal HPA axis function (a low post-CST serum cortisol 
level), complete the Screen Failure CRF. No clinical evaluation or follow-up CST will be 
performed in these subjects; however, the laboratory results will be provided to the 
subject’s parent with a recommendation to follow up with the subject’s regular healthcare 
provider.  
 
If a subject withdraws prematurely during the treatment period for another reason, 
complete the CRF for the appropriate visit, then complete the End of Study CRFs including 
scheduling appropriately to obtain the End of Study CST assessment.   
 
Subject enrollment will continue until at least 20 subjects with both Screening and End of 
Study serum cortisol data (pre- and post-cosyntropin stimulation) have completed the study 
without any significant protocol violations (evaluable subjects). This may require the 
enrollment of approximately 25 subjects. 
14.4 
Study Termination 
The study may be terminated by the investigator or the Sponsor. If, in the opinion of the 
investigator, clinical observations made during the study suggest that it may be unwise to 
continue, he or she may stop the study. A study termination by the investigator will be 
reported to the Sponsor. 
 
In addition, a written statement fully documenting the reasons for this action will be 
submitted to the Sponsor by the investigator within five working days. 
 
In the event that the Sponsor chooses to discontinue or terminate the study, appropriate 
notification will be given to the investigator.  
15. 
ADVERSE EVENT REPORTING 
An adverse event (AE) is any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related.  
 
An AE (also referred to as an adverse experience) can be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a drug, without any judgment about causality. An AE can arise from any use of 


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the drug (e.g., off-label use, use in combination with any drug) and from any route of 
administration, formulation or dose, including an overdose. 
 
Information on the medical condition of subjects should begin following the subject’s 
written consent to participate in the study and a medical history should be taken at 
screening. During any wash out and baseline periods, any changes in the health of subjects 
should be recorded as changes in medical history unless an event occurred as a result of a 
study-related procedure and is unanticipated; where in such cases, the event should be 
recorded as an adverse event and reported to the Institutional Review Board (IRB) as an 
“unanticipated problem” in accordance with local procedures. Other changes in subject 
health information becomes AE data when the subject begins dosing with the test article 
and therefore AE data should be collected from the date of the first dose of test article. 
These data are considered treatment-emergent AEs.  
 
Timely and complete reporting of all AEs assists Therapeutics, Inc. (TI) in identifying any 
untoward medical occurrence, thereby allowing:  
1) protection of the safety of study subjects;  
2) a greater understanding of the overall safety profile of the test article;  
3) recognition of dose-related test article toxicity; 
4) appropriate modification of study protocols;  
5) improvements in study design or procedures; and  
6) adherence to worldwide regulatory requirements.  
 
Test article is defined as a pharmaceutical form of an active ingredient (or “primary 
operational component” for devices) or vehicle/placebo being tested or used as a reference 
in the study, whether blinded or unblinded. AEs may be either spontaneously reported or 
elicited during questioning and examination of a subject. All AEs must be completely 
recorded on the AE CRF. If known, the investigator should report the diagnosis of the 
underlying illness or disorder, rather than its individual symptoms. Subjects experiencing 
AEs that cause interruption or discontinuation of test article, or those experiencing AEs 
that are present at the end of their participation in the study should receive follow-up as 
appropriate. If possible, report the outcome of any AE that caused permanent 
discontinuation or that was present at the end of the study particularly if the AE is 
considered by the investigator to be treatment-related (i.e., definitely, probably, or possibly 
related to test article). 
15.1 
Adverse Event 
All AEs must be recorded on the AE CRF. AEs should be followed to resolution or 
stabilization (if possible), and reported as serious AEs (SAEs) if they become serious. 
 
The investigator will instruct the subject to report any adverse events that may occur during 
the study. At each visit, the investigator should ask the subject, in non-directive fashion, 
about any change in the subject’s overall condition since the previous visit. 


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The severity of each AE, as judged by the investigator, will be recorded on the appropriate 
AE CRF and will be graded according to the following scale: 
 
Mild - The adverse event is transient and easily tolerated by the subject. 
 
Moderate - The adverse event causes the subject discomfort and interrupts the 
subject's usual activities. 
 
Severe - The adverse event causes considerable interference with the subject’s 
usual activities, and may be incapacitating or life-threatening. 
 
The investigator must determine the relationship of the AE to the test article according to 
the following categories: 
 
Definite - An event that follows a reasonable temporal sequence from 
administration of the test article; that follows a known or expected response pattern 
to the test article; and that is confirmed by improvement on stopping or reducing 
the dosage, and reappearance of the event on repeated exposure (re-challenge). 
 
Probable - An event that follows a reasonable temporal sequence from 
administration of the test article; that follows a known or expected response pattern 
to the test article; and that is confirmed by improvement on stopping or reducing 
the dosage of the test article; and that is unlikely to have been caused by 
concurrent/underlying illness or other drugs, procedures, or other causes. 
 
Possible - An event that follows a reasonable temporal sequence from 
administration of the test article; that follows a known or expected response pattern 
to the test article; but may have been caused by concurrent/underlying illness, other 
drug, procedure, or other causes. 
 
Unlikely - An event that does not follow a reasonable temporal sequence from 
administration of the test article; that does not follow a known or expected response 
pattern to the test article, or most likely was caused by concurrent/underlying 
illness, other drug, procedure, or other causes, because of their known effects.  
 
Not Related - An event almost certainly caused by concurrent/underlying illness, 
other drug, procedure, or other causes. 
 
The investigator should categorize the outcome of the AE according to the following 
categories: 
 
 
Fatal - Termination of life as a result of an AE. 
 


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Not Recovered/Not Resolved - AE has not improved or the subject has not 
recuperated. 
 
 
Recovered/Resolved - AE has improved or the subject has recuperated. 
 
 
Recovered/Resolved with Sequelae - subject recuperated but retained the 
pathological conditions resulting from the prior disease or injury. 
 
 
Recovering/Resolving - AE is improving or the subject is recuperating. 
 
 
Unknown - Not known, not observed, not recorded or subject refused. 
 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions for which there is reason to conclude that the drug caused the 
event. For the purposes of prescription drug labeling, the term adverse reaction means an 
undesirable effect, reasonably associated with the use of a drug that may occur as part of 
its pharmacological action or may be unpredictable in its occurrence.  
 
A suspected adverse reaction is any adverse event for which there is a reasonable 
possibility that the drug caused the event.  
 
For the purposes of IND safety reporting, “reasonable possibility” means there is evidence 
to suggest a causal relationship between the drug and the adverse event. A suspected 
adverse reaction implies a lesser degree of certainty about causality than adverse reaction, 
which means any adverse event caused by a drug.  
 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed 
in the investigator brochure or is not listed at the specificity or severity that has been 
observed; or, if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan or elsewhere in the current 
application. For example, under this definition, hepatic necrosis would be unexpected (by 
virtue of greater severity) if the investigator brochure referred only to elevated hepatic 
enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral vasculitis would 
be unexpected (by virtue of greater specificity) if the investigator brochure listed only 
cerebral vascular accidents. "Unexpected," as used in this definition, also refers to adverse 
events or suspected adverse reactions that are mentioned in the investigator brochure as 
occurring with a class of drugs or as anticipated from the pharmacological properties of the 
drug, but are not specifically mentioned as occurring with the particular drug under 
investigation. 
 
Adverse skin reactions have been reported with the use of topical corticosteroids and may 
occur more frequently with high potency corticosteroids such as halobetasol cream and 
ointment. These reactions include stinging, burning, itching, erythema, acne, dry skin, 
folliculitis, leukoderma, telangiectasia, pustulation, hypertrichosis, acneiform eruptions, 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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hypopigmentation, perioral dermatitis, allergic contact dermatitis, vesicles, rash, 
paresthesia, urticaria, secondary infection, skin atrophy, striae and miliaria. (4, 5, 6). 
 
Systemic absorption of topical corticosteroids has produced reversible HPA axis 
suppression, manifestations of Cushing's syndrome, hyperglycemia and glucosuria in some 
patients. In rare instances, treatment (or withdrawal of treatment) of psoriasis with 
corticosteroids is thought to have provoked the pustular form of the disease (6). 
 
Risks associated with venipuncture and the CST are listed in Section 13.1. 
15.2 
Serious Adverse Event 
An event that is serious must be recorded on the AE CRF and on the Therapeutics, Inc. 
SAE Report Form, and requires expeditious handling to comply with regulatory 
requirements. SAEs will also be reported by TI to the Sponsor’s pharmacovigilance team. 
 
An adverse event or suspected adverse reaction is considered “serious” if, in the opinion 
of either the investigator or Sponsor, it results in any of the following outcomes: 
• Death. 
• Life-threatening event. 
• Inpatient hospitalization or prolongation of existing hospitalization. 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
• Congenital anomaly/birth defect. 
• Is an important medical event - defined as a medical event(s) that may not result in 
death, be life-threatening, or require hospitalization but, based upon appropriate 
medical judgment, may jeopardize the patient/subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in the definition above. 
Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse.  
 
Events NOT considered to be serious adverse events are: 
• Hospitalizations for the treatment, which was elective or pre-planned, of a pre-
existing condition that did not worsen, and 
• Treatment on an emergency, outpatient basis, for an event not fulfilling any of the 
definitions of “serious” given above and not resulting in hospital admission. 
 
Adverse events classified as “serious” by either the investigator or the Sponsor require 
expeditious handling and reporting to TI to comply with regulatory requirements. All 
serious AEs, whether related or unrelated to test article, must be immediately 
reported by telephone to the Medical Monitor and, in the event that he/she is 
unavailable, to the Project Manager listed on the first page of the protocol. Written 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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notification of all SAEs should be sent to the Project Manager by email or confirmed 
facsimile transmission. These include those SAEs listed in the protocol or investigator 
brochure and must include an assessment of whether there is a reasonable possibility that 
the drug caused the event.  
 
If only limited information is initially available, follow-up reports are required. Should the 
investigator become aware of a SAE (regardless of its relationship to test article) that 
occurs within 30 days after stopping the test article, the SAE must be reported in 
accordance with procedures specified in this protocol. In the event of death, if an autopsy 
is performed, a copy of the report should be sent to TI, if available. 
 
As required, TI will notify participating investigators of all suspected adverse reactions 
that are serious and unexpected. This notification will be in the form of an IND safety 
report of potential serious risks as soon as possible but no later than 15 calendar days after 
the Sponsor determines that the information is “reportable” according to the criteria listed 
in 21 CFR Section 312.32. These are: 
 
i) Serious and unexpected suspected adverse reactions, 
ii) Findings from other studies including epidemiological studies, pooled 
analyses or other clinical studies that suggest a significant risk in humans 
exposed to the test articles, 
iii) Findings from animal or in vitro tests that suggest a significant risk to 
humans exposed to the test articles, or reports of significant organ toxicity 
at or near the expected human exposure, and 
iv) Clinically important increases in the rate of occurrence of serious suspected 
adverse reactions. 
 
Upon receiving such notices, the investigator must review and retain the notice with the 
Investigator Brochure and immediately submit a copy of this information to the responsible 
IRB according to local regulations. The investigator and IRB will determine if the informed 
consent requires revision. The investigator should also comply with the IRB procedures 
for reporting any other safety information. Where required, submission of safety updates 
by the investigator to Health Authorities should be handled according to local regulations. 
15.3 
Pregnancy 
All female subjects must agree to use an effective form of birth control during the course 
of the study10 in a manner such that risk of failure is minimized. Prior to study enrollment, 
                                                 
10 Effective forms of birth control include hormonal contraceptives [oral, injectable, transdermal or 
intravaginal] or IUD for two cycles (e.g., eight weeks) prior to test article application, condom and 
spermicidal or diaphragm and spermicidal). Other acceptable forms of birth control include: a) abstinence 
for subjects who are not sexually active or b) if the subject is in a monogamous relationship with a partner 
who is sterile (e.g., vasectomy performed at least six months prior to the subject’s initiation of treatment). 
Subjects who become sexually active or begin to have relations with a partner who is not sterile during the 
trial must agree to use an effective form of birth control for the duration of the study. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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all female subjects must be advised of the importance of avoiding pregnancy during trial 
participation and the potential risk factors for an unintentional pregnancy.   
 
During the study, all female subjects should be instructed to contact the investigator 
immediately if they suspect they might be pregnant (e.g., missed or late menstrual period). 
 
All female subjects enrolling into the study must have a pregnancy test, prior to study 
therapy, if specified in the protocol. The study therapy must be withheld until the results 
of laboratory pregnancy testing are known. If pregnancy is confirmed during screening, the 
subject must not receive investigational product and must not be enrolled in the study.  
 
If a subject or investigator suspects that a subject may be pregnant at any time during the 
study the investigational product must be withheld until the results of laboratory pregnancy 
testing are available. If pregnancy is confirmed, the subject must not receive or apply 
further investigational product and must be discontinued from the study. 
 
If following initiation of study treatment, it is subsequently discovered that a trial subject 
was pregnant or may have been pregnant at the time of investigational product exposure, 
the investigator must immediately notify the Medical Monitor of this event, and record the 
pregnancy on the appropriate pregnancy surveillance form. The form will be sent to TI. 
The investigator must notify the IRB of any pregnancy associated with the study therapy 
and keep careful source documentation of the event. 
 
Protocol-required procedures for those subjects that are discontinued from the study must 
be performed on the subject unless contraindicated by pregnancy (e.g., x-ray studies). 
Other appropriate pregnancy follow-up procedures should be considered if indicated, 
including counseling of the subject by the investigator and her managing physician or 
health care provider (e.g., obstetrician). In addition, the investigator must report to TI, on 
the appropriate TI pregnancy surveillance form(s), any follow-up information regarding 
the course of the pregnancy, including perinatal and neonatal outcome. Although 
pregnancy itself is not an adverse event, any complications during pregnancy should be 
recorded as AEs (or SAEs – if they fulfill the SAE criteria). Abortion, whether accidental, 
therapeutic or spontaneous should be reported as a SAE. Offspring should be followed for 
a minimum of eight weeks. Any congenital anomaly/birth defect in a child born to a subject 
exposed to test article should be recorded as a SAE and details documented in the 
pregnancy surveillance form. 
16. 
BLINDING/UNBLINDING 
This is an open label study and all subjects will apply HBP Lotion, 0.05%.   


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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17. 
CLINICAL SUPPLIES 
17.1 
Test Article Information 
HBP Lotion, 0.05% will be purchased by the Sponsor or designee. Detailed information on 
the packaging/labeling, storage and preparation, dispensing and accountability are included 
in Appendix 3. 
17.2 
Supplies Provided by Therapeutics, Inc. 
• CRFs 
• Template source documents 
• Site Regulatory Binder 
• Standard bland emollient 
• Cosyntropin (Cortrosyn®) 
• UPT kits 
• Weighing scales (if necessary) 
• Timers 
17.3 
Supplies Provided by Investigator 
• Primary urine collection containers 
17.4 
Supplies Provided by the Clinical Laboratory 
• Supplies to collect and transport urine and blood samples to the clinical laboratory 
18. 
STATISTICAL CONSIDERATIONS 
18.1 
Sample Size 
Subject enrollment will continue until at least 20 subjects with both Screening and EOS 
serum cortisol data (pre- and post-cosyntropin stimulation) have completed the study 
without any significant protocol deviations (evaluable subjects). This may require the 
enrollment of approximately 25 subjects. 
 
No formal power calculations were performed to establish the sample size. The number of 
subjects enrolled who complete the study is historically consistent with other HPA studies. 
18.2 
Endpoints 
18.2.1 Efficacy Endpoints 
The primary objective of this study is to assess safety, not efficacy. However, IGA and 
percent BSA treated and affected with disease will be assessed to document any changes 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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that are observed with regard to IGA and percent BSA. Descriptive statistics will be 
provided for any changes from Baseline in IGA and percent BSA. 
18.2.2 Safety Endpoints 
HPA Axis Response to Cosyntropin 
HPA axis responses to stimulation by cosyntropin will be dichotomized to “normal” and 
“abnormal”. An abnormal HPA axis response is defined as a 30-minute post-stimulation 
serum cortisol level that is ≤18 µg/dL at the end of study.  
 
Plasma Levels of HBP 
Trough HBP concentrations in plasma on Day 8 and Day 15 will be calculated and 
summarized.  
 
Other Safety Endpoints 
Other safety endpoints will include AEs, LSRs associated with topical application of 
corticosteroids including telangiectasia, skin atrophy, burning/stinging, and folliculitis, 
UPTs, dosing compliance, and extent of exposure. 
18.3 
Statistical Methods 
All statistical analyses and summaries will be prepared using SAS® unless otherwise stated. 
All subjects enrolled in the study who were dispensed and applied test article at least once 
will be included in the analysis of safety and will be considered the Safety population. 
Subjects will apply the initial dose of test article in the clinic on Day 1. All enrolled subjects 
who applied at least one dose of test article and returned for at least one post-baseline visit 
will be included in the modified ITT (mITT) population. Subjects discontinued from the 
study at Visit 2 due to abnormal screening laboratory test results or other ineligibility 
criteria (screen failures) will be excluded from the HPA axis suppression summaries. 
Subjects included in the pharmacokinetic analysis (PK population) must not have any 
significant protocol deviations and must have at least an 80% - 120% dose compliance 
based on number of applications. Clinical study sites should make every effort so that 
subjects do not miss consecutive doses. 
 
Demographic and baseline characteristics (including the percent BSA affected and the 
percent BSA treated) will be summarized for the mITT, Safety and PK populations. In 
addition, demographic variables, AEs and primary reason for screen failure will be 
summarized separately for screen fail subjects. Frequency counts and percentages will be 
reported for categorical data and sample size, mean, SD, median, minimum and maximum 
will be reported for the continuous variables. 
 
Frequency counts and percentages for IGA scores at each visit and descriptive statistics 
(sample size, mean, SD, median, minimum and maximum) will be summarized for the 
percent BSA affected and the percent BSA treated with the test article at each visit. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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18.3.1 Safety Analyses 
Dosing Compliance 
Descriptive statistics will be used to summarize test article compliance for the mITT and 
PK populations. Measures of test article compliance will include the duration of treatment 
(number of days dosed), the total number of applications (determined from the actual 
number of applications reported by the subject), and the percent of expected doses applied. 
A subject will be considered compliant with the dosing regimen if the subject applies at least 
80% but no more than 120% of the expected number of applications. 
 
Extent of Exposure 
The total amount of test article used (grams of test article applied) will be calculated from 
the weights of the returned test articles. Descriptive statistics (mean, median, SD, minimum 
and maximum) will be determined for the total amount of test article used by each subject 
in the mITT and PK populations.  
 
An approximation of the amount of test article applied per cm2 prior to the collection of 
PK samples will be determined at Visit 3 from the estimate of the percent BSA treated with 
the test article. The BSA treated with test article (in square centimeters) will be determined 
from the Mosteller calculation (7). The amount of test article applied will be determined 
by weighing the bottle before and after the dose of test article is applied on the morning of 
Day 8. 
 
Urine Pregnancy Tests 
A listing of UPT results will also be prepared. 
 
Local Skin Reactions 
The frequency distributions of the severities of LSRs associated with topical application of 
corticosteroids including telangiectasia, skin atrophy, burning/stinging, and folliculitis will 
be summarized at Baseline and all follow-up visits. 
 
Adverse Events 
All subjects enrolled in the study who were dispensed and applied test article at least once 
will be included in the safety analysis (Safety population). All AEs reported during the 
study will be listed, documenting onset, whether therapy was required, any change in test 
article dosing, severity, possible relationship to test article, and outcome. Verbatim terms 
on the CRFs will be linked to PTs and SOC using the MedDRA mapping system. All 
reported AEs will be summarized by the number of subjects reporting AEs, SOC, PT, 
severity, and relationship to test article. 
18.3.2 HPA Axis Suppression Analyses 
The proportion of subjects manifesting adrenal suppression at the end of study (as defined 
in Section 18.2.2) will be summarized. The mean increases in serum cortisol levels after 
stimulation will also be summarized at the end of study. In addition, descriptive statistics 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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for the daily dose of test article will be tabulated separately for suppressed and non-
suppressed subjects. Post-treatment follow up data will be summarized for subjects 
determined to have laboratory based evidence of adrenal suppression at the end of study or 
early termination visit. 
18.3.3 Pharmacokinetic Analyses 
Trough HBP concentrations in plasma on Day 8 and Day 15 will be calculated and 
summarized.  
18.4 
Subgroup Analyses 
No subgroup analyses will be performed. 
18.5 
Interim Analyses 
No interim analyses will be performed. 
19. 
ETHICAL AND REGULATORY CONSIDERATIONS 
19.1 
Compliance with Good Clinical Research Practice 
This study will be conducted in compliance with the principles of the Declaration of 
Helsinki, with the current Good Clinical Practice guidelines and with other applicable 
regulations. The investigator and all study staff will conduct the study in compliance with 
this protocol. The protocol, informed consent/assent documents, recruitment 
advertisements and any amendments to these items will have IRB approval prior to study 
initiation. Voluntary informed consent will be given by every subject’s parent/guardian 
prior to the initiation of any study-related procedures. Subjects must provide written assent. 
The rights, safety and well-being of the study subjects are the most important 
considerations and prevail over the interests of science and society. All personnel involved 
in the conduct of this study must be qualified by education, training and experience to 
perform their assigned responsibilities. 
19.2 
Institutional Review Board and Informed Consent/Assent 
Before study initiation, the investigator must have written and dated approval from the IRB 
for the protocol, consent/assent form, subject recruitment materials/process (e.g., 
advertisements), and any other written information to be provided to subjects and their 
parent/guardian. The investigator should also provide the IRB with a copy of the product 
labeling, information to be provided to subjects and their parent/guardian and any updates. 
The investigator will submit documentation of the IRB approval to Therapeutics, Inc.  
 
The IRB-approved consent/assent form must include all elements required by FDA, state, 
and local regulations, and may include appropriate additional elements. 
 


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The investigator/designee will explain the study to each potential subject and the subject’s 
parent/guardian and the subject must indicate voluntary assent by signing and dating the 
approved informed assent form. The parent or legal guardian must provide informed 
consent for the subject. The investigator must provide the subject’s parent/guardian with a 
copy of the consent form and the subject with a copy of the assent form, in a language the 
subject understands.  
 
The investigator will maintain documentation that informed consent/assent was obtained 
prior to the initiation of any study-specific procedures. 
19.3 
Protocol Compliance 
The IRB-approved protocol must be followed except in the case of a change that is intended 
to eliminate an immediate risk to subjects. All protocol deviations must be documented. 
19.4 
Protocol Revisions 
Therapeutics, Inc. must prepare all protocol revisions. All protocol amendments must 
receive IRB approval prior to implementation. All administrative letters must be submitted 
to the IRB for their information. Copies of all correspondence with the IRB regarding this 
study must be sent to Therapeutics, Inc. 
 
New or altered consent/assent forms required by the IRB due to a protocol change must be 
signed by all subjects and the subject’s parent/guardian for those subjects currently enrolled 
in the study and must be used for any subsequent subject enrollment. 
19.5 
Study Monitoring 
Representatives of Therapeutics, Inc. and/or the Sponsor must be allowed to visit all study 
sites, to review study records and to directly compare them with source documents 
(including, but not limited to patient and hospital records), to discuss the study conduct 
with the investigator and study staff and to verify that the investigator, study staff and 
facilities remain acceptable for the conduct of the study. 
 
Representatives of government regulatory authorities may also evaluate the study records, 
source documents, investigator, study staff and facilities. 
 
The investigator should immediately notify Therapeutics, Inc. of any audits of this study 
by any regulatory agency, and must promptly provide copies of any audit reports. 
19.6 
Case Report Form Requirements 
The study will utilize validated 21CFR Part 11 compliant electronic data capture (EDC) 
software to collect CRF data. All requested information must be entered on the CRFs in 
the areas provided in a timely manner. When changes or corrections are made in the CRF, 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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the EDC system will maintain a complete audit trail of the person making the changes, the 
date and time of the change and the reason for the change. Only individuals listed on the 
Delegation of Responsibilities Log with responsibility for CRF completion may make 
entries on the CRFs. Usernames and passwords will be provided to each authorized user to 
allow access to the training module. Access to additional features and functions will not be 
enabled until the user has successfully completed the training. 
 
The investigator or physician sub-investigator must electronically sign and date each 
subject’s CRF. Individuals who will be providing electronic signatures must first submit 
documentation with a handwritten signature acknowledging that their electronic signature 
is a legally binding equivalent to their handwritten signature. 
19.7 
Reports to Institutional Review Board 
The investigator should provide the IRB with reports, updates, and other information (e.g., 
safety updates, protocol amendments, and administrative letters) according to regulatory 
requirements or Institution procedures. 
19.8 
Quality Assurance Audits 
Representatives from Therapeutics, Inc. and/or the Sponsor or a third party selected by the 
Sponsor may conduct a quality assurance audit of this study. During the audit, the 
investigator must provide the auditor with direct access to all relevant documents and 
discuss any findings with the auditor. 
 
In the event of an inspection by the FDA or other regulatory authorities, the investigator 
must give the inspector direct access to relevant documents and to discuss any findings 
with the inspector. The investigator must notify TI in the event of a FDA site audit. 
19.9 
Records Retention 
The investigator must maintain all study records (including test article disposition, 
informed consents, CRFs/data clarification forms, source documents, correspondence, 
regulatory documents, contracts, etc.) for a period of at least two years following the date 
of a marketing approval for the drug for the indication for which it is being investigated; 
or if no application is filed or if the application is not approved for such an indication, until 
two years after the investigation is discontinued and the FDA is notified.   
 
The investigator must contact Therapeutics, Inc. prior to destroying any records associated 
with this study. 
 
If the investigator withdraws from the study the records shall be transferred to a mutually 
agreed upon designee. Written notification of such a transfer must be given to Therapeutics, 
Inc. 
 


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Therapeutics, Inc. will notify the investigator/Institution in writing when the related records 
are no longer needed. 
19.10 Record Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in 
a manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the 
written permission of the subject or the subject’s guardian, except as necessary for 
monitoring by Therapeutics, Inc. or the Sponsor, the FDA or other regulatory authority, or 
the IRB. 
 
The investigator and all employees and coworkers involved with this study shall not 
disclose or use for any purpose other than performance of the study, any data, records, or 
other unpublished, confidential information disclosed to those individuals for the purpose 
of the study. Prior written agreement from Therapeutics, Inc. or the Sponsor must be 
obtained for the disclosure of any said confidential information to other parties. 


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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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20. 
REFERENCES 
1. 
Stoughton RB.  Vasoconstrictor assay--specific applications.  In:  Maibach HI, 
Surber C. eds. Topical Corticosteroids.  Basel: Karger; 1992: 42-53. 
 
2. 
Cortrosyn® (cosyntropin) for Injection (Package Insert).  Rancho Cucamonga, 
California: Amphastar Pharmaceuticals, Inc.: 2010. 
 
3. 
Evaluation of Endocrine Function in Clinical and Diagnosis Management by 
Laboratory Methods.  John Bernard Henry, 18th Edition, W.B. Saunders Company, 
1991. p. 331. 
 
4. 
Ultravate® Cream and Ointment (Package Insert).  Ranbaxy, Jacksonville, Florida; 
August 2012. 
 
5. 
000-0551-202 A Comparative Evaluation of the Adrenal Suppression Potential and 
Pharmacokinetic Properties of Twice Daily Halobetasol Propionate Lotion 0.05% 
versus Halobetasol Propionate Cream 0.05% in Subjects with Moderate to Severe 
Plaque Psoriasis Receiving Two Weeks of Treatment. Therapeutics, Inc., 2011. 
 
6. 
Investigator Brochure, Halobetasol Propionate Lotion, 0.05%; Edition 9.0. 
August 5, 2016. 
 
7. 
Mosteller RD.  Simplified calculation of body-surface area.  New Eng. J. Med. 
1987; 317, 1098. 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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APPENDIX 1 
SAMPLE SUBJECT INSTRUCTION SHEET 
A copy of the Subject Instruction Sheet will be provided to each study site. This sample 
instruction sheet may be used or modified by the investigator. If the instruction sheet is 
modified (other than the addition of “contact” information), the Subject Instruction Sheet 
will need to be reviewed by the Sponsor and approved by the governing IRB prior to use.  
 
The investigator should provide a copy of the instruction sheet to each subject at the 
Baseline Visit. 
 
NOTE:  Subjects should be scheduled to arrive at the office approximately one hour before 
the scheduled time for the blood draw for serum cortisol. This will help to ensure that the 
serum cortisol data will be evaluable.   
 
The Visit 1 CST should be initiated between 7 and 9AM. For each subject, any follow-
up CST (Visit 4 or at the end of study) should be initiated at approximately the same time 
as the Visit 1 CST was performed (± one hour). 
 
Visit 3 should be scheduled at the lower end of the visit window (e.g., Day 8 should be 
scheduled on Day 7 or 8). This will allow the scheduling of a “next” day visit (if necessary 
to perform the CST) within the visit window.  
 
To remain within the designated visit windows, it may be necessary to schedule Saturday 
clinic visits. 


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SAMPLE SUBJECT INSTRUCTION SHEET FOR PROTOCOL 177-0551-201 
 
Please follow these instructions carefully. Contact the study staff at the telephone number 
noted below if you have any questions about the study: 
 
Contact: 
 
 
 
 
 
 
At: 
 
 
 
 


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BACK OF INSTRUCTION SHEET 
 
STUDY VISIT SCHEDULE: 
VISIT 2: 
Date:                           Time:                              
VISIT 3: 
Date:                        Time:                           
VISIT 4:  
Date:                           Time:                                
NOTE:  Additional visits may be required at 4-week intervals (no less than every 28 days) 
if your laboratory test is abnormal after Visit 4. 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
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Sponsor Name: Sun Pharmaceutical Industries Ltd. 
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APPENDIX 2 
SAMPLE SUBJECT DIARY 
A copy of the Subject Diary will be provided to each study site. The investigator should 
provide a copy of the Subject Diary to each subject at the Baseline Visit (Visit 2/Day 1) 
and Visit 3 (Day 8) if all the affected areas of psoriasis are not completely clear. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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SAMPLE SUBJECT DIARY for PROTOCOL 177-0551-201 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
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APPENDIX 3 
TEST ARTICLE INFORMATION 
A 3.1 Test Article Packaging and Labeling 
HBP Lotion, 0.05% will be purchased by the Sponsor or designee. 
 
Test Article Labeling 
HBP Lotion, 0.05% will be labeled, at a minimum, with the following information: 
o Protocol No.: 177-0551-201 
o Site / Subject number: (to be filled in, XX/XXX) 
o Bottle unit number 
o Contents: Halobetasol Propionate Lotion, 0.05% 
o Storage statement 
A 3.2 Test Article Storage and Preparation 
The test article should be stored at the site between 15° C and 30° C (59° F and 86° F) in a 
secure area according to local regulations. 
A 3.3 Dispensing Test Article 
The study staff should assign the subject numbers in ascending order beginning with the 
lowest available subject number.   
 
The test article must be dispensed only to study subjects and only at study sites specified 
on the form FDA 1572 by authorized personnel as required by applicable regulations and 
guidelines. 
 
When dispensing the test article, record the site/subject number, bottle unit number(s), date 
dispensed and dispenser’s initials for each bottle of test article dispensed on the 
Investigational Test Article Accountability Log provided. Record the weight of each 
dispensed bottle to the nearest tenth gram (0.1 gram).   
 
On dispensing the test article for the first time (Visit 2/Day 1) provide each subject with 
two bottles (Bottle Units #1 and #2) and record the above information on the 
Investigational Test Article Accountability Log. The second bottle (Bottle Unit #2) of test 
article will be used in the event of loss, spillage or damage to the first bottle. A single bottle 
contains approximately 60 grams of test article and should last for one week and maintain 
compliance with the dosing regimen (maximum of approximately 50 grams per week). 
 
The subject will also be instructed to bring all the test articles provided to each clinic visit. 
 
At Visit 3 (Day 8) dispense a new bottle of test article (Bottle Unit #3). The subject should 
be instructed to use the second bottle and keep the third as the back-up.   
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 61 of 72 
TI SOP 305-A Protocol Template, Version 06 
When the subject returns each used bottle of test article, record the date of return and initials 
of the individual accepting the return for each bottle of test article on the same line of the 
Investigational Test Article Accountability Log as the dispensing information. Make every 
effort to obtain the return of all dispensed bottles of test article. Record the weights of all 
returned bottles on the Test Article Accountability Log. If these efforts fail, make a detailed 
note of the reason for the failure in the source documents and on the Comments page of 
the CRFs. 
A 3.4 Test Article Supply Records at Study Sites 
It is the responsibility of the investigator to ensure that a current record of test article 
disposition is maintained. Records or logs must comply with applicable regulations and 
guidelines, and should include: 
• Amount received placed in storage area. 
• Amount currently in storage area. 
• Label ID number or batch number. 
• Dates and initials of the person responsible for each product inventory 
entry/movement. 
• Amount dispensed to and returned by each subject, including unique subject 
identifiers. 
• Amount transferred to another area for dispensing or storage. 
• Non-study disposition (e.g., lost, wasted, broken). 
• Amount returned to Sponsor. 
• Amount destroyed at study site, if applicable. 
 
TI will provide forms to facilitate inventory control if the staff at the study site does not 
have an established system that meets these requirements. 
A 3.5 Dose Modifications 
The subject should not modify the treatment regimen without consultation with the 
investigator. In the event that the investigator believes dose modification is necessary 
(e.g., problems with tolerance) the subject’s care should be discussed with the Medical 
Monitor prior to making any dose modifications. All dose modifications must be reported 
on the appropriate Study Medication Compliance Form in the subject’s CRFs. 
A 3.6 Documentation of Application and Compliance 
A Study Medication Compliance Form will be used to report the frequency of test article 
applications for each subject. The date of the first application of test article will be recorded 
on the Study Medication Compliance Form. This form will also be used to record any 
changes from the twice daily application specified in the protocol (e.g., missed 
applications, investigator directed reduction in application frequency). The date and time 
of the last application of the test article will be recorded on the End of Study CRF. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 62 of 72 
TI SOP 305-A Protocol Template, Version 06 
 
A Subject Diary will be dispensed to subjects to record the application time of all doses 
and to record any missed doses of the test article (Appendix 2). Subjects will be instructed 
to bring the diary with them to each study visit. 
A 3.7 Return and Destruction of Test Article Supplies 
Upon completion or termination of the study all test article containers must be returned to 
the Sponsor or designee. All missing containers of test article must be explained on the 
completed Test Article Accountability Log. The study site must keep the original Label 
Pages and Test Article Accountability Log in the study file. A photocopy of the Test Article 
Accountability Log and Label Pages will be returned to TI.   
 
All shipments of returned test article must be clearly labeled with the investigator’s name, 
address, and the protocol number. 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 63 of 72 
TI SOP 305-A Protocol Template, Version 06 
APPENDIX 4 
COSYNTROPIN PACKAGE INSERT 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 64 of 72 
TI SOP 305-A Protocol Template, Version 06 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 65 of 72 
TI SOP 305-A Protocol Template, Version 06 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 66 of 72 
TI SOP 305-A Protocol Template, Version 06 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 67 of 72 
TI SOP 305-A Protocol Template, Version 06 
APPENDIX 5 
PROTOCOL AMENDMENTS 
PROTOCOL AMENDMENT # 1 
Date of Amendment: 04 November 2015 
 




Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 69 of 72 
TI SOP 305-A Protocol Template, Version 06 
Industries, Inc. (a Sun Pharma Company) Ferndale 
Laboratories, Inc. 
Protocol Approval 
The following individuals approve version 32.0 of the 177-
0551-201000 0551 209 
protocol 
dated 
August 
5, 
2016November 4, 2015. All changes to this version of the 
protocol must have prior written approval and require an 
amendment or administrative letter. 
 
 
 
Study Acknowledgement 
 
 
 
 
 
 
 
 
 
I have read this protocol and agree that it contains all the 
details necessary to conduct the study as described. I will 
conduct this study following this protocol and will make a 
reasonable effort to complete the study in the time noted. 
 
I will provide the contents of this protocol to study staff 
under my direct supervision that need to know the contents 
to conduct the study. I will discuss this information with the 
study staff to ensure they are fully informed about the study 
and the test articles. I will provide the contents of the 
protocol to the responsible Institutional Review Board(s). 
These disclosures may be made; providing the contents are 
not used in any other clinical study and they are not 
disclosed to any other person or entity without prior written 
consent from Sun PharmaFLI. This condition does not 
apply to disclosure required by government regulations or 
laws; however, I agree to give prompt notice to Sun 
PharmaFLI of any such disclosure. 
 
I understand the study may be terminated or enrollment 
suspended at any time by Sun PharmaFLI, with or without 
cause, or by me if it becomes necessary to protect the 
interests of the study subjects. 
 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 70 of 72 
TI SOP 305-A Protocol Template, Version 06 
Any additional information added to this protocol is also 
confidential and proprietary to Sun PharmaFLI and must 
be treated in the same manner as the contents of this 
protocol. 
… 
Protocol Number: 177-0551-201000 0551 209 
Version: 23.0 
Date of final version: August 5, 2016November 4, 2015 
Synopsis, 
Study 
Procedures 
Post-Treatment Follow-up Visits (Suppressed Subjects 
Only): Any subjects who have evidence of adrenal 
suppression at EOS will return approximately every four (4) 
weeks BUT no sooner than four (4) weeks (28 days) after 
the EOS visit, and subsequently approximately every four 
(4) weeks BUT no earlier than every four (4) weeks (>28 
days) thereafter for CST until the adrenal response returns 
to normal. Subjects with other ongoing AEs that require 
follow-up may also be followed per the discretion of the 
investigator. 
1. Background 
Halobetasol 
propionate 
(HBP) 
is 
a 
well-known 
corticosteroid with anti-inflammatory properties. It is 
indicated for the local topical treatment of various 
inflammatory skin disorders (e.g., psoriasis). 
 
 
 
 
 
 
 
 
 
6.1 Description 
 
 
10.6 
Post-Treatment 
Follow-Up 
Visits 
– 
Suppressed Subjects Only 
These visits are only required for subjects who have 
demonstrated abnormal CST consistent with suppression at 
the end of study and are returning for the follow-up CST as 
per Section 13.1.1. Subjects with other ongoing AEs that 
require follow-up may also be followed per the 
discretion of the investigator. 
Section 13.1 Cosyntropin 
Stimulation Test (CST) 
Perform the cosyntropin stimulation test as follows: 


Product Name: Halobetasol Propionate Lotion, 0.05% 
Protocol: 177-0551-201 
Sponsor Name: Sun Pharmaceutical Industries Ltd. 
Protocol Date: August 5, 2016, v3.0 
 
CONFIDENTIAL 
Page 71 of 72 
TI SOP 305-A Protocol Template, Version 06 
• Collect 
a 
pre-stimulation 
blood 
sample 
(approximately 6-7 mL) as specified in the 
Laboratory Manual. 
• Reconstitute one vial of cosyntropin (0.25 
milligrams) in sodium chloride for injection USP 
(the volume of sodium chloride in the package insert 
for Cortrosyn [Appendix 4] is 2 to 5 mL). 
• Inject the cosyntropin intravenously (the length of 
time during which the cosyntropin should be 
injected is 2 minutes [Appendix 4]). 
• Thirty minutes after completing the cosyntropin 
injection collect a post-stimulation blood sample 
(approximately 6-7 mL) as specified in the 
Laboratory Manual. 
13.3 
Pharmacokinetic 
Tests 
Blood (approximately 5 mL) for PK analysis will be 
drawn three times: at Screening (pre-application, 
time=0) and at Day 8 and Day 15 (unless IGA=0 at Day 
8), approximately 12 hours after the dose on the 
previous day. All eligible subjects will have blood drawn 
at Screening for baseline drug concentration in plasma.  
15.2 
Serious 
Adverse 
Event (SAE) 
An event that is serious must be recorded on the AE CRF 
and on the Therapeutics, Inc. SAE Report Form, and 
requires expeditious handling to comply with regulatory 
requirements. SAEs will also be reported by TI to the 
Sponsor’s pharmacovigilance team. 
17.1 
Test 
Article
Information 
 
 
 
Appendix 1 
SAMPLE SUBJECT INSTRUCTION SHEET FOR 
PROTOCOL 177-0551-201000 0551 209 
Appendix 2 
SAMPLE SUBJECT DIARY for PROTOCOL 177-0551-
201000 0551 209 
Appendix 3, A3.1 Test 
Article 
Packaging 
and
Labeling 
 
 
 
 
Test ArticleBottle Labeling 

SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
VERSION: 1.0 
 
DATE: 17Sep2019 
 
 
SPONSOR: 
Sun Pharmaceutical Industries, Inc. 
PROTOCOL NUMBER: 
177-0551-201 
TI PROJECT NUMBER: 
177-0551-201 
PROTOCOL TITLE: 
An Open Label Evaluation of the Adrenal 
Suppression Potential and Pharmacokinetic 
Properties of Twice Daily Halobetasol 
Propionate Lotion, 0.05% in Subjects 12 to 16 
Years 11 Months of Age with Plaque Psoriasis 
Receiving Two Weeks of Treatment 
ORIGINAL PROTOCOL DATE: 
October 21, 2015 
PROTOCOL AMENDMENT #1: 
November 4, 2015 
PROTOCOL AMENDMENT #2: 
August 5, 2016 
ADMINISTRATITVE AMENDMENT #1: 
October 28, 2016 
 


Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
 
 
 
 


Statistical Analysis Plan, v1.0 
 
Sponsor: Sun Pharmaceutical Industries, Inc. 
TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
 
 
 


Statistical Analysis Plan, v1.0 
 
Sponsor: Sun Pharmaceutical Industries, Inc. 
TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
ABBREVIATIONS 
AE 
Adverse Event 
BSA 
Body Surface Area 
CSR 
Clinical Study Report 
CST 
Cosyntropin Stimulation Test 
eCRF 
electronic Case Report Form 
EOS 
End of Study 
HBP 
Halobetasol Propionate 
HPA 
Hypothalamic-Pituitary-Adrenal 
IGA 
Investigator’s Global Assessment 
LSR 
Local Skin Reaction 
mITT 
modified Intent-to-Treat 
PK 
Pharmacokinetic 
PT 
Preferred Term 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
TI 
Therapeutics, Inc. 
UPT 
Urine Pregnancy Test 
 
 
 


Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
TABLE OF CONTENTS 
Statistical Analysis Plan .................................................................................................................. 1 
SAP Approval ................................................................................................................................. 2 
Abbreviations .................................................................................................................................. 4 
Table of Contents ............................................................................................................................ 5 
1. 
Introduction ............................................................................................................................. 7 
2. 
Purpose of the Analyses .......................................................................................................... 7 
3. 
Study Objectives and Endpoints ............................................................................................. 7 
3.1 
Objectives ....................................................................................................................... 7 
3.2 
Efficacy Endpoints .......................................................................................................... 7 
3.3 
Safety Endpoints ............................................................................................................. 7 
3.3.1 HPA Axis Response to Cosyntropin ........................................................................... 7 
3.3.2 Plasma Levels of Halobetasol Propionate ................................................................... 7 
3.3.3 Other Safety Endpoints ............................................................................................... 8 
4. 
Study Design ........................................................................................................................... 8 
4.1 
Schedule of Events .......................................................................................................... 9 
5. 
Definitions ............................................................................................................................. 11 
6. 
Clinical Evaluations .............................................................................................................. 11 
6.1 
Investigator’s Global Assessment ................................................................................. 11 
6.2 
Percent Body Surface Area Affected with Disease ...................................................... 12 
6.3 
Percent Body Surface Area Treated with Test Article ................................................. 12 
7. 
Safety Evaluations ................................................................................................................ 12 
7.1 
Cosyntropin Stimulation Test ....................................................................................... 12 
7.2 
Pharmacokinetic Tests .................................................................................................. 13 
7.3 
Adverse Events ............................................................................................................. 13 
7.4 
Local Skin Reactions .................................................................................................... 13 
7.5 
Urine Pregnancy Tests .................................................................................................. 14 
8. 
Statistical Methods ................................................................................................................ 14 
8.1 
General Considerations ................................................................................................. 14 
8.2 
Analysis Populations ..................................................................................................... 14 
8.2.1 Safety Population ...................................................................................................... 14 
8.2.2 Evaluable Population ................................................................................................. 14 
8.2.3 Pharmacokinetic Population ...................................................................................... 15 
8.3 
Final Analyses and Reporting ....................................................................................... 15 
8.4 
Sample Size ................................................................................................................... 15 
8.5 
Subject Disposition ....................................................................................................... 15 
8.6 
Screening and Baseline Assessments ........................................................................... 15 
8.6.1 Demographics ............................................................................................................ 15 
8.6.2 Medical History ......................................................................................................... 16 
8.6.3 Physical Examination ................................................................................................ 16 
8.6.4 Vital Signs, Height, and Weight ................................................................................ 16 
8.6.5 Baseline Clinical Evaluations .................................................................................... 16 
8.6.6 Baseline Local Skin Reactions .................................................................................. 16 


Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
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CONTROLLED & CONFIDENTIAL 
8.7 
Dosing Compliance ....................................................................................................... 16 
8.8 
Efficacy Evaluation ....................................................................................................... 16 
8.8.1 Analysis of Efficacy .................................................................................................. 16 
8.8.2 Statistical / Analytical Issues ..................................................................................... 17 
8.8.2.1 Handling of Dropouts or Missing Data .............................................................. 17 
8.8.2.2 Interim Analyses ................................................................................................ 17 
8.8.2.3 Multicenter Studies ............................................................................................ 17 
8.8.2.4 Multiple Comparisons / Multiplicity .................................................................. 17 
8.8.2.5 Examination of Subgroups ................................................................................. 17 
8.9 
Safety Evaluation .......................................................................................................... 17 
8.9.1 Extent of Exposure .................................................................................................... 17 
8.9.2 Adverse Events .......................................................................................................... 17 
8.9.3 HPA Axis Suppression Analyses .............................................................................. 18 
8.9.4 Pharmacokinetic Analyses ........................................................................................ 18 
8.9.5 Local Skin Reactions ................................................................................................. 18 
8.9.6 Urine Pregnancy Tests .............................................................................................. 18 
8.9.7 Concomitant Medications and Concurrent Therapies/Procedures ............................ 18 
9. 
Changes to Protocol .............................................................................................................. 19 
 
 


Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
1. INTRODUCTION 
This Statistical Analysis Plan (SAP) describes the planned statistical analyses to be performed for 
data from Protocol 177-0551-201, “An Open Label Evaluation of the Adrenal Suppression 
Potential and Pharmacokinetic Properties of Twice Daily Halobetasol Propionate Lotion, 0.05% 
in Subjects 12 to 16 Years 11 Months of Age with Plaque Psoriasis Receiving Two Weeks of 
Treatment”. 
 
This SAP was created using Clinical Protocol 177-0551-201 Version 3.0 dated August 5, 2016, 
Administrative Amendment #1 dated October 28, 2016, and the Case Report Forms (CRF) Version 
1.0 dated December 21, 2016. 
2. PURPOSE OF THE ANALYSES 
The purpose of this SAP is to outline the planned analyses to be completed to support the Clinical 
Study Report (CSR) for Protocol 171-0551-201. Any post-hoc or unplanned analyses not identified 
in this SAP will be clearly identified in the CSR. 
3. STUDY OBJECTIVES AND ENDPOINTS 
3.1 
Objectives 
The objective of this study is to determine the adrenal suppression potential and the 
pharmacokinetic (PK) properties of an investigational lotion formulation of halobetasol 
propionate, 0.05% (HBP Lotion) applied twice daily in subjects aged 12 to 16 years 11 months 
with stable plaque psoriasis. 
3.2 
Efficacy Endpoints 
The primary objective of this study is to assess safety, however, Investigator’s Global Assessment 
(IGA) and percent body surface area (BSA) treated and affected with disease will be assessed to 
document any changes that are observed with regard to IGA and percent BSA. 
3.3 
Safety Endpoints 
3.3.1 
HPA Axis Response to Cosyntropin 
Hypothalamic-pituitary-adrenal (HPA) axis responses to stimulation by cosyntropin will be 
dichotomized to “normal” and “abnormal”.
3.3.2 
Plasma Levels of Halobetasol Propionate 
Trough HBP concentrations in plasma on Day 8 and Day 15 will be calculated and summarized. 


Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
177-0551-201_sap_17Sep2019_v1.0.docx 
 
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CONTROLLED & CONFIDENTIAL 
3.3.3 
Other Safety Endpoints 
Other safety endpoints will include adverse events (AEs), local skin reactions (LSRs) associated 
with topical application of corticosteroids including telangiectasia, skin atrophy, burning/stinging, 
and folliculitis, urine pregnancy tests (UPTs), dosing compliance, and extent of exposure. 
4. STUDY DESIGN 
This is an open label, multicenter study of an investigational formulation of HBP Lotion, 0.05% 
in male and female subjects aged 12 to 16 years 11 months with stable plaque psoriasis. 
Approximately 25 subjects with stable plaque psoriasis on at least 10% of their BSA (excluding 
the face, scalp, groin, axillae and other intertriginous areas), who fulfill the inclusion/exclusion 
criteria will be enrolled at multiple study sites. All subjects will have a screening cosyntropin 
stimulation test (CST) to assess their HPA axis response at Visit 1 (Screening Visit). At Visit 2 
(Baseline), eligible subjects with normal adrenal function will be eligible to participate in the 
study. 
 
Subjects will apply HBP Lotion, 0.05% to all psoriasis plaques identified at Visit 2 twice daily 
(approximately every 12 hours) for the assigned treatment period or until the investigator verifies 
the subject’s psoriasis has cleared. All subjects will have a CST to reassess their HPA axis response 
at EOS (or earlier if the investigator verifies the subject’s psoriasis has cleared). 
 
 
 
Eligible subjects will have blood drawn at Screening for baseline drug concentration in plasma. 
On Day 8, all subjects, regardless of lesion clearance, will have blood drawn for assessment of 
trough drug concentration in plasma. At the Day 15 visit, subjects who have continued to treat 
lesions will have a final PK blood sample collected approximately 12 hours after their Day 14 
evening application and just prior to the initiation of the CST.






Statistical Analysis Plan, v1.0 
 
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TI Project: 177-0551-201 
 
Protocol Number: 177-0551-201 
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CONTROLLED & CONFIDENTIAL 
5. DEFINITIONS 
• The “Treatment Area” is defined as the entire body exclusive of the face, scalp, groin, 
axillae, or other intertriginous areas. 
• End of Study (EOS) visit is the visit at which psoriasis has cleared or end of the assigned 
treatment period. 
• A completed subject is a subject who completes the treatment as specified in the protocol 
and who completes the EOS evaluations. 
• A subject’s psoriasis is defined as cleared if, at any visit, the investigator reports a score of 
zero (0) for IGA. 
• Visit 1 is designated as Screening. 
• Visit 2 is designated as Baseline. 
• Visit 3 is designated as Day 8. 
• Visit 4 is designated as Day 15. 
6. CLINICAL EVALUATIONS 
6.1 
Investigator’s Global Assessment 
The IGA score (5-point scale of 0 to 4) is an evaluation of the overall severity of a subject’s 
psoriasis in the Treatment Area and takes into consideration the three individual characteristics of 
psoriasis (scaling, erythema, and plaque elevation). At Screening, Baseline Visit/Day 1, Day 8, 
and Day 15/EOS, the investigator will evaluate all active psoriasis plaques that are in the Treatment 
Area and report the single integer score that describes the overall severity of the subject’s psoriasis 
using the following scale: 


Statistical Analysis Plan, v1.0 
 
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Protocol Number: 177-0551-201 
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CONTROLLED & CONFIDENTIAL 
6.2 
Percent Body Surface Area Affected with Disease 
This is defined as the BSA which is affected with psoriasis within the Treatment Area. The percent 
BSA affected with psoriasis will be estimated at the Baseline Visit/Day 1, Day 8, and Day 15/EOS.  
6.3 
Percent Body Surface Area Treated with Test Article 
This is defined as the BSA which is affected with psoriasis within the Treatment Area that will be 
treated. In most cases there is no difference between percent BSA affected and percent BSA treated 
unless the affected BSA is too large to be treated with the drug dosing limitation of 50 grams per 
week (e.g., 3.5 grams per application). The percent BSA to be treated will be estimated at Baseline 
and Day 8. 
7. SAFETY EVALUATIONS 
7.1 
Cosyntropin Stimulation Test 
At Visit 1 (Screening Visit, Part B), a CST will be initiated for each subject between 7 and 9AM.   
 
At the EOS visit, a CST (and any follow-up CSTs) should be ideally initiated between 7 and 9AM 
but within ± one hour of the screening CST, after confirmation that the subject has not applied test 


Statistical Analysis Plan, v1.0 
 
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Protocol Number: 177-0551-201 
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CONTROLLED & CONFIDENTIAL 
article at least 8 hours prior to the visit. If these conditions are not met, the subject should be 
rescheduled for CST on the next day.  
 
If the results of the Visit 1 (Screening) CST indicate the subject has an abnormal HPA axis 
response (defined as a post-stimulation serum cortisol level of ≤ 18µg/dL), the subject should be 
classified as a screen failure and withdrawn from the study.  
 
If a subject’s EOS CST results show an abnormal HPA axis response (defined as a post-stimulation 
serum cortisol level of ≤ 18µg/dL), the test article will be considered to have caused adrenal 
suppression in the subject. The subject will be required to return for additional follow-up visits, no 
less than every four weeks, until the HPA axis response has been documented to return to normal. 
7.2 
Pharmacokinetic Tests 
Blood for PK analysis will be drawn three times: at Screening (pre-application, time=0), Day 8, 
and Day 15 (unless IGA=0 at Day 8), approximately 12 hours after the dose on the previous day. 
All eligible subjects will have blood drawn at Screening for baseline drug concentration in plasma. 
On Day 8, all subjects, regardless of lesion clearance, will have blood drawn for assessment of 
trough drug concentration in plasma. At the Day 15 visit, subjects who have continued to treat 
lesions will have a final PK blood sample collected approximately 12 hours after their Day 14 
evening application and just prior to the initiation of the CST.   
7.3 
Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. An AE can be any unfavorable and unintended sign (e.g., an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, 
without any judgment about causality. An AE can arise from any use of the drug (e.g., off-label 
use, use in combination with any drug) and from any route of administration, formulation or dose, 
including an overdose. 
 
The severity of an AE will be recorded as mild, moderate, or severe. The relationship between an 
AE and the test article will be classified as definitely related, probably related, possibly related, 
unlikely related, or not related. 
7.4 
Local Skin Reactions 
At all post-screening visits, the investigator or designee will observe or directly query the subject 
regarding LSRs known to be associated with topical application of corticosteroids. The severity of 
the following LSRs: telangiectasia, skin atrophy, burning/stinging and folliculitis will be recorded 
as 0-none, 1-mild, 2-moderate, or 3-severe. A LSR is to be recorded as an AE only if therapy or 
discontinuation of test article is required. 


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CONTROLLED & CONFIDENTIAL 
7.5 
Urine Pregnancy Tests 
A UPT will be performed on all female subjects at Visit 1 (prior to CST), Visit 2 (prior to 
treatment), and at EOS or if the subject withdraws prematurely.  
8. STATISTICAL METHODS 
8.1 
General Considerations 
This section presents the statistical approaches that are anticipated for the analysis of the study 
data. These approaches may at times require modifications due to unanticipated features of the 
data. Deviations from analyses summarized in this document will be noted in the CSR. 
 
All statistical analyses and summaries will be prepared using SAS® version 9.4 unless otherwise 
stated.  
 
Frequency counts and percentages will be reported for categorical data and sample size, mean, 
standard deviation (SD), median, minimum and maximum values will be reported for the 
continuous variables. 
 
In general, all summary tables will be supported by a relevant subject data listing which will be 
sorted by study site, subject identification, and visit, as applicable. Figures may be created to aid 
in the interpretation of results. 
8.2 
Analysis Populations 
8.2.1 
Safety Population 
All subjects enrolled in the study who were dispensed and applied test article at least once will be 
included in the analysis of safety and will be considered the Safety population. Subjects will apply 
the initial dose of test article in the clinic on Day 1. 
8.2.2 
Evaluable Population 
The Evaluable population will include those subjects in the Safety population who have both 
Screening and EOS serum cortisol data (pre- and post-cosyntropin stimulation) and meet the 
following criteria: 
 
• Meets all inclusion/exclusion criteria, including normal response to cosyntropin 
stimulation defined as a Screening CST with a 30-minute post-stimulation cortisol level 
>18 µg/dL. 
• Screening and EOS CST were conducted between 7-9 AM. 
• EOS CST was conducted within ± 1 hour of the Screening CST. 
• Applied at least 80% and no more than 120% of the expected number of applications and 
applied the final dose no more than 14 hours prior to the start of the CST test. 


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• Has not taken or applied any medications that may interfere with HPA axis function. 
• Do not have any other significant protocol deviations. 
 
HPA axis suppression analysis will be conducted on the Evaluable and Safety populations. 
 
8.2.3 
Pharmacokinetic Population 
Subjects included in the PK analysis (PK population) will include those subjects in the Safety 
population who do not have any significant protocol deviations and must have at least an 80% - 
120% dose compliance based on number of applications. 
8.3 
Final Analyses and Reporting 
Final database lock will occur after all subjects have completed the study assessment period (or 
withdrew from the study prematurely) and all subject data have been monitored and all queries 
resolved.  
 
Further exploratory analyses not necessarily identified in this SAP may be performed to support 
the clinical development program. Any post-hoc or unplanned analyses performed and not 
described in this SAP will be clearly identified as such in the CSR. 
8.4 
Sample Size 
No formal power calculations were performed to establish the sample size.  The number of subjects 
enrolled who complete the study is historically consistent with other HPA studies. 
8.5 
Subject Disposition 
The number and percent of subjects who were randomized in the study, in each analysis 
population, who completed the study, who withdrew from the study, and their reasons for 
withdrawal will be summarized. Subject disposition will be summarized using all subjects who 
signed informed consent/assent forms and were enrolled in the study. 
 
Subject data listings of the protocol deviations, if any, and analysis population identification will 
be provided. 
8.6 
Screening and Baseline Assessments 
8.6.1 
Demographics 
Demographic information including sex, age, race, and ethnicity will be summarized for the 
Safety, Evaluable, and PK populations, as well as, screen failures. 


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8.6.2 
Medical History 
Medical history will be provided in a subject data listing for the Safety population. 
8.6.3 
Physical Examination 
Physical examination abnormalities will not be provided separately, but will be included with 
medical history. 
8.6.4 
Vital Signs, Height, and Weight 
Descriptive statistics will be provided for height, weight, temperature, systolic and diastolic blood 
pressure, heart rate, and respiration rate for the Safety population. 
8.6.5 
Baseline Clinical Evaluations 
The Screening and Baseline severity scores for IGA will be tabulated for the Safety, Evaluable, 
and PK populations. The frequency distribution of the body areas affected by plaque psoriasis will 
be presented.  Descriptive statistics will be provided for the Percent BSA Affected and the Percent 
BSA to be Treated. 
8.6.6 
Baseline Local Skin Reactions 
The frequency distributions of the Baseline severities of LSRs associated with topical application 
of corticosteroids including telangiectasia, skin atrophy, burning/stinging, and folliculitis will be 
summarized for the Safety populations. 
8.7 
Dosing Compliance 
Descriptive statistics will be used to summarize test article compliance for the Evaluable and PK 
populations. Measures of test article compliance will include the duration of treatment (number of 
days dosed = last dose date - first dose date + 1), the total number of applications (determined from 
the actual number of applications reported by the subject), and the percent of expected doses 
applied. The expected number of doses for subjects who are clear at Day 8 and discontinue from 
the study is 14.  Subjects who continue to Day 15 or early term will have the compliance rate based 
on an expected 28 doses. A subject will be considered compliant with the dosing regimen if the 
subject applies at least 80% but no more than 120% of the expected number of applications. 
8.8 
Efficacy Evaluation 
8.8.1 
Analysis of Efficacy 
The primary objective of this study is to assess safety, not efficacy. However, IGA and percent 
BSA treated and affected with disease will be assessed to document any changes that are observed 
with regard to IGA and percent BSA. Frequency distributions of the observed and change from 
Baseline IGA severity scores will be presented for each visit for the Evaluable population. 


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Descriptive statistics will be provided for observed and changes from Baseline with respect to both 
the percent BSA affected and to be treated for the Evaluable and PK populations. 
8.8.2 
Statistical / Analytical Issues 
8.8.2.1 
Handling of Dropouts or Missing Data 
All summaries will be based on observed data only. Imputation of missing clinical data values will 
not be performed. For the PK analyses, concentrations reported as below the lower limit of 
quantitation will be imputed as zero.  
8.8.2.2 
Interim Analyses 
No interim analyses will be performed. 
8.8.2.3 
Multicenter Studies 
Data tabulations will be per study site, as well as, overall. 
8.8.2.4 
Multiple Comparisons / Multiplicity 
Not applicable. 
8.8.2.5 
Examination of Subgroups 
No subgroup analyses will be performed. 
8.9 
Safety Evaluation 
8.9.1 
Extent of Exposure 
The total amount of test article used (grams of test article applied) will be calculated from the 
weights of the returned test articles. Descriptive statistics (mean, median, SD, minimum and 
maximum) will be determined for the total amount of test article used by each subject in the Safety, 
Evaluable, and PK populations.  
8.9.2 
Adverse Events 
All AEs reported during the study will be listed, documenting onset, whether therapy was required, 
any change in test article dosing, severity, possible relationship to test article, and outcome. 
Verbatim terms on the CRFs will be linked to preferred terms (PTs) and system organ class (SOC) 
using the Medical Dictionary for Regulatory Activities (MedDRA) version 20.0. For all AE 
summaries, if a subject has more than one AE within a PT, the subject is counted once in that PT.  
If a subject has more than one AE within a SOC, the subject is similarly counted once in that SOC. 
 


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The number and percentage of unique subjects reporting any local and systemic treatment-
emergent AE will be summarized by SOC and PT. The number and percent of unique subjects 
reporting any local and systemic TEAE will also be summarized by SOC, PT, and maximum 
severity (mild, moderate, severe) and closest relationship to test article (not related, unlikely, 
possibly, probably, definitely related). AE summaries will utilize the Safety population. 
8.9.3 
HPA Axis Suppression Analyses 
Subjects discontinued from the study at Visit 2 due to abnormal screening laboratory test results 
or other ineligibility criteria (screen failures) will be excluded from the HPA axis suppression 
summaries.  
 
The proportion of subjects manifesting laboratory based evidence of adrenal suppression at EOS 
(as defined in Section 3.3.1) will be presented along with 95% confidence intervals for the 
Evaluable and Safety populations. The observed serum cortisol levels (pre-and post-cosyntropin 
stimulation) and the changes in serum cortisol levels after stimulation at Screening, EOS, and, if 
any, at follow-up visits will also be summarized. In addition, descriptive statistics for the daily 
dose of test article will be tabulated separately for suppressed and non-suppressed subjects.  
8.9.4 
Pharmacokinetic Analyses 
Morning trough concentrations of HBP in plasma at Screening, Day 8 and Day 15 will be 
summarized for the PK population using geometric mean, coefficient of variation in addition to n, 
mean, median, standard deviation, minimum and maximum. 
8.9.5 
Local Skin Reactions 
The frequency distributions of the observed and change from Baseline severities of LSRs 
associated with topical application of corticosteroids including telangiectasia, skin atrophy, 
burning/stinging, and folliculitis will be summarized for the Safety population at Baseline and all 
follow-up visits. 
8.9.6 
Urine Pregnancy Tests 
A listing of UPT results will also be provided for the Safety population. 
8.9.7 
Concomitant Medications and Concurrent Therapies/Procedures 
A subject listing of the concomitant medications will be provided. Concomitant medications will 
be coded using the World Health Organization (WHO) Drug Dictionary version September 2017 
and summarized by ATC Level 3 for the Safety population. A separate listing of concurrent 
procedures and therapies will also be provided. No coding of therapies or procedures will be 
performed. 


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9. CHANGES TO PROTOCOL 
The protocol defined the Safety, modified Intent-to-Treat (mITT), and PK populations. Since an 
efficacy analysis is not the primary endpoint for this protocol, the mITT population has been 
replaced with the Evaluable population to be used for the analysis of HPA suppression response. 
Requirements for inclusion in the Evaluable population are specified so that the CST are consistent 
between the subjects. 
 
The protocol included the determination of the approximate amount of test article applied per cm2 
prior to the collection of the PK samples at Visit 3 from the estimate of the percent BSA treated 
with the test article and the amount of test article applied based on the before and after weights of 
the dose prior to the blood draws. This data was not captured for this study, therefore, this 
determination will not be performed.