Clinical trial NCT02125279
Conditions: Psoriasis Vulgaris
Sponsor: Galderma R&D
Start date: 2014-05-01; Completion date: 2018-05-01
Enrollment: 54 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The objective of this study is to evaluate the safety and efficacy of up to 26 weeks of treatment with calcitriol 3 mcg/g ointment when used twice daily, without occlusion, to treat pediatric subjects (2 to 16 years and 11 months of age) with mild to moderate plaque psoriasis.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Calcitriol
Intervention descriptions: intervention 1: None

Protocol documents:
Prot_000.pdf: 
A Multicenter Open Label Uncontrolled Study of the Long Term Safety and Efficacy of Calcitriol 3 mcg/g
Ointment Applied Twice Daily for 26 Weeks in Pediatric Subjects (2 To 17 Years of Age) With Mild to
Moderate Plaque Psoriasis
                                                                          NCT Number: NCT02125279
Date: 07 Jan 2016


GALDERMA R&D
Protocol No.: RD.06.SPR.18131 V03 - 02 Dec 2015 eUS
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CLINICAL TRIAL PROTOCOL
PROTOCOL NUMBER: RD.06.SPR.18131
CONFIDENTIAL
This document contains confidential, proprietary information
All the information provided to the Investigator and his/her staff and all data obtained through 
this GALDERMA clinical trial protocol are confidential. The Sponsor reserves all proprietary 
rights. No information may be disclosed to any third party without prior written consent from 
GALDERMA.
 
Name
Reason for Signing
Date
Medical Advisor
07-Jan-2016
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TITLE PAGE
Title
A multicenter open label uncontrolled study of the long term safety and efficacy of calcitriol 3 mcg/g ointment 
applied twice daily for 26 weeks in pediatric subjects (2 to 16 years and 11 months of age) with mild to moderate 
plaque psoriasis
Project Name or CD number: 
Project Number:
Clinical Trial Phase:
Calcitriol 3 mcg/g ointment CD2027
746
Phase IV (Phase III*)
* for non US regions
IND Number: 62,151
EUDRACT Number: 2014-000710-53
Version Number: R03
SPONSOR:
Name:
GALDERMA R&D, LLC
Address:
14501 North Freeway
Ft. Worth, TX 76177
Telephone:
+1 817 961 5000
For any safety questions, please contact the Clinical Safety Officer (CSO) using the contact 
details provided in Section 7.2.3.2.2.
For any medical questions related to the clinical trial protocol, please contact the Medical Expert 
using the contact details below:
Name and Title:
Address:
Telephone:
E-mail:
This clinical trial will be performed in compliance with applicable regulatory requirements and 
Good Clinical Practice (GCP). This clinical trial protocol follows guidelines outlined by the 
International Conference on Harmonisation (ICH) and the GALDERMA template.
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TABLE OF CONTENTS
TITLE PAGE...............................................................................................................................................2
SYNOPSIS ...................................................................................................................................................8
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................................15
1
BACKGROUND AND RATIONALE...........................................................................................18
1.1
Medical background and short rationale for the clinical trial...............................................21
1.2
Drug profile ................................................................................................................................21
1.3
Risk/Benefit assessment.............................................................................................................21
2
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS .....................................23
2.1
Clinical trial objectives..............................................................................................................23
2.2
Clinical hypothesis .....................................................................................................................25
3
OVERALL CLINICAL TRIAL DESCRIPTION........................................................................25
4
CLINICAL TRIAL DURATION AND TERMINATION ..........................................................26
5
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION..........................26
5.1
Number of subjects ....................................................................................................................26
5.2
Clinical trial population characteristics...................................................................................26
5.3
Inclusion criteria ........................................................................................................................27
5.4
Exclusion criteria .......................................................................................................................28
5.5
Previous and concomitant therapies.........................................................................................31
5.5.1
Definition ...............................................................................................................................31
5.5.2
Categories ..............................................................................................................................31
5.5.3
Recording...............................................................................................................................31
5.5.4
Authorized concomitant therapies ......................................................................................32
5.5.5
Prohibited concomitant therapies........................................................................................32
5.6
Procedures/Reasons for subject discontinuation.....................................................................33
6
CLINICAL SUPPLIES...................................................................................................................35
6.1
Clinical supply identification and use ......................................................................................35
6.1.1
Study drug(s) description.....................................................................................................35
6.1.2
Subject Identification Number (SIN)..................................................................................35
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6.1.3
Method of treatment assignment.........................................................................................36
6.1.4
Kit number/randomization number....................................................................................36
6.1.5
Instructions for use and administration..............................................................................36
6.1.6
Other supplies........................................................................................................................37
6.2
Study drug(s) packaging and labeling......................................................................................38
6.3
Supplies management ................................................................................................................38
6.3.1
Accountability .......................................................................................................................38
6.3.2
Storage of clinical study drug(s) ..........................................................................................38
6.3.3
Dispensing and return ..........................................................................................................39
6.3.4
Treatment compliance management and record ...............................................................40
6.4
Dose modification.......................................................................................................................40
6.5
Blinding.......................................................................................................................................41
6.5.1
Verification of blinding.........................................................................................................41
6.5.2
Unblinding during the clinical trial.....................................................................................41
7
CLINICAL TRIAL ASSESSMENT..............................................................................................41
7.1
Efficacy assessments ..................................................................................................................41
7.1.1
Efficacy measurements.........................................................................................................41
7.1.1.1
IGA (as evaluated on all treated areas by a Board Certified (or any other 
regional equivalent) Dermatologist)...............................................................................41
7.1.1.2
Pruritus (as evaluated on all treated areas)...................................................................42
7.1.1.3
Other Assessments:..........................................................................................................42
7.1.2
Efficacy endpoints.................................................................................................................42
7.2
Safety assessment .......................................................................................................................42
7.2.1
Physical examination and vital signs...................................................................................43
7.2.1.1
Physical examination.......................................................................................................43
7.2.1.2
Vital signs .........................................................................................................................43
7.2.2
Laboratory safety tests .........................................................................................................44
7.2.2.1
IDMC Case Management................................................................................................46
7.2.3
Adverse Events......................................................................................................................46
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7.2.3.1
Definitions.........................................................................................................................47
7.2.3.1.1
Adverse events (AE)......................................................................................................47
7.2.3.1.2
Serious Adverse events (SAE).......................................................................................48
7.2.3.1.3
Adverse Events of Special Interest (AESIs) ..................................................................49
7.2.3.1.4
Unexpected adverse drug reaction...............................................................................49
7.2.3.1.5
Adverse event reporting period ....................................................................................50
7.2.3.1.6
Severity .........................................................................................................................50
7.2.3.1.7
Relationship to the study drug(s)..................................................................................50
7.2.3.2
Reporting procedures......................................................................................................51
7.2.3.2.1
Procedures for reporting Adverse Events.....................................................................51
7.2.3.2.2
Procedure for reporting a Serious Adverse Event........................................................52
7.2.3.2.3
Procedure for reporting an Adverse Event of Special Interest.....................................53
7.2.3.2.4
Procedures for reporting pregnancies..........................................................................55
7.3
Pharmacodynamic assessments ................................................................................................56
7.4
Pharmacokinetic assessment.....................................................................................................56
7.4.1
Blood sampling......................................................................................................................56
7.4.2
Plasma concentrations..........................................................................................................56
7.4.3
Pharmacokinetic measurements..........................................................................................57
7.5
Other assessments ......................................................................................................................57
7.6
Appropriateness of measurements ...........................................................................................57
8
CLINICAL TRIAL VISITS DESCRIPTIONS AND PROCEDURES......................................58
8.1
Description of clinical trial visits ..............................................................................................58
8.1.1
Screening visit........................................................................................................................58
8.1.2
Baseline visit ..........................................................................................................................59
8.1.3
Interim visits (Weeks 4 and 12) ...........................................................................................60
8.1.4
Week 26 Visit / Early Termination visit..............................................................................62
8.1.5
Week 30 Follow-up visit .......................................................................................................63
8.1.6
Unscheduled visits.................................................................................................................64
8.2
Subject instructions (other than study drug(s) administration)............................................64
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9
STATISTICAL METHODS PLANNED ......................................................................................65
9.1
Statistical and analytical plans..................................................................................................65
9.1.1
Analysis Endpoints................................................................................................................65
9.1.1.1
Efficacy Endpoints...........................................................................................................65
9.1.1.2
Key Safety Endpoints ......................................................................................................65
9.1.1.3
Pharmacokinetic Endpoint .............................................................................................65
9.1.2
Populations analyzed, evaluability and limitation / evaluation of bias ............................66
9.1.2.1
Safety Population.............................................................................................................66
9.1.3
Data presentation and graphics...........................................................................................66
9.1.4
Efficacy analysis methods.....................................................................................................66
9.1.4.1
Handling of missing data.................................................................................................66
9.1.4.2
Analyses of the efficacy endpoints..................................................................................66
9.1.5
Safety analysis methods........................................................................................................67
9.1.6
Pharmacokinetics analysis ...................................................................................................67
9.1.7
Subject disposition and baseline demographics.................................................................68
9.1.8
Subgroup analyses ................................................................................................................68
9.1.9
Interim analyses and data monitoring ................................................................................68
9.2
Sample size determination.........................................................................................................68
9.2.1
Assumptions...........................................................................................................................68
9.2.2
Sample size calculation.........................................................................................................68
10
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE ...........69
10.1
Personnel training......................................................................................................................69
10.2
Clinical monitoring ....................................................................................................................69
10.3
Data management ......................................................................................................................69
10.4
Quality assurance / audit / inspection.......................................................................................70
10.5
Changes in clinical trial conduct / amendments......................................................................70
10.5.1
Clinical trial conduct ............................................................................................................70
10.5.2
Amendments..........................................................................................................................70
11
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS ................71
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11.1
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) .......................71
11.2
Ethical conduct of the clinical trial...........................................................................................71
11.3
Subject information and consent..............................................................................................71
11.4
Contractual requirements.........................................................................................................71
11.5
Data collection and archiving....................................................................................................72
11.5.1
Data collection.......................................................................................................................72
11.5.2
Source documentation ..........................................................................................................72
11.5.3
Archives .................................................................................................................................72
11.6
Insurance ....................................................................................................................................73
11.7
Investigator and Administrative Structure .............................................................................73
12
LITERATURE REFERENCE LIST.............................................................................................74
13
APPENDICES .................................................................................................................................75
13.1
Appendix 1 Unauthorized Therapy..........................................................................................75
13.2
Appendix 2 Total Blood Sample Volumes and Number of Blood Sampling ........................77
13.3
Appendix 3 Calculation of Percent Body Surface Area Involved..........................................78
13.4
Appendix 4 Maximal daily dose and maximal application dose based on body 
weight. .........................................................................................................................................80
13.5
Appendix 5 NIH pediatric blood volume for research guideline...........................................82
LIST OF TABLES
Table 1
Clinical trial schematic ...........................................................................................................12
Table 2
Schedule of Assessments........................................................................................................13
Table 3
Description and usage of the study drug(s).............................................................................35
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SYNOPSIS
Clinical Trial Title:
A multicenter open label uncontrolled study of the long term safety and efficacy of calcitriol 3 mcg/g 
ointment applied twice daily for 26 weeks in pediatric subjects (2 to 16 years and 11 months of age) with 
mild to moderate plaque psoriasis
Short Title: Long term safety and efficacy study of calcitriol 3 mcg/g ointment in pediatric subjects with 
plaque psoriasis 
Clinical Trial phase:
Clinical Trial Population:
IV (III*)
* for non US regions
Plaque psoriasis in pediatric subjects
Clinical Trial objectives:
To evaluate the safety of up to 26 weeks of treatment with calcitriol 3 mcg/g ointment 
when used twice daily, without occlusion, to treat pediatric subjects (2 to 16 years 
and 11 months, Version R03) with plaque psoriasis.  
As a secondary objective, calcitriol plasma concentrations will be assessed at 
several time points throughout the study duration in a subset of children 2 to 6 years 
and 11 months old.
Clinical Trial design:
Multicenter, open-label uncontrolled study. 
Total number of subjects 
(Planned): 
As a screen failure rate of approximately 40 percent is expected, screening of 
approximately 167 subjects is planned in order to achieve the target of 100 subjects 
enrolled into the study.
PK investigations will be conducted in a subset of approximately 9 subjects aged 
between 2 to 6 years and 11 months old. 
Number of clinical trial 
centers (Planned):
Approximately 30 study centers
Region(s) / country(ies) 
involved (Planned):
United States, Canada, and Europe
Clinical trial duration:
The planned clinical trial duration (from FSI to LSO) is approximately 40 months.
The planned duration of recruitment (i.e. from FSI to LSI) is approximately 
34 months.
Duration of subject 
participation: 
Clinical trial participation for each subject is approximately 32 weeks.
Key Inclusion criteria
Male or female 2 to 16 years and 11 months of age (Version R03).
Specific for PK: Pediatric subjects 2 to 6 years and 11 months of age (inclusive at 
Screening) and with a minimum 3% BSA involvement.
Clinical diagnosis of stable mild to moderate plaque type psoriasis.
Subjects with an IGA score of 2 or 3 at Screening and Baseline.
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Key Exclusion criteria
Subjects with guttate psoriasis, pustular psoriasis, erythrodermic psoriasis or active 
infection (i.e., an infection associated with fever, swollen lymph nodes, and/or signs 
of localized inflammation of tissue and/or joints). Note: allergic or vasomotor rhinitis is 
not exclusionary.
Subject has hypercalcemia (serum albumin-adjusted calcium level above the upper 
normal range) at Screening.
Subjects with known or suspected disorders of calcium metabolism.
Subjects with liver dysfunction, defined as laboratory AST or ALT 2x ULN or total 
bilirubin 1.5x ULN.
Subjects with creatinine clearance 85 mL/min per 1.73 m2 at Screening.
The subject has urinary calcium:creatinine ratio above the upper normal range at 
Screening. 
The subject has a history or signs and symptoms of urolithiasis.
Subject has secondary hyperparathyroidism or PTH above upper limit of normal at 
Screening.  
Subjects with underlying systemic or other dermatological conditions that require the 
use of systemic supplements of calcium or vitamin D. (Subjects taking oral calcium 
and vitamin D for prophylactic purposes must be on a stable dose for at least 
4 weeks prior to screening and are not to exceed the Recommended Daily 
Allowance for calcium (1,300 mg for subjects aged 12-16 years and 11 months and 
1,000 mg for subjects less than 12 years) or Vitamin D (600 IU)1.
The Subject has Vitamin D deficiency (25(OH)D 20 ng/mL) at Screening (Note: 
Subjects with 25(OH)D 20 ng/mL at screening, may undergo re-screening after at 
least 4 weeks of Vitamin D deficiency treatment to determine eligibility).
Investigational product:
Name:
Vectical/Silkisointment
Internal code:
CD2027
Pharmaceutical form:
ointment
Strength/Concentration:
Calcitriol 3 mcg/g
Dosage (total daily dose):
Maximum of 0.5 g/kg of body weight or 28 grams daily (whichever is the lower)
Route:
Topical to psoriatic skin
Duration of administration:
26 weeks
Dose regimen:
Twice daily application (morning and evening)
Location of treated area:
Psoriatic skin (excluding face and scalp)
1 http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/, National Institutes of Health Office of Dietary 
Supplements, Strengthening Knowledge and Understanding of Dietary Supplements
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Comparator product:
Not Applicable
Name:
Internal code:
Pharmaceutical form:
[Strength/Concentration]:
Dosage (total daily dose):
Route:
Duration of administration:
Dose regimen:
Location of treated area:
Efficacy endpoints:
Percentage of subjects with an IGA Score of 0 (clear) or 1 (almost clear).
Change from Baseline in Pruritus.  
Change from Baseline in %BSA. 
Safety assessment:
Safety assessments include AE evaluation, vital signs/physical examination, and 
laboratory evaluations including hematology, chemistry, 1, 25(OH)2D, 25(OH)D, PD 
serum and urinary assessments (see Pharmacodynamic assessment below), 
eCRF AE forms will be reviewed periodically to monitor the ongoing safety of the 
study.
An Independent Data Monitoring Committee (IDMC) will be established for this study 
to monitor general subject safety and specifically parameters relating to calcium 
metabolism, and biochemistry.
Safety endpoints:
Safety endpoints include: Serum albumin-adjusted calcium, urine calcium:creatinine 
ratio, phosphorus, and PTH.
Pharmacokinetic 
assessment:
PK assessment: to evaluate the plasma concentration of calcitriol. One single blood 
sample at screening and baseline to assess the endogenous levels and its variability, 
then a single pre-dose blood sample (Ct) will be collected at Week 4, Week 12, Week 
26, and Week 30 in approximately 9 subjects 2 to 6 years and 11 months of age.
Pharmacodynamic 
assessment:
PD Serum (non-fasting): calcium, phosphorus, albumin (in order to calculate the 
serum albumin-adjusted calcium) and PTH.
PD Urine: Urine calcium and creatinine on 24-hour urine collection, whenever 
possible, or a urine sample after fasting for 4 hours in order to calculate Urine 
calcium : creatinine ratio.
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Principal statistical method: No inferential statistics are planned for this study.
The Safety Population is defined as comprising all of the subjects who have applied 
the study drug at least once.  All data will be summarized based on the Safety 
Population.
The laboratory parameters at scheduled visits and change from Screening at 
post-baseline visit(s) will be summarized descriptively by visit. A shift table for lab 
parameters at Screening versus the Week 26/Early Termination will be provided 
when appropriate.
The categorical variables will be summarized by frequency and percentage for each 
response category (N, %).  The continuous variables will be summarized using 
means, medians, minimum, maximum, and standard deviations for the data collected 
at each visit and the changes and percent changes from Baseline at each 
post-baseline visit when appropriate.
Treatment-emergent Adverse Events (TEAEs) will be tabulated in frequency tables 
by System Organ Class and Preferred Term based on the Medical Dictionary for 
Regulatory Activities (MedDRA).  Additional summary tables will be provided for AEs 
that are considered serious (SAEs), related to the study drug(s), severe, AESIs, and 
AEs leading to discontinuation.  For a given AE, a subject will be counted once even 
if he/she has experienced multiple episodes of that particular AE.  Subgroup 
summaries of AEs will be provided based on gender, age group, and race when 
appropriate. 
Ct will be submitted, after logarithmic transformation (Ln), to paired comparisons of 
Baseline and each subsequent time point. Ninety percent confidence intervals of the 
pairwise differences will be calculated using the Student’s t statistic. The limits of the 
intervals will be back-transformed into exponential to obtain 90% confidence intervals 
of the ratios of geometric means between time points, on the original scale.
PK/PD relationships will be investigated by correlating Ct with appropriate 
PD parameters, using Spearman coefficient and graphical illustrations.
Sample size:
Sample Size Justification:
Approximately 167 subjects will be screened to enroll approximately 100 subjects 
into the study. 
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Table 1
Clinical trial schematic
Screening (Approximately 167 subjects)

100 Subjects assigned to treatment with:
Group 1
n= 100
Treatment 
CD2027 calcitriol 3 mcg/g
Treatment Frequency
Twice daily
Treatment Duration
26 weeks
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Table 2
Schedule of Assessments
Clinical Trial Assessments
Screening 
Period
Treatment Period 
Follow up 
Period
Screening
(Day -14) 14
V1
Baseline16
(Week 0)
V2
Week 41
V3
Week 121
V4
Week 26 / 
ET1, 5
V5
Week 301
V6
Informed Consent / Assent Form /HIPAA/PIPEDA
X
Demographics
X
Medical History
X
Previous Therapies/Procedures8
X
Physical examination and Vital signs2
X
X
X
X
Inclusion/Exclusion Criteria
X
X3
Urine Pregnancy Test (post menarcheal)
X
X
X
X
X
X
Record % Body Surface Area involved
X
X
X
X
X
X
Routine Blood Chemistry and Hematology
X
X
X
X
X11
Urinalysis
X
X
X
X
X
Pharmacodynamic Serum9
X
X18
X
X
X
X11
PK Blood Sampling17
X
X
X
X
X
X
Pharmacodynamic Urine10
X
X13
X13
X11
25(OH)D & 1,25 (OH)2D
X
X
X
X11
IGA
X
X
X
X
X
X
Pruritus
X
X
X
X
X
X
Drug application
Twice a day from Baseline to Week 26 V515
Study drug Dispensing (D) and Accountability (A)4
D
D/A
D/A
A
Adverse Event information collection 7, 12
X
X
X
X
X
X
Concomitant Therapies/Procedures8
X
X
X
X
X
X
Moisturizer and cleanser dispensed6
X
X
X
X
Exit Form5
X
 
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1    Visit window of 3 days.
2    Physical Examination to include: weight and review of systems: skin, cardiovascular, respiratory, abdomen, head and neck, musculoskeletal, neurological, lymph nodes and 
psychological.   Height is to be evaluated at Screening visit only. Vital Signs to include: blood pressure, pulse rate
3   Reconfirm that subject continues to meet inclusion/exclusion criteria.
4    Total amount of Study Drug applied to involved skin should not to exceed 0.5 g/kg of body weight or 28g per day (whichever is the lower). First application to be made under the 
supervision of the investigator or designee. Record daily administration on dosing calendar. Dosing calendar to be checked at each visit after Baseline.
5   Or at any time in case of early termination.
6 The Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin Cleanser or equivalents will be provided by the Sponsor
7   Events occurring after the Informed Consent Form and Assent Form (when applicable) have been signed should be recorded as Adverse Events in the eCRF
8    Any therapy or medication other than study ointment will be noted on the Drugs/Therapies Form.  Subjects that require a wash-out period of a prohibited therapy for 2 weeks, 
should be screen failed and may re-screen 1 time after completion of the washout period.
9    PD Serum (non-fasting): calcium, phosphorus, albumin (in order to calculate the serum albumin-adjusted calcium) and PTH.
10 PD Urine: Urine calcium and creatinine on 24-hour urine collection, whenever possible, or a urine sample after fasting for 4 hours in order to calculate Urine calcium : creatinine 
ratio. Subjects that are toilet-trained should be actively encouraged to complete 24-hour urine collection. A urine collection container/material will be given to the subject / subject’s 
parent/legal guardian with the instruction to start collecting urine as of this visit and to bring the container back after the 24-hour/4-hour collection.
11 Laboratory testing (full panel) will be completed at Week 30 for subjects in the PK group. For all other subjects, laboratory testing at Week 30 will be completed at Investigator’s 
discretion.
12 Subjects with suspected kidney stones should temporarily discontinue study drug and will be referred to their Primary Care Physician (PCP) for care in tandem with Sponsor 
consultation of the IDMC.
13 The visit before: Distribute container and provide instructions for 24-hour urine collection to be started 1 day prior to Week 12 and Week 26/ET visits.  The study site should contact 
the parent/legal guardian 48 hours prior to the visit to remind them to start the urine collection.
14 Subjects may re-screen one time with written approval from the Sponsor prior to re-entry into the study.
15 At Baseline, the study nurse show the subject’s parents how to apply the drug.
16 Visit window of +/- 5 days.
17 For subjects in the PK group, a single blood sample at Screening and Baseline will be taken, then a single pre-dose blood sample will be taken at Weeks 4, 12, 26 and 30, to 
assess the calcitriol plasma concentration. The volume of each blood sample will be 5 mL. A total volume of 30 mL will be collected during the study for PK assessment.
18   Serum PD will be assessed during Baseline visit only for subjects 2 to 6 years and 11 months of age in whom PK analysis will be conducted in order to assess PK/PD relationships 
at Baseline for these subjects.
Unscheduled visit: When necessary and exceptionally, because of either an AE needing a specific treatment, AE leading to withdrawal from the study, laboratory result(s) that warrant 
further testing, or other reason.  
An ongoing dialogue between subject, parent/legal guardian and investigators focusing on all aspects of the trial is encouraged.   Any new information that arises in relation to the trial 
and that might affect the willingness of the subject and/or parent/legal guardian should be discussed.  This brief discussion should be documented during each study visit.
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Term
/
Per
%
Percent
C
Degrees Celsius
°F
Degrees Fahrenheit
1, 25(OH)2D
1, 25 dihydroxyvitamin D
25(OH)D
Vitamin D
AE 
Adverse Event
AESI
Adverse Event of Special Interest
ALP
Alkaline Phosphatase
ALT/ALAT (SGPT)
Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase)
approx 
Approximately (or use ‘about’, not C. or ca.)
AST/ASAT (SGOT)
Aspartate 
Aminotransferase 
(Serum 
Glutamic 
Oxaloacetic 
Transaminase)
AUC 
Area under Curve 
BID 
Twice Daily (Latin: bis in die)
BP
Blood Pressure
BSA
Body Surface Area
BUN
Blood Urea Nitrogen 
CDMS
Clinical Data Management System
CI
Confidence Interval
Cmax
Maximum Concentration
Cmin
Minimum Concentration
Ct
Pre-dose Plasma Concentration
CNS 
Central Nervous System 
C0
Trough Levels
CRA
Clinical Research Associate
CRO
Contract Research Organization
CSO
CSR
Clinical Safety Officer
Clinical Study Report
CV
Coefficient of Variation
DC
Discontinuation
DMP
Data Management Plan
eCRF
Electronic Case Report Forms
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Abbreviation
Term
e.g. 
For Example (Latin: exempli gratia)
Eq 
Equivalent (e.g., as in milli equivalent [mEq])
ET
Early Termination
etc
Et cetera
EU
European Union
Eur. Ph. or EP 
European Pharmacopoeia 
FDA
Food and Drug Administration
GCP 
Good Clinical Practice 
GGT
Gamma Glutamyl Transferase
GI
Gastro-intestine
Hb
Hemoglobin
Hct
Hematocrit
HIPAA
Health Insurance Portability and Accountability Act of 1996
ICF
Informed Consent Form
ICH
International Conference on Harmonisation 
i.e.
That is
IEC
Institutional Ethics Committee
IGA
Investigator’s Global Assessment of Disease Severity
IRB
Institutional Review Board
IRT
Interactive Response Technology
ITT
Intent-to-treat
IU
International Units
IUD
Intrauterine Device
IV 
Intravenous
LOCF
Last Observation Carried Forward
MedDRA
Medical Dictionary for Regulatory Activities
mL
Milliliter
N/A
Not Applicable
NDA
New Drug Application
NF
National Formulary
N or n
Number
p
Probability (as in significance level)
P
Page(s)
PD
Pharmacodynamics
PE
PIPEDA
Physical Examination
Personal Information Protection and Electronic Documents Act
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Abbreviation
Term
PK
Pharmacokinetics
PO 
Oral
PP
Per-Protocol
PT
Preferred term
PTH
Parathyroid hormone
PUVA
Psoralen-ultraviolet-light
PR
Pulse Rate
RBC
Red blood cell
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAS
Statistical Analyses System
SD
Standard Deviation
SEM
Standard Error of Mean
SIN
Subject Identification Number
SGOT (AST)
Serum glutamic oxaloacetic transaminase
SGPT (ALT)
Serum glutamic pyruvic transaminase
SOC
System Organ Class
SOP
Standard Operating Procedure
t½
Half-life
TEAE
Treatment Emergent Adverse Event
tmax
Time to Maximum Concentration
UA
Urinalysis
ULN
Upper Limit of Normal
UPT
Urine Pregnancy Test
US
United States
USP
United States Pharmacopeia
UV
Ultraviolet light
WBC
White Blood Cell
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1
BACKGROUND AND RATIONALE
Psoriasis vulgaris is one of the most common chronic skin diseases with a prevalence estimated 
at between 1.4% and 2.9% of the population. In approximately 35% of adults with psoriasis, 
the onset occurred in childhood (Farber 1999). In pediatric subjects and adolescents, plaque 
psoriasis is the most common form encountered, ranging from 34% to 84% in frequency and 
followed by guttate or “drop-like” psoriasis in 25% of cases (Lewkowicz 2004 and Nanda 1999).
Vitamin D derivatives are well-established, efficacious and safe topical drugs used in the therapy 
of chronic psoriasis. In the USA, only calcipotriol and calcitriol are on the market; they are 
indicated for the treatment of mild to moderate plaque psoriasis in adults.  The earliest approvals 
of calcitriol 3 mcg/g ointment occurred in 1995 in The Netherlands and Switzerland.  To date, 
calcitriol 3 mcg/g ointment is approved in 39 countries. It is marketed as Silkisointment in 
30 countries worldwide, including most European countries. Calcitriol 3 mcg/g ointment was 
approved in the USA on January 23, 2009 (Vectical, Galderma Laboratories).  
A total of 45 clinical studies have been conducted by the Sponsor to evaluate calcitriol ointment 
at various concentrations.  To date, 2974 subjects have been treated with calcitriol as part of the 
drug development program. Calcitriol 3 mcg/g ointment has been shown to be effective and safe, 
without affecting calcium homeostasis parameters in adult subjects.  Clinical studies have also 
shown that calcitriol is less irritating than calcipotriol.
Two pivotal Phase 3 studies (SPR.18053 and SPR.18054) with calcitriol 3 mcg/g ointment were 
completed in 2002. In both studies, the primary endpoint (Success Rate) was clinically and 
statistically superior for calcitriol 3mcg/g ointment compared to vehicle at Week 8. 
The superiority of treatment with calcitriol over vehicle was observed as early as Week 2, and 
sustained throughout the treatment period of 8 weeks. 
A PK/PD study (SPR.18102) was conducted from August 2006 to September 2009 on 
25 adolescents (12-17 years old; mean age: 14.7 years) with plaque psoriasis affecting 
10 to 35% BSA (mean: 17.8%). Serum calcitriol levels were investigated at baseline and after 
21 days of treatment with Vectical® (calcitriol 3µg/g ointment). Subjects received two 
applications per day and up to 15 g of formulation per application, depending on the total BSA 
and on the percentage of psoriasis-involved BSA. There was no significant variation of calcitriol 
levels during treatment. The overall mean (±SD) value of maximum calcitriol plasma levels 
(Cmax) was 76±24 pg/mL at Baseline (endogenous levels) and 73±22 pg/mL after 3 weeks of 
treatment. Regarding age stratification, the mean Cmax and AUC0-9hr or AUC0-12hr at Baseline 
were higher in the 12 to <15 years than in the 15 to 17 years (respectively 26% higher for Cmax 
and 19% higher for AUC0-9hr and AUC0-12hr).  The same tendency was observed after 21 days of 
application. The plasma calcitriol levels (Cmax) appeared to be 21% higher in the 
12 to <15 years age group compared to the 15 to 17 years age group and AUC0-9hr and AUC0-12hr, 
were approximately 17% higher. However, in each stratum, the calcitriol levels after 21 days of 
treatment were similar to the baseline levels. Overall, the repeated application of calcitriol 3 µg/g 
ointment did not resulted in an increased systemic exposure. 
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Furthermore, no correlation could be established between percentage of psoriasis-involved BSA 
and AUC0-9h in this study. Therefore, in study 18131, repeated applications of Vectical® are not 
expected to increase endogenous levels of calcitriol. 
The mean change for PD parameters were very minimal. No subjects had serum calcium or 
adjusted serum calcium values shifted from within the reference range at Baseline to above this 
range during the study. Serum PTH levels of one subject (Subject 9017) shifted from within the 
normal reference range (16 pg/mL) to below the normal reference range (6 pg/mL) at Day 15 but 
returned to within the reference range at Day 22 of study (19 pg/mL at Day 58).  
Although PTH levels remained within the normal reference range for the other subjects 
throughout the study, there was a trend for a decrease over time (mean change = -9.07 pg/mL for 
12 to <15 year group and -10.36 pg/mL for 15 to 17 year group). No statistically significant 
correlations between PK and PD parameters were noted. 
PTH will be monitored regularly throughout this study and all abnormal values and downward 
trends will be reviewed by the study Medical Expert and/or CSO as well as the IDMC. 
Additional studies have been conducted to evaluate the effect of calcitriol on calcium 
homeostasis.  One study of 59 subjects treated with calcitriol 3 mcg/g ointment for a total of 
20 weeks showed no significant change on calcium levels (Katz 1987).  An additional study of 
253 subjects treated with calcitriol 3 mcg/g ointment showed long-term efficacy after up to 
78 weeks of treatment and 2% (N=5) showed slightly elevated calcium levels.  Calcium levels 
normalized during the treatment period for four of the five subjects with hypercalcemia 
(Gerritsen 2001).
Galderma R&D has been conducting an extensive pediatric program as a Phase 4 requirement to 
extend the indication for calcitriol 3 mcg/g ointment to the pediatric population, which includes: 
SPR.18102 PK/PD study in adolescents aged 12-17 years (completed in 2009),
SPR.18104 PK/PD study in pediatric subjects aged 2-12 years (closed, 2015),
SPR.18132 Safety and Efficacy study in pediatric subjects aged 2-11 years (closed, 2015), 
and SPR.18131 Long-Term Safety (LTS) study in pediatric and adolescent subjects aged 
2-16 years and 11 months.  
In light of the recruitment challenges faced by the latter 3 studies conducted in parallel, the 
pediatric program was recently reconsidered by Galderma and reassessed by the US Food and 
Drug Administration (FDA).
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As a result of the discussion with the Agency in July 2015, the ongoing long-term safety study 
(SPR.18131) is being amended to include a PK assessment in a subset of 9 children aged 
2 to 6 years and 11 months old and the 2 ongoing studies (SPR.18104 and SPR.18132) will be 
closed to subject enrollment. These decisions were suggested and agreed by the Agency for 
logistical reasons and were not based on any safety concerns regarding the product’s use in 
children.
A summary and rationale of the present amendment follows:
Inclusion of PK assessments in this long-term safety study.  In discussion with FDA, it was 
agreed that a Pharmacokinetic assessment will be performed in approximately 9 subjects with 
plaque psoriasis aged 2 to 6 years and 11 months old with a minimum of 3% BSA 
involvement .
Addition of serum PD assessment at Baseline for subjects in the PK group so that PK/PD 
relationships can be investigated.
Number of enrolled subjects reduced from 140 to 100.
Study visits at Week 8 and Week 20 were removed. 
Management of parathyroid hormone (PTH) results falling below the lower limit of normal 
was revised.
The Independent Data Monitoring Committee (IDMC) will supervise the subjects’ safety as 
defined in the IDMC Charter. The IDMC will inform the Sponsor and suggest the action(s) to be 
taken, if safety signals are observed.
The specific roles of the IDMC include, but are not limited to:

Meet periodically to review individual data and summary analyses,

Assess data quality, including completeness,

Monitor biochemical and pharmacodynamic parameters,

Suggest additional data analyses,

Maintain and document any decisions and activities taken during IDMC meetings,

Recommend to the Sponsor whether recruitment/participation should be suspended for 
either individual participants or the entire study.
Further details regarding the IDMC’s role and activities will be outlined in a separate IDMC 
Charter document.
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1.1
Medical background and short rationale for the clinical trial
Safety and efficacy of calcitriol 3 mcg/g ointment in pediatric subjects under the age of 12 has 
not been previously studied.   The current study of the long-term safety of calcitriol 3 mcg/g 
ointment applied twice daily for up to 26 weeks is specifically designed to enroll and evaluate 
pediatric subjects 2 to 16 years and 11 months (Version R03) of age with mild to moderate 
plaque psoriasis. In addition, this study will allow the evaluation of plasma concentrations of 
calcitriol in a subset of 9 subjects aged 2 to 6 and 11 months. 
1.2
Drug profile
Calcitriol is the naturally occurring and biologically active metabolite of vitamin D3.  
Calcitriol inhibits the proliferation and stimulates differentiation of keratinocytes. It inhibits the 
proliferation of T-cells and normalizes the production of various inflammation factors. For these 
reasons, calcitriol is an effective drug in the topical treatment of psoriasis.  
At the time of writing this amended protocol, there have been no recent updates to the reference 
safety information for Vectical/Silkis, nor are any updates pending.
1.3
Risk/Benefit assessment
As mentioned in Section 1 above, calcitriol 3 mcg/g ointment has shown efficacy over vehicle in 
studies with adult subjects. 
The primary objective of this LTS study is to collect long-term (up to 26 weeks) safety data in 
children 2-16 years and 11 months of age (Version R03). As a secondary objective, calcitriol 
levels will be assessed at several time points throughout the study duration in a subset of children 
aged 2 to 6 years and 11 months old.
As mentioned in Section 1, childhood psoriasis is very prevalent, and an alternative to topical 
corticosteroid therapy in a pediatric population would be a desirable option. Calcitriol is a 
corticosteroid-sparing treatment that does not cause known steroid-related side effects such as 
skin atrophy and hypothalamo-pituitary axis (HPA) suppression.  
PK/PD data from adolescent subjects 12-17 years of age in study SPR.18102 are mentioned in 
Section 1 above, including abnormalities observed in PTH levels in a subset of subjects. 
PTH will be monitored regularly throughout this study and all abnormal values and downward 
trends will be reviewed by the study Medical Expert and/or CSO.  In addition, an IDMC will be 
in place for the duration of the study and will monitor laboratory and pharmacodynamic data as 
defined in the IDMC Charter.
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In controlled clinical trials in adults, hypercalcemia was observed in 24% (18/74) of subjects 
exposed to calcitriol 3 mcg/g ointment, and in 16% (13/79) of subjects exposed to vehicle. 
However, the increases in calcium and albumin-adjusted calcium levels were less than 
10% above the upper limit of normal. 
In the two pooled 8-week vehicle-controlled studies in 419 adult subjects, pruritus and 
discomfort pain were reported in 1% and 3% respectively for subjects treated with calcitriol 
3 mcg/g ointment, and 1% and 2% respectively for subjects exposed to vehicle. 
In a 52-week  open label study of 324 adult subjects, adverse events reported at a rate of greater 
than or equal to 3% of subjects treated with calcitriol 3 mcg/g ointment were lab test abnormality 
(8%), urine abnormality (4%), psoriasis (4%), hypercalciuria (3%), and pruritus (3%). 
Kidney stones were reported in 3 subjects and confirmed in two. 
All subjects enrolled in this LTS study will receive active treatment, calcitriol 3 mcg/g ointment. 
There is a risk of local irritation reactions, hypercalcemia, hypercalciuria and kidney stones 
associated with study participation. Multiple safety measures including regular monitoring of 
serum hematology, biochemistry and pharmacodynamic parameters pertaining to calcium 
homeostasis, as well as urine testing have been implemented to closely monitor subject safety. 
Further details regarding safety assessments are provided in Section 2.1. 
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2
CLINICAL TRIAL OBJECTIVES AND CLINICAL HYPOTHESIS
2.1
Clinical trial objectives
Safety Objectives:
The primary objective of this study is to evaluate the safety of up to 26 weeks of treatment with 
calcitriol 3 mcg/g ointment when used twice daily, without occlusion, to treat pediatric subjects 
(2 to 16 years and 11 months of age, Version R03) with mild to moderate plaque psoriasis. 
As a secondary objective, calcitriol plasma levels will be assessed at several time points 
throughout the study duration in a subset of children aged 2 to 6 years and 11 months old.
Safety Assessments:
Adverse Event recording at each study visit.
An Independent Data Monitoring Committee (IDMC) will be established for this study and 
will be responsible for securing the subjects’ safety including the review of the 
subjects’ laboratory results for: parathyroid hormone, calcium, phosphorus, albumin, and 
creatinine levels on an ongoing basis (as defined in the IDMC charter).  The IDMC will 
inform the Sponsor and recommend actions to be taken, if safety signals are observed.
Systemic Safety Parameters to be completed per the Schedule of Assessments (Table 2).

Vital signs (blood pressure and pulse rate)

Physical examination (weight, skin, cardiovascular, respiratory, abdomen, head and neck, 
gastrointestinal, 
respiratory, 
musculoskeletal, 
neurological, 
lymph 
nodes 
and 
psychological). Height is to be evaluated at the Screening visit only.

Routine safety laboratory parameters
Hematology: red blood cells, white blood cells with differential cell count,  hemoglobin, 
hematocrit, platelets 
Blood chemistry (non fasting) : total protein, ALT (SGPT), AST (SGOT), alkaline 
phosphatase, blood urea nitrogen, creatinine (calculated creatinine clearance), total and 
conjugated bilirubin 
Urinalysis: glucose, ketone, blood, protein, nitrite and leukocytes

Pharmacodynamic parameters
Serum(non fasting): calcium, phosphorus, albumin (in order to calculate the serum 
albumin-adjusted calcium), PTH 
Urine: Urine calcium and creatinine on 24-hour urine collection, whenever possible, or 
a urine sample after fasting for 4 hours in order to calculate Urine calcium : creatinine 
ratio.  Subjects that are toilet-trained should be actively encouraged to complete the
24-hour urine collection.
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
Other Assessments
1, 25(OH)2D. 
25(OH)D.
Urine Pregnancy Test for post menarcheal females (including subjects who become 
post-menarcheal during study participation). 
Efficacy Objectives:
To evaluate the long-term efficacy of up to 26 weeks of treatment with calcitriol 3 mcg/g 
ointment when used twice daily, without occlusion, to treat pediatric subjects (2 to 16 years and 
11 months of age, Version R03) with mild to moderate plaque psoriasis.
Efficacy Assessments:
Investigator’s Global Assessment of Disease Severity (Will be referred to as the IGA score in 
this document) [IGA scale is described in Section 7.1.1.1].
Pruritus. 
Pharmacokinetic (PK) Assessment:
Plasma concentration of calcitriol (1, 25(OH)2D) will be assessed using a single pre-dose 
blood sample (Ct) in a subset of approximately 9 subjects aged between 2 to 6 years and 
11 months old. 
Other Assessments:
Percent Body Surface Area (BSA) involved. 

The % BSA involved will be assessed using the methodology shown in 
Section 13.3, Appendix 3.
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2.2
Clinical hypothesis
Long term use (26 weeks) of calcitriol 3 mcg/g ointment is safe and efficacious in pediatric 
subjects (2 to 16 years and 11 months of age, Version R03) with mild to moderate plaque 
psoriasis.
The calcitriol absorption in pediatric subjects (2 to 6 years and 11 months of age) is expected to 
be comparable to that in adults and adolescents, with no significant impact on calcium/ 
phosphorus metabolism.
3
OVERALL CLINICAL TRIAL DESCRIPTION
This is an open-label, uncontrolled, multicenter long-term safety and efficacy study in pediatric 
subjects (age 2-16 years and 11 months, Version R03) with mild to moderate plaque psoriasis.  
Approximately one hundred (100) subjects will be enrolled into this study. A subset of enrolled 
subjects (approximately 9 among the 100) will meet the PK requirements: pediatric subjects aged 
2 to 6 years and 11 months (inclusive at Screening) and with a minimum 3% BSA involvement.
Qualified subjects will receive calcitriol 3 mcg/g ointment for a period of up to 26 weeks. 
The subject’s parent/legal guardian or the subject under the responsibility of the parent/legal 
guardian will apply a thin film of study drug as needed to cover all involved areas twice daily, 
without exceeding a maximum of 0.5 g/kg of body weight or 28 g daily (whichever is the lower).  
If the subject experiences complete clearing of psoriasis per physician assessment 
(i.e. an IGA of 0), the subject should discontinue the study drug but continue to follow the visit 
schedule through the Week 26 visit.  Treatment with study drug should be resumed if the 
IGA score is 0 and 4. 
Subjects will be evaluated at screening, baseline and Weeks 4, 12, 26, and 30 as described in the 
Schedule of Assessments (Table 2). A visit window of ± 5 days will be allowed for Baseline and 
a visit window of ±3 days will be allowed at the visits from Weeks 4 through 30. 
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4
CLINICAL TRIAL DURATION AND TERMINATION
The planned clinical trial duration (from FSI to LSO) is approximately 40 months. The date of 
end of the clinical trial is defined as the date of the last visit of the last subject who participates in 
the clinical trial.
The planned duration of recruitment (i.e. from FSI to LSI) is approximately 34 months.
Clinical trial participation for each subject is approximately 32 weeks.
GALDERMA may decide to prematurely terminate or suspend the participation of a particular 
clinical trial center (for example, for non-inclusion or non-compliance with clinical trial protocol, 
regulation, or GCP) or prematurely suspend the clinical trial (for example, for safety, study 
drug(s) quality, regulatory, efficacy, or logistical reasons) at any time with appropriate 
notification.
5
SELECTION AND DISPOSITION OF CLINICAL TRIAL POPULATION
5.1
Number of subjects
As a screen failure rate of approximately 40 percent is expected, approximately 167 subjects may 
have to be screened in order to get 100 subjects enrolled. A subset of approximately 9 subjects 
will be enrolled to meet the PK requirements (see Section 5.2).
5.2
Clinical trial population characteristics
In order to be eligible for the clinical trial, subjects must fulfill all of the following inclusion 
criteria and none of the exclusion criteria. 
Approximately 100 male or female subjects, 2 to 16 years and 11 months of age (Version R03), 
diagnosed with mild to moderate plaque psoriasis are to be enrolled in this multicentre open label 
uncontrolled study of the long term safety and efficacy of calcitriol 3 mcg/g ointment applied 
twice daily for 26 weeks. A subset of approximately 9 subjects will be enrolled to meet the 
PK requirements: pediatric subjects 2 to 6 years and 11 months of age (inclusive at Screening) 
and with a minimum 3% BSA involvement.
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5.3
Inclusion criteria
1.
Male or female 2 to 16 years and 11 months of age (Version R03).
2.
Specific for PK: Pediatric subjects 2 to 6 years and 11 months of age (inclusive at 
Screening) and with a minimum 3% BSA involvement.
3.
Clinical diagnosis of stable mild to moderate plaque type psoriasis. 
4.
Subjects with an IGA score of 2 or 3 at Screening and Baseline.
5.
Female of non-childbearing potential (pre-menarcheal).
6.
Female of childbearing potential with a negative urine pregnancy test (UPT) at visit(s) 
Screening (Day -14) and Baseline (Day 0). 
7.
Female of childbearing potential who:
7.1.
has been strictly abstinent 1 month prior to baseline and agrees to continue for the 
duration of the clinical trial,
7.2.
And/or agrees to use a highly effective and approved contraceptive method(s) during 
the study and for at least 1 month after the last study drug application.  A highly 
effective method of contraception is defined as:
7.2.a.
combined oral contraceptives (estrogens and progesterone) or implanted or 
injectable contraceptives with a stable dose for at least 1 month prior to baseline 
8.
Willing and able to comply with all of the time commitments and procedural requirements 
of the clinical trial protocol.
9.
Parent or legal guardian must understand and sign an Informed Consent Form (ICF) at 
screening, prior to any investigational procedures being performed. 
10.
If capable to give assent to decisions about participation in research, subject may sign an 
Assent Form to participate. In addition the subject must also have a parent or guardian sign 
the Informed Consent Form and HIPAA (USA only) or PIPEDA (Canada only) and is 
willing to share personal information and data as verified by signing a written authorization 
at Screening visit prior to any study related procedures being performed.
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Rationale:
1 to 4: In order to select a suitable pediatric population for the clinical trial. Overall age range 
is based on recent agreements with FDA and must be followed once the protocol amendment is 
implemented.
5 to 7: Since the safety of the Investigational Product for pregnant women has not been 
established yet.
8. To ensure protocol compliance and consistency of study data.
9 to 10: To ensure that all subjects are fully informed of the study requirements and only subjects 
providing written consent are included in the clinical trial.
5.4
Exclusion criteria
1.
Subjects with guttate psoriasis, pustular psoriasis, erythrodermic psoriasis or active 
infection (i.e., an infection associated with fever, swollen lymph nodes, and/or signs of 
localized inflammation of tissue and/or joints). Note: allergic or vasomotor rhinitis is not 
exclusionary.
2.
Any newly diagnosed genetic or congenital condition, uncontrolled or serious disease, or 
any medical or surgical condition, that may either interfere with the interpretation of the 
clinical trial results, and/or put the subject at significant risk (according to Investigator’s 
judgment) if he/she participates in the clinical trial.
3.
Known or suspected allergies or sensitivities to any components of any of the study drugs 
(see Investigator’s Brochure/Product label).
4.
Female who is lactating.
5.
Female who intends to conceive a child during the clinical trial.
6.
Current participation in any other clinical trial of a drug or device OR participated in a 
clinical trial of a drug or device within 1 month prior to baseline.
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7.
The subject has received, applied or taken the following treatments within the specified 
time frame prior to the Baseline visit:
Topical treatment(s) or Procedures:
Corticosteroids or topical immunomodulators
2 weeks
Tar (on areas to be treated with study drug)
2 weeks
Vitamin D derivatives
2 weeks
Vitamin A derivatives
2 weeks
Intralesional steroid injections
4 weeks
Systemic treatment(s):
Homeopathic or herbal preparations 
1 weeks
Calcium containing products
2 weeks
Immunomodulators and biologics known to affect psoriasis
4 weeks
Corticosteroids or ACTH analogs
4 weeks
Phototherapy/PUVA therapy
4 weeks
Laser therapy
4 weeks
8.
The subject or subject’s parent /legal guardian is unwilling to refrain from use of prohibited 
medication during the clinical trial (see Section 5.5.5).
9.
The subject is vulnerable (such as deprived from freedom) as defined in Section 1.61 of 
International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice 
(GCP).
10.
The subject has hypercalcemia (serum albumin-adjusted calcium above the upper normal 
range) at Screening.
11.
The subject has urinary calcium:creatinine ratio above the upper normal range at 
Screening.
12.
The subject has history or signs and symptoms of urolithiasis.  
13.
Subjects with known or suspected disorders of calcium metabolism.
14.
Subjects with liver dysfunction, defined as laboratory AST or ALT 2x ULN or Total 
bilirubin 1.5x ULN.
15.
Subjects with creatinine clearance 85mL/min per 1.73 m2 at Screening. (Shull, et al, 1978) 
Note: 
Creatinine clearance is to be calculated using the Schwartz Equation:
Creatinine Clearance = k x H/Scr.  
For children 1-12 and adolescent girls 13-16 years and 11 months old, k=0.55.  For adolescent 
boys 13-16 years and 11 months old, k=0.7. H=height at screening (cm).  Scr=serum creatinine 
(mg/dL) at screening. (Schwartz 1976).
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16.
Subjects with concomitant medical or dermatological disorder(s), which might preclude 
accurate evaluation of the psoriasis.
17.
Subjects with underlying systemic or other dermatological conditions that require the use 
of systemic supplements of calcium or vitamin D. (Subjects taking oral calcium and 
vitamin D for prophylactic purposes must be on a stable dose for at least 4 weeks prior to 
screening and are not to exceed the Recommended Daily Allowance for calcium (1,300 mg 
for subjects aged 12-16 years and 11 months and 1,000 mg for subjects less than 12 years) 
or Vitamin D (600 IU).
18.
The Subject has Vitamin D deficiency (25(OH)D 20 ng/mL) at Screening 
(Note: Subjects with 25(OH)D 20 ng/mL at screening, may undergo re-screening after at 
least 4 weeks of Vitamin D deficiency treatment to determine eligibility.).
19.
The subject is planning excessive exposure to the sun or ultraviolet light during the study 
(i.e. natural or artificial sunlight, including tanning booths and sun lamp).
20.
Subjects with clinically significant blood loss within the last 3 months prior to screening, 
per Investigator discretion.
21.
The Subject has clinically significant abnormal values of the safety laboratory parameters 
at Screening (See Section 7.2.2).
22.
The Subject has secondary hyperparathyroidism or PTH above Upper Limit of Normal at 
Screening.
Rationale:
1: These conditions are not part of the proposed label indications, plaque psoriasis.
2 to 3; 10 to22: These subjects are at risk and in order to enable appropriate evaluation.
4, 5 The safety of the Investigational Product for pregnant or nursing women has not been 
established yet.
6: To secure integrity of the study.
7 to 8: In order to exclude the influence of concomitant therapies on the evaluation of this study.
9: Protection of subject rights.
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5.5
Previous and concomitant therapies
5.5.1
Definition
Previous therapies are defined as therapies that have been stopped within the last 6 months prior 
to the screening visit for non-psoriasis-related therapies; for psoriasis-related therapies, 
all medications and procedures must be reported as previous therapy in the e CRF. 
Concomitant therapies are defined as follows:

any existing therapies ongoing at the time of the screening visit,

any changes to existing therapies (such as changes in dose or formulation) during the 
course of the clinical trial, or

any new therapies received by the subject since the screening visit.  
5.5.2
Categories
The following two categories are to be considered for previous and concomitant therapies: 

Drugs/therapies including but not limited to, prescription, over-the-counter (OTC), birth
control pills/patches/hormonal devices, vitamins, moisturizers, sunscreens, herbal 
medicines/supplements, and homeopathic preparations.

Medical and surgical procedures including, but not limited to, laser/radiation procedures, 
dermal fillers, X-rays, etc.
5.5.3
Recording
Previous and concomitant therapies are to be recorded on the Drugs/Therapies form 
(for drugs/therapies) and/or on the Medical and Surgical Procedures form (for medical/surgical 
procedures) in the eCRF.
Concomitant therapies are to be recorded, reviewed, and updated at each visit.
Any new concomitant therapy or modification of an existing therapy may be linked to an adverse 
event (AE). A corresponding Adverse Event Form must be completed to account for the change 
in therapy, except in some cases such as therapy used for prophylaxis, dose modification for a 
chronic condition, etc.
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5.5.4
Authorized concomitant therapies
Unless listed under the exclusion criteria (Section 5.4 item 7) or in prohibited concomitant 
therapies (see Section 5.5.5), all therapies are authorized.  
No other topical treatments, other than the test materials, will be permitted on the treated areas. 
However, emollients on healthy skin areas are permitted during the course of the study.  
Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin Cleanser or equivalents (provided by 
the Sponsor) may be used as needed, on non-treated areas of the skin.  
Subjects will be permitted to use medicated shampoos that do not contain corticosteroids or 
vitamin D derivatives to treat scalp psoriasis.  Tar products can be used on the face and 
scalp areas.
Topical anesthetic creams for the purpose of blood draw comfort may be used on non-treated 
areas and should be documented in the eCRF.
Sunscreen may be used as needed on non-treated areas of the skin.
Subjects taking oral calcium and vitamin D for prophylactic purposes must be on a stable dose 
for at least 4 weeks prior to screening and are not to exceed the Recommended Daily Allowance 
for calcium (1,300 mg for subjects aged 12-16 years and 11 months and 1,000 mg for subjects 
less than 12 years) or Vitamin D (600 IU). Subjects are to remain on the same dose throughout 
the course of the study.
5.5.5
Prohibited concomitant therapies
The following therapies are prohibited because they may interfere with the efficacy and/or safety 
(for example interaction with the study drug(s) metabolism) assessment of the study drug(s):

Listed in Section 5.4 item 7

Listed in Section 13.1, Appendix 1 – Unauthorized therapy
If prohibited therapies become a necessary treatment for the safety or best interest of the subject, 
GALDERMA must be notified to discuss possible alternatives prior to administration of a 
prohibited therapy.
If a subject receives prohibited therapy during the clinical trial, GALDERMA must be notified to 
discuss the pertinence and the modalities for the subject to continue in the clinical trial.
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5.6
Procedures/Reasons for subject discontinuation
An Investigator may decide to discontinue a subject from the clinical trial for safety reasons.
Although the importance of completing the entire clinical trial should be explained to the subject 
by the clinical trial personnel, any subject is free to discontinue his/her participation in this 
clinical trial at any time and for whatever reason, specified or unspecified, and without any 
prejudice.  No constraints are to be imposed on the subject, and when appropriate, a subject may 
be treated with other conventional therapy when clinically indicated. 
When a subject does not complete the clinical trial, he/she will be fully assessed, if such 
assessment is possible.  The procedures designated for the Week 26/Early Termination visit 
should be completed for all subjects discontinuing the clinical trial and the appropriate 
Case Report Form eCRF should be completed.  All discontinuations and the reason for 
discontinuation are to be documented by the Investigator on the Exit Form, and also on the 
Adverse Event Form for discontinuation due to an AE.
For discontinuation due to an AE, the Investigator should ensure that the subject receives suitable 
therapy for his/her AE.
Subjects who have a 2 grade worsening of their plaque psoriasis per the IGA scale, or who reach 
an IGA of 4, should be discontinued and complete the Week 26/ET visit. If the subject 
experiences complete clearing of psoriasis (IGA = 0), per physician assessment the subject 
should discontinue the study drug but continue to follow the visit schedule through the 
Week 26 visit.  Treatment with study drug should be resumed if the IGA score is 0 and 4. 
Subjects whose parathyroid hormone (PTH) results fall below the lower limit of normal will be 
assessed on a case-by-case basis; study drug application may be temporarily discontinued based 
on Sponsor and Investigator assessment. Serum PD parameters will be regularly checked (at least 
within 2 weeks) at Investigator’s and Sponsor’s discretion until the PTH level is back within the 
normal range.  In addition, the IDMC will be notified of all PTH results that decrease by 
30% from the subject’s baseline results and will recommend appropriate management of the 
subject on a case-by-case basis. 
For subjects whose parathyroid hormone (PTH) results have fallen below the lower limit of 
normal, if either:

The PTH does not return to the normal reference range within two weeks 
OR

The PTH returns to the normal reference range but falls below the lower limit of normal at 
any other stage during the course of the study
then the IDMC will be contacted for advice on management. 
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Subjects with abnormal serum albumin-adjusted calcium should temporarily discontinue study 
drug use immediately: The IDMC will be consulted for each occurrence of hypercalcemia, and 
depending on the severity and/or duration of the out-of-range serum calcium, will recommend 
appropriate management of the subject on a case-by-case basis in combination with other 
lab values and clinical condition of the subject in general.
Subjects with suspected kidney stones should temporarily discontinue study drug and will be 
referred to their Primary Care Physician (PCP) for care in tandem with Sponsor consultation of 
the IDMC. If urolithiasis is not confirmed, the subject may resume treatment with study drug.  
Subjects with confirmed urolithiasis should permanently discontinue study drug use and 
complete the Week 26/ET visit.
A subject who has been enrolled and assigned a kit number cannot be replaced by another 
subject if he/she discontinues the clinical trial for any reason.
For subjects not completing the entire study, all used (and unused) study drugs containers should 
be returned by the subject’s parent/legal guardian to the defined personnel at the study center. 
GALDERMA may also decide to prematurely terminate or suspend a subject’s participation in 
the clinical trial.
Potential reasons for discontinuation, as listed on the Exit Form, are defined below:
Pregnancy:
Withdraw the Subject from the clinical trial and follow the 
procedure described in Section 7.2.3.2.4
Lack of Efficacy:
Investigator judgment only: based on therapeutic/disease-state 
expectations.  If subject/parent or legal guardian opinion only, mark 
“subject request” and document it in the comment section of the eCRF 
Exit Form.
Adverse Event:
Complete an Adverse Event Form.
Subject Request:
Includes consent withdrawal, subject relocation, schedule conflicts. 
Explain the reason for withdrawal in the comment section of the eCRF 
Exit Form.
Protocol Violation:
Explain the violation in the comment section of the eCRF Exit Form.
Lost to Follow-up:
Confirmed with two documented phone calls and a certified letter 
(delivery receipt requested) without answer.  Explain in the comment 
section of the eCRF Exit Form.
Other:
This category is to be used for a subject who discontinues due to a 
reason other than as specified in the predefined categories above.  
Explain the reason for discontinuation in the comment section of the 
eCRF Exit Form.
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If reason for discontinuation is “subject or parent/legal guardian request” or “other”, the subject 
or parent/legal guardian will be questioned to rule out the possibility of an AE and the response 
will be documented in source documentation.
6
CLINICAL SUPPLIES
6.1
Clinical supply identification and use
6.1.1
Study drug(s) description
Table 3
Description and usage of the study drug(s)
Investigational product
Trade Name or Equivalent
Vectical/ Silkisointment
Name of Drug Substance  
calcitriol 
Internal Code 
CD2027
Pharmaceutical Form
ointment
Concentration
3 mcg/g
Formula number
0100/B50100
Packaging (type and size)
Aluminum Tube 100 g
Storage Conditions
Store at 25° C (77° F); excursions permitted to 15° -30° C 
(59°-86° F) Do not freeze or refrigerate.
Dosage (total daily dose)
Maximum of 0.5 g/kg of body weight or 28 grams daily 
(whichever is the lower)
Route
Topical to psoriatic skin
Dose Regimen 
Twice daily application (morning and evening)
Duration of administration
26 weeks
Location of Treated Area
Psoriatic skin (excluding face and scalp)
6.1.2
Subject Identification Number (SIN) 
Upon signature of the ICF, each subject will be assigned a Subject Identification Number (SIN) 
allocated in ascending sequential order for each subject without skipping any number.
For the duration of the entire clinical trial, the subject will be identified by the SIN for all 
documentation and discussion.
One re-screening is allowed.
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6.1.3
Method of treatment assignment
All qualified subjects will receive the study drug.  All enrolled subjects will be assigned a kit 
number using the Interactive Response Technology (IRT) system.
No randomization will be performed for this study.
6.1.4
Kit number/randomization number
Kit numbers will be assigned according to a pre-specified drug kit list.
No randomization numbers will be assigned.
6.1.5
Instructions for use and administration
The first dose will be applied under the supervision of the Investigator, at the Investigative site.
Application should be done either by the subject’s parent / legal guardian or by the subject 
himself. It is the responsibility of the parent/legal guardian to decide if the subject can apply the 
product himself and if they should supervise the application depending on the capability of the 
child. After application, the study product tube should be stored out of the reach and the sight of 
children,
Application will consist of a thin film of study drug as needed to cover all involved areas twice 
daily (morning/evening), without exceeding a maximum of 0.5 g/kg of body weight or 28 g daily 
(whichever is the lower).  The dosing calendar is to be completed by the subject or subject’s 
parent or legal guardian daily and returned to the site at each visit.
For the subset of subjects with PK evaluations, the drug product MUST NOT be applied on the 
areas that will be used for blood sampling. These areas will be defined at screening by the 
Investigator.
In addition, at the week 4, week 12 and week 26 visits, study drug applications will be performed 
on site after the PK pre-dose blood sampling is obtained.  This blood sample has to occur 
12 hours (1 hour) after the last product application.
To avoid potential contamination of the blood sample collected, study drug applications and 
blood draws must NOT occur in the same room. Additionally, the blood draw area should be 
clean and kept away from contact with study drug. 
Subjects should wait at least six hours after the study treatment application before swimming or 
bathing.  
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Cetaphil® Moisturizing Cream or equivalent (provided by the Sponsor and distributed by the 
Investigator or designee at the Baseline Visit) may be used during the study as needed on 
non-treated areas of the skin. Cetaphil® Gentle Skin Cleanser or equivalent (provided by the 
Sponsor) may be used for cleansing.
Subjects will be permitted to use medicated shampoos that do not contain corticosteroids or 
vitamin D derivatives to treat scalp psoriasis.  Tar products can be used on the face and 
scalp areas.
No other topical treatments, other than the test materials, will be permitted on the treated areas. 
However, emollients and sunscreen on healthy skin areas are permitted during the course of the 
study.
Dietary instructions: subjects will be asked to maintain the same dietary habits, especially 
calcium intake as before the study.  Subjects should maintain adequate hydration. Detailed 
instructions will be provided to the subjects regarding appropriate hydration in the subject 
instructions document.
It is recommended that the subject use protective clothing and other measures/precautions to 
protect themselves from excessive sun exposure while participating in this study.  
Subjects and parents/legal guardians should wash their hands after each application of 
study drug.
6.1.6
Other supplies
Adequate supplies of the following items are to be provided to or sourced by each study site:

Urinary pregnancy tests

Cetaphil® Moisturizing Cream & Cetaphil® Gentle Skin Cleanser (or equivalents)
Note: Cetaphil® Moisturizing Cream or equivalent may be used during the study as needed on 
non-treated areas of the skin.  
All unused UPTs and undispensed Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin 
Cleanser or equivalents, etc. are to be returned to the Sponsor, or sponsor’s contract vendor for 
destruction.
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6.2
Study drug(s) packaging and labeling
Kits will be dispensed at the following visits: Baseline (1 kit), Week 4 (2 kits), and 
Week 12 (4 kits) Each kit will contain 8 100-gram tubes.   
The labels will be printed in the languages of participating countries.  Labels will contain the 
information requested by Good Manufacturing Practice, local regulation, kit number and 
corresponding Week/Visit number.
The labeling will be performed under the responsibility of Galderma R&D, LLC, following the 
ICH Guidelines.  
6.3
Supplies management
6.3.1
Accountability
Upon receipt of the study drug(s), the Investigator or designee will maintain accurate records of 
the study drug(s) delivery to the clinical trial center using the IRT system. The inventory at the 
clinical trial center, the use by each subject, the reconciliation of all study drug(s) received from 
the Sponsor, and the return to the Sponsor or alternative disposal of used and unused study 
drug(s) will also be tracked in the IRT system.
The Investigator or designee is required to sign the original “Acknowledgement of Receipt of 
Clinical Supplies” Form (or any acknowledgment of receipt) upon receipt and inspection of the 
supplies, fax the signed copy to the shipping depot and retain the receipt within the clinical trial 
file.
All used and unused clinical study drug(s) will be appropriately inventoried by the monitor and 
returned to the Sponsor, or sponsor’s contract vendor for reconciliation, counting and destruction 
as instructed by GALDERMA/CRO.
All clinical study drug(s) sent to the Investigator/Institution will be accounted for and 
no unauthorized use is permitted.
6.3.2
Storage of clinical study drug(s)
Study drug(s) must be stored in a safe and secure area with restricted access, under the storage 
conditions specified by GALDERMA (see Table 3).
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6.3.3
Dispensing and return 
The Investigator or designee is responsible for dispensing study drug in accordance with the 
protocol at the Baseline, Week 4 and Week 12 visits.  Study drug will only be dispensed to 
subjects’ parent/legal guardian in accordance with the conditions specified in the protocol.
Each subject kit will contain:

8 tubes of calcitriol 3 mcg/g ointment to be dispensed  
All kits are to be numbered.  The kit number is to be recorded in the eCRF.  Dispensation and 
return of test material at each visit, is to be appropriately documented by the designated study 
personnel.  Each subject’s parent/legal guardian is to return all dispensed study tubes at each visit 
as appropriate.
Each subject’s parent/legal guardian will receive the initial study drug supply at the Baseline 
visit and additional supplies at each interim visit.  All study drug containers must be inventoried 
and a record of the dispensing and return of each container for each subject must be 
appropriately documented by the Investigator or designee using the IRT system.  Requirements 
of all study drug returns will be reinforced for all subjects at each visit during the study. 
Any dispensing errors must be reported to the Sponsor/CRO and properly documented in the 
eCRF and source documentation.
Subject’s parent/legal guardian will be instructed to return the study drug in order to have new 
study drug dispensed and the process will be repeated throughout the subject’s participation.  
However, the study drug may be dispensed even if all tubes from previous visits are not returned, 
but the subject’s parent/legal guardian will be instructed on the importance of returning the tubes 
prior to receiving further supplies.
Subjects/Subject’s parents/legal guardians will be instructed by the Investigator or designee on 
the importance of being compliant with the use of the study drug(s) throughout the clinical trial 
but also about the importance of returning their study drug(s) (used and/or unused) at each visit.
All used and unused study drug tubes are to be returned to the Sponsor, or sponsor’s contract 
vendor. 
In the event of early termination/suspension of the clinical trial, a rapid recall of study drug(s) 
will be initiated.  The Investigator or designee must immediately instruct the subjects to stop the 
study drug(s) regimen and return the study drug(s) to the clinical trial center.
For subjects who do not complete the entire clinical trial, all used and unused study drug(s) 
should be returned by the subjects to the defined personnel at the clinical trial center.
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6.3.4
Treatment compliance management and record
Subjects / Subjects’ parents/legal guardians will be required to fill out a dosing calendar to 
collect the date and time of each application and to bring back this dosing calendar at each visit. 
Upon study product return, the study staff will check the dosing calendar and the returned 
products. In case of bad compliance or missed applications, the study staff will re-instruct the 
subject / Subjects’ parents/legal guardians on the proper use.
6.4
Dose modification 
Temporary drug discontinuations and dose modifications may be permitted in instances of out-
of-range laboratory results, local tolerability issues, and clearing/worsening of disease.  
Subjects whose PTH results fall below the lower limit of normal will be assessed on a 
case-by-case basis; study drug application may be temporarily discontinued based on Sponsor 
and Investigator assessment. Serum PD parameters will be regularly checked (at least within 
2 weeks) at Investigator’s and Sponsor’s discretion until the PTH level is back within the normal 
range (see section 5.6). 
Subjects with abnormal serum albumin-adjusted calcium should temporarily discontinue study 
drug; the IDMC will recommend appropriate management of the subject on a case-by-case basis. 
Subjects with other out-of-range laboratory results may temporarily discontinue study drug 
dosing until the issue resolves according to Investigator or IDMC discretion. 
Subjects with suspected urolithiasis should temporarily discontinue study drug.  If urolithiasis is 
not confirmed, the subject may resume treatment with study drug.  Subjects with confirmed 
urolithiasis should permanently discontinue study drug use and complete the Week 26/ET visit.
Dose modifications (i.e. dosing only once a day) will also be permitted for skin tolerability issues 
according to Investigator discretion. Dose modifications may be made for up to 7 consecutive 
days and must be documented in the subject source document.  In case of study drug dosage 
modification, an earnest attempt should be made to return the subject to a twice daily treatment 
regimen as soon as possible. Increasing the dose above 0.5 g/kg of body weight or 28 g/day is 
strictly prohibited. 
Subjects who have a 2 grade worsening of their plaque psoriasis per the IGA scale, or who reach 
an IGA of 4, should be discontinued and complete the Week 26/ET visit.  If the subject 
experiences complete clearing of psoriasis (IGA = 0), per physician assessment the subject 
should discontinue the study drug but continue to follow the visit schedule through the 
Week 26 visit. Treatment with study drug should be resumed if the IGA score is 0 and 4. 
Two temporary study drug discontinuations or dose modifications are allowed and must be 
documented in the subject source documents. Additional study drug discontinuations or dose 
modifications must be discussed with the Sponsor. 
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6.5
Blinding
6.5.1
Verification of blinding
Not applicable to this study.
6.5.2
Unblinding during the clinical trial
Not applicable to this study.
7
CLINICAL TRIAL ASSESSMENT
7.1
Efficacy assessments
7.1.1
Efficacy measurements
IGA and Pruritus evaluations will be assessed at each visit on all treated areas.  
7.1.1.1
IGA (as evaluated on all treated areas by a Board Certified (or any other 
regional equivalent) Dermatologist)
The IGA will be evaluated at each visit on a 0 to 4 point scale. The following definitions will be 
used to score IGA:
0
Clear
No signs of psoriasis except for residual hypopigmentation / 
hyperpigmentation
1
Almost Clear
Just perceptible erythema, no induration, and no scaling
2
Mild
Mild erythema, no induration, and mild or no scaling
3
Moderate
Moderate erythema, mild induration, and mild or no scaling
4
Severe
Severe erythema, moderate to severe induration, and scaling of any 
degree
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7.1.1.2
Pruritus (as evaluated on all treated areas)
Pruritus will be evaluated at each visit and scored on a 0 to 4 point scale. The following 
definitions will be used to score Pruritus:
Pruritus: an itching sensation.
0
None
No itching
1
Mild
Slight itching, not really bothersome
2
Moderate
Definite itching that is somewhat bothersome without loss of sleep
3
Severe
Intense itching that has caused pronounced discomfort, night rest 
interrupted
4
Very Severe
Very severe itching that has caused pronounced discomfort during the 
night and daily activities
7.1.1.3
Other Assessments:
Percent Body Surface Area (BSA) involved will be assessed using the methodology shown in 
Section 13.3, Appendix 3.
7.1.2
Efficacy endpoints
Percentage of subjects with an IGA Score of 0 (clear) or 1 (almost clear).
Change from Baseline in Pruritus  
Change from Baseline in % BSA 
7.2
Safety assessment
A safety assessment will be conducted for all subjects at the screening visit (from the Informed 
consent signature) and every subsequent visit.  The safety parameters are AEs, (to be recorded as 
specified in Section 7.2.3), laboratory safety tests, physical examination, and vital signs.
All abnormal findings at the screening visit identified as clinically significant by the Investigator, 
will be recorded in the Medical History form.  For any clinically significant changes from the 
screening visit, an AE is to be recorded.
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7.2.1
Physical examination and vital signs
7.2.1.1
Physical examination
The following body systems should be evaluated as “normal” or “abnormal” by the Investigator, 
at the visits per the Schedule of Assessments (Table 2):
Skin
Cardiovascular system
Respiratory
Abdomen
Head and neck
Musculoskeletal system
Neurological function (mental status exam [level of consciousness, cognitive function], 
cranial nerve assessment, reflex testing, motor system assessment, sensory system 
assessment)
Lymph nodes
Psychological
Weight will be recorded every time a physical examination is performed and height will be 
evaluated at Screening Visit only.
The Investigator may choose to further investigate any other sign that he/she observes during the 
physical examination.
7.2.1.2
Vital signs
Evaluation of vital signs (blood pressure and pulse rate) will be performed after 5 minutes rest in 
sitting position.  It will include measurement of systolic and diastolic blood pressure and pulse 
rate in the sitting position.
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7.2.2
Laboratory safety tests
The following laboratory safety tests will be performed according to the Schedule of 
Assessments (Table 2). 
Hematology:
White blood cell (WBC) count with differential, red blood cell (RBC) count, hemoglobin (Hb), 
hematocrit (hct), mean cell volume (MCV), and platelet count (Plt)
Blood chemistry (non-fasting):
Total protein, alanine aminotransferase (ALT) (SGPT), aspartate aminotransferase (AST) 
(SGOT), alkaline phosphatase (ALP), blood urea nitrogen, creatinine (calculated creatinine 
clearance), and bilirubin (total and conjugated).
The Principal Investigator or another medically qualified Investigator must review and evaluate 
laboratory values for each subject in a timely manner.  The Investigator will initial and date each 
laboratory report and note directly on the report whether or not each out-of-range laboratory 
value is clinically significant.
For each out-of-range laboratory result, the Investigator will enter in the eCRF the Investigator 
judgment on the presence or the absence of a clinical significance.
All out-of-range laboratory values at screening, identified as clinically significant by the 
Investigator, will be recorded in the medical history (report a diagnosis rather than individual 
laboratory parameters abnormality whenever possible).
All out-of-range laboratory values after screening, are to be assessed for clinical 
significance by the Investigator (physician) or another medically qualified Investigator and 
to be reported as an AE if both of the following conditions are met:
The abnormality suggests a disease and/or organ toxicity, and/or is considered pathological
AND
This abnormality was not present at the screening visit or is assessed as having worsened since 
the screening visit.
Unscheduled visits may occur due to laboratory result(s) that warrant further testing.  If the 
Investigator observes a clinically relevant laboratory test value, the laboratory tests will be 
repeated as soon as possible and monitored until the values have returned to normal and/or an 
adequate explanation for the abnormality is found. This does not apply to screening laboratory 
test values. 
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An out-of-range laboratory value that is identified as clinically significant and related to the 
study drug(s) is considered by the Sponsor to be an Adverse Event of Special Interest (AESI) 
(see Section 7.2.3.1.3).
For AEs and AESIs, whenever possible, the Investigator is to provide a diagnosis rather than to 
report individual laboratory abnormalities.
A summary of sample
volumes and the number of blood samples is detailed in 
Section 13.2, Appendix 2.
Urinalysis:
A semi-quantitative urinalysis will be performed.  The following parameters will be evaluated: 
glucose, ketones, blood, proteins, leukocytes, and nitrites. 
Pharmacodynamic parameters:
Serum (non-fasting): calcium, phosphorus, albumin (in order to calculate the serum 
albumin-adjusted calcium), PTH
Urine: Calcium and creatinine (in order to calculate urine calcium:creatinine ratio) on 
24-hour urine collections, when feasible, or fasting (4 hour) urine samples.  Subjects that are 
toilet-trained should be actively encouraged to complete the 24-hour urine collection.  In case of 
Ca:Cr ratio above the normal range on a urine sample after fasting for 4 hours, the measurements 
should be repeated on a 24–hour urine collection whenever possible.
Other Assessments

1, 25(OH)2D 

25(OH)D 
Urine Pregnancy Test
Post menarcheal female subjects of childbearing potential will have a urine pregnancy test 
performed at all visits.  Additional urine pregnancy tests may be performed at the 
Investigator’s discretion.
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For pre-menstrual subjects who begin menses after the Screening visit, pregnancy tests will be 
performed according to the Schedule of Assessments (Table 2) for females of childbearing 
potential (Baseline, Week 4, Week 12, Week 26/ET, and Week 30). In addition, subjects must 
adhere to the contraceptive methods as outlined in Inclusion Criteria 7. 
The screening visit laboratory values must be available prior to the Baseline visit.
7.2.2.1
IDMC Case Management
The management of hypercalcemia and PTH-suppressed cases will remain under the 
responsibility of the IDMC.
All cases of hypercalcemia, confirmed urolithiasis, out of range PTH levels or decreases in 
PTH of 30% from the subject’s Baseline visit will be communicated immediately to the Principal 
Investigator, to Clinical Safety Officer (see contact detail in section 7.2.3.2.2), and to the 
IDMC members as alerts, as appropriate.  Galderma will receive recommendations from the 
IDMC on the management of the subject and on the study outcome.
Subjects with microscopic or macroscopic hematuria will be managed according to Investigator 
discretion. The IDMC will be notified of cases of hematuria as necessary.  Management of 
subjects with suspected urolithiasis will be handled on a case by case basis.  Subjects with 
suspected urolithiasis should temporarily discontinue study drug.  If urolithiasis is not confirmed, 
the subject may resume treatment with study drug.  Subjects with confirmed urolithiasis should 
permanently discontinue study drug use and complete the Week 26/ET visit.
7.2.3
Adverse Events
Adverse events (AEs) are to be monitored throughout the course of the clinical trial.  All AEs are 
to be reported on the Adverse Event Form of the eCRF with complete information as required. 
If AEs occur, the main concern will be the safety of the subjects.  At the time of the 
ICF signature, each subject must be provided with the name and phone number of clinical trial 
center personnel for reporting AEs and medical emergencies.
The subject’s parent / legal guardian or subject (according to subject’s maturity level), should be 
asked specifically about symptoms of kidney stones e.g. obvious hematuria or pyuria, or vague 
abdominal or flank pain/discomfort, or possible pain radiating to the groin area at each 
study visit.
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7.2.3.1
Definitions
7.2.3.1.1
Adverse events (AE)
According to ICH E2A, an AE is any untoward medical occurrence in a subject or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have 
a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory value), symptom, or disease temporally associated with 
the use of a medicinal (investigational) product, whether or not related to the medicinal 
(investigational) product.
Thus any new sign, symptom or disease, or any clinically significant worsening of an existing 
sign, symptom or disease compared to the condition at the first visit (including disease treated), 
should be considered as an AE.  Lack of efficacy is not considered as an AE.
Each new episode of a chronic disease (e.g., hay fever, allergy, etc) should be reported as a 
new AE.
Notes:

Any new sign or symptom reported by the subject that appears after accidental or 
intentional overdose or misuse should also be reported as an AE.

There should be an attempt to report a diagnosis rather than the signs, symptoms or 
abnormal laboratory values associated with the report of an AE.  However, a diagnosis 
should be reported only if, in the Investigator’s judgment, it is relatively certain. 
Otherwise, symptoms, signs, or laboratory values should be used to describe the AE.

Pregnancy is not to be considered as an AE; however, is an important medical event that 
must be monitored as described in Section 7.2.3.2.4.
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7.2.3.1.2
Serious Adverse events (SAE)
An SAE is any untoward medical occurrence that at any dose:

Results in death,

Is life-threatening,

Requires inpatient hospitalization or prolongation of existing hospitalization,

Results in persistent or significant disability/incapacity, or

Is a congenital anomaly/birth defect.
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the safety of the subject, and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasia, or 
convulsions that do not result in hospitalization.
Note:
The term “life-threatening” refers to an event in which the subject was at risk of death at the time 
of the event; it does not refer to an event that hypothetically might have caused death if it was 
more severe.
Inpatient hospitalization is considered to have occurred if the subject has had to stay for a night 
at the hospital.  The criterion for prolongation of hospitalization is also defined as an extra night 
at the hospital.  Hospitalization may not constitute sufficient grounds to be considered as an 
SAE if it is solely for the purpose of a diagnostic tests (even if related to an AE), elective 
hospitalization for an intervention that was already planned before subject enrolment in the 
clinical trial, admission to a day-care facility, social admission (e.g., if the subject has no place to 
sleep), or administrative admission (e.g., for a yearly examination).
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7.2.3.1.3
Adverse Events of Special Interest (AESIs)
An AESI is a noteworthy event for the particular study drug that can be appropriate to monitor 
closely. It could be serious or non-serious and AESIs could include events that might be potential 
precursors or prodromal symptoms for more serious medical conditions in susceptible 
individuals.
AEs of special interest for this study are defined as:
1.
Typical clinical signs and symptoms consistent with Vitamin D toxicity: 

polyuria, polydipsia 

clinically significant mental status changes
2.
Out-of-range laboratory result that is identified as clinically significant and related to the 
study drug
3.
Dermatological events such as severe skin irritation as well as severe local and/or 
generalized pruritus
4.
Suspected skin sensitization (contact allergy)
5.
Cutaneous AE assessed as related to the study drug and leading to discontinuation of the 
study drug, including temporary discontinuations 
For AESIs, the Investigator is required to complete the Adverse Event Form on the eCRF and 
follow the AESI reporting procedures in Section 7.2.3.2.3 even if the event is considered 
non-serious according to the usual regulatory criteria.
7.2.3.1.4
Unexpected adverse drug reaction
According to ICH E6, an unexpected adverse drug reaction is defined as an adverse reaction, the 
nature or severity of which is not consistent with the applicable study drug information 
(e.g., Investigator’s Brochure for an unapproved investigational product or the package 
insert/summary of product characteristics for an approved product).
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7.2.3.1.5
Adverse event reporting period
The clinical trial period during which AEs must be reported is the period from when the subject 
signed the Informed Consent Form to the end of the subject’s participation.
The Sponsor should be informed if the Investigator becomes aware of any unusual safety 
information or any safety information that appears to be drug-related involving a subject who has 
participated in a clinical trial, even after a subject has completed the clinical trial.  
The Investigator should be diligent in looking for possible latent safety effects that may not 
appear until a medication has been discontinued.
7.2.3.1.6
Severity
Severity is a clinical determination of the intensity of an AE and not of a disease.
The Investigator is to classify the intensity of AEs using the following definitions as a guideline 
for all AEs occurring during clinical trials conducted or sponsored by GALDERMA. For this 
classification, the Investigator will take into account the possible range of the intensity of the 
event and report the grade of intensity which is the most appropriate according his medical 
judgment.
Mild
Awareness of signs or symptom, but easily tolerated.
Moderate
Discomfort, enough to cause interference with usual activity
Severe
Incapacitating with inability to work or perform usual activity
7.2.3.1.7
Relationship to the study drug(s)
The Investigator is to determine whether there is a reasonable causal relationship between the 
study drug(s) and the AE.  Medical judgment should be used to determine the relationship, 
considering all relevant factors including the pattern of reaction, temporal relationships, positive 
dechallenge or rechallenge, relevant medical history, and confounding factors such as 
co-medication or concurrent diseases.
The expression “reasonable causal relationship” is meant to convey in general that there are facts 
or arguments to suggest a causal relationship (ICH E2A, Section IIIA 1).  
The relationship assessment for an AE is to be completed using the following definitions as a 
guideline for all AEs occurring during clinical trials conducted or sponsored by GALDERMA:
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Reasonable possibility:
According to the reporting Investigator, there is a reasonable possibility (i.e., suggestive 
evidence or arguments) that there is a causal relationship irrespective of the dose administered 
between:

The study drug (investigational product, active comparator, or placebo/vehicle, etc.) and 
the AE, 

The clinical trial protocol procedure (such as UV-induction, biopsy, xylocaine injection, 
blood test or intraocular pressure measurement, etc) and the AE.
No Reasonable Possibility:
No suggestive evidence or arguments can be identified regarding a causal relationship between 
the study drug or the clinical trial protocol procedure and the AE.
7.2.3.2
Reporting procedures
7.2.3.2.1
Procedures for reporting Adverse Events
The collection of AEs is from the time that a subject signs the ICF to their final visit.
At each post-enrollment visit, the Investigator (or sub-Investigator) will question the subject 
about AEs using an open non-persuasive question to elicit reporting of AEs, for example 
“Have you noticed any change in your health since the last visit?”  Directed questioning and 
examination will then be performed as appropriate. 
Any AE occurring during the AE reporting period, whether it is related to the study drug(s) or 
not, will be recorded immediately in the source document, and described on the Adverse Event 
Form of the eCRF along with the date of onset, severity, relationship to the study drug(s), and 
outcome, without omitting any requested and known information.  Additional information may 
be requested under certain circumstances.  Adverse Events (AEs) assessed as related to the 
treatment will be monitored until they are completely or satisfactorily resolved.  Other AEs will 
be monitored until the last visit if they are not resolved or satisfactorily resolved.
The Investigator will obtain and maintain in the subject’s files all pertinent medical records, 
information and medical judgment from colleagues who assisted in the treatment and follow-up 
of the subject.  If necessary, the Investigator will contact the subject’s personal physician or 
hospital staff to obtain further details.
For SAEs (see Section 7.2.3.2.2), AESIs (see Section 7.2.3.2.3), cases of urolithiasis and 
pregnancies (see Section 7.2.3.2.4), the CSO is to be informed immediately by e-mail/fax.  
The event must be reported by fax or sent by e-mail to the CSO within 24 hours of receipt of the 
information (contact details in Section 7.2.3.2.2).
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7.2.3.2.2
Procedure for reporting a Serious Adverse Event
For an SAE occurring during the period of the clinical trial, regardless of whether it is related to 
the treatment or not, and of whether it is expected or not, the Investigator must do the following:
1.
Take prompt and appropriate medical action, if necessary.  The safety of the subject is the 
first priority.
2.
Immediately inform the CSO of the event by e-mail or by fax and discuss further actions to 
be taken.
Clinical Safety Officer
For North America: Phone: (+1) (609) 235-6035 - Fax: (+1) (609) 228-6153 
E-mail: pharmacovigilance@galderma.com
For EU: Phone: +33 (4) 92 95 29 69 – Fax: +33 (4) 93 95 70 92
E-mail: pharmacovigilance@galderma.com
For regions outside of North America and the EU, a Clinical Safety Officer will be designated as 
necessary.  Additional contact details are provided in the Investigator’s site file.
3.
Complete the Adverse Event Form provided in the eCRF as fully as possible.
4.
Ensure that the event is classified as an SAE.
5.
Print and complete the Serious Adverse Event Form (available in the EDC system as PDF 
document).  Fax or scan and send by e-mail the completed form, accompanied by any other 
relevant information or medical records (e.g., laboratory test results) within 24 hours of 
receipt of the information to the GALDERMA CSO. The demographics, medical history, 
previous and concomitant therapies, and adverse event pages of the eCRF must be 
completed and available for review in the EDC system at the time of the report.
6.
Monitor and record the progress of the event until it resolves or reaches a clinically stable 
outcome, with or without sequelae.  For all additional follow-up evaluations, fax or scan 
and send by e-mail all additional follow-up information to the GALDERMA CSO within 
24 hours of receipt of the updated information.  Serious Adverse Events (SAEs) will be 
monitored until the Investigator and Sponsor agree that the event is satisfactorily resolved.
7.
Obtain and maintain in his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of the subject.  
If necessary, contact the subject’s personal physician or hospital staff to obtain further 
details.
8.
Inform the CSO of the final outcome of the event.  Send a revised or updated Serious 
Adverse Event Form and Adverse Event Form, if appropriate.
9.
Comply with the applicable regulatory requirement(s) related to the reporting of SAEs to 
the Institutional Review Board (IRB) / Independent Ethics Committee (IEC).
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7.2.3.2.3
Procedure for reporting an Adverse Event of Special Interest
For any AESI (see Section 7.2.3.1.3) occurring during the period of the clinical trial, whether 
related to the treatment or not, and whether expected or not, the Investigator is to do the 
following:
1.
Take prompt and appropriate medical action, if necessary.  The safety of subjects is the 
first priority.
2.
Immediately inform the CSO by e-mail or fax of the event. 
3.
Investigator contact: Refer to Section 7.2.3.2.2
4.
Complete the Adverse Event Form provided in the eCRF as fully as possible.
5.
Ensure that the event is classified as an AESI.
6.
Print the Adverse Event form. Fax or scan and send by e-mail the completed form, 
accompanied by any other relevant information or medical records (e.g. laboratory test 
results) within 24 hours of receipt of the information to the GALDERMA CSO. The 
demographics, medical history, previous and concomitant therapies, and adverse event 
pages of the eCRF must be completed and available for review in the EDC system at the 
time of the report.
7.
Monitor and record the progress of the event until it resolves or reaches a clinically stable 
outcome, with or without sequelae.  For all the additional follow-up evaluations, first 
inform the CSO of the outcome by fax or send the additional follow-up information by 
e-mail to the GALDERMA CSO within 24 hours of receipt of the updated information. 
AESIs will be monitored until the Investigator and Sponsor agree that the event is 
satisfactorily resolved. 
8.
Obtain and maintain in his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of the subject.  
If necessary, contact the subject’s personal physician or hospital staff to obtain further 
information such as anonymized medical records.
9.
Inform the CSO of the final outcome of the event.  Send a revised or updated Adverse 
Event Form, if appropriate.
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7.2.3.2.3.1
Procedure for suspected sensitization (Challenge and Rechallenge Patch 
Test procedures)
If a subject experiences a suspected skin sensitization (contact allergy), follow this procedure to 
characterize the event: 
1.
Stop the study drug
2.
Document the event as an AESI, phone the CSO immediately and report the event 
within 24 hours as described in Section 7.2.3.2.2.
3.
After all signs and symptoms have resolved (after a minimum of two weeks), perform a 
re-challenge with the assigned study drug.
4.
Apply the assigned study drug to a naive area on the back (approximately 1 inch in 
diameter, 2.54 cm) and cover it with non-occlusive gauze (dressing) for 48 hours.  
5.
After 48 hours, remove the gauze and evaluate the site:

at approximately 15 to 30 minutes (1st reading) and,

at 48 hours (2nd reading) .  

A facultative 3rd reading must be performed at 96 or 120 hours after removal of the gauze 
if the second reading is equivocal.  
Duration of study 
drug application
1st Reading
2nd Reading
3rd Reading
48 hours
15 to 30 minutes
(after gauze removal)
48 hours
(after gauze removal)
96 or 120 hours
(after gauze removal)
6.
Use the following numerical (0 to 4) grading system at each reading: 
0
No reaction
No reaction
1
Mild erythema
Slight redness
2
Moderate erythema
Definite redness easily recognized
3
Severe erythema OR erythema with edema
Intense redness or redness associated with local swelling
4
Erythema with vesicles or erosion or bullae
Redness with small or large blisters or skin abrasion (can be 
accompanied by weeping/oozing, crusting)
7.
At last reading, the investigator will provide an assessment regarding a possible 
sensitization reaction using the following scale:
Sensitization Reaction
0
Negative (might include an irritative reaction)
1
Equivocal
2
Positive
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8.
Report the results from the re-challenge test as directed by the sponsor and document with 
photographs.
9.
If the re-challenge is negative, the subject may resume treatment.
10.
If the re-challenge is positive or equivocal, notify the CSO immediately and initiate a skin 
sensitization patch test as directed by the sponsor (with the study drug and possibly 
individual ingredients) after an additional 2 weeks and after all signs and symptoms have 
resolved. Follow the same procedure for the patch test as for the rechallenge.
7.2.3.2.4
Procedures for reporting pregnancies
Any pregnancy occurring during clinical trials, where the fetus could have been exposed to the 
study drug(s), must be monitored until its outcome in order to ensure the complete collection of 
safety data on GALDERMA products.
If a subject becomes pregnant, the Investigator is to do the following:
1.
Withdraw the subject from the clinical trial.
2.
Complete the Pregnancy Surveillance Form – Part I: History and Start of Pregnancy, 
provided by the CRA at the beginning of the clinical trial, as fully as possible.  Fax or send 
by e-mail this pregnancy form along with the Exit Form within 24 hours of receipt of the 
information to the GALDERMA CSO.
3.
Monitor and record the progress of the pregnancy until its outcome.  Contact the subject’s 
regular physician (general practitioner or gynecologist) or hospital staff to obtain further 
details and ask regular follow-up information.
4.
Inform the GALDERMA CSO of the progress by tri-monthly updates until the final 
outcome of the pregnancy.  For all the additional follow-up evaluations, fax or send by e-
mail the additional follow-up information to the GALDERMA CSO within 24 hours of 
receipt of the information.  If the subject can no longer be reached (lost to follow-up), 
documentation of the non-response/contact with two phone calls and a letter (certified with 
return receipt) is required.
5.
At the outcome of the pregnancy, complete the Pregnancy Surveillance Form – Part II: 
Course and Outcome of Pregnancy, as fully as possible.  Inform the CSO by e-mail/fax, 
then fax or send by e-mail this pregnancy form to the GALDERMA CSO within 24 hours 
of receipt of the information.
6.
If the pregnancy leads to an abortion (voluntary abortion, spontaneous abortion, or 
therapeutic abortion), in utero death or congenital anomaly, follow the procedure for 
declaration of an SAE (see Section 7.2.3.2.2).
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7.3
Pharmacodynamic assessments
The following Pharmacodynamic assessments will be performed according to the Schedule of 
Assessments (Table 2):
Serum (non fasting): calcium, phosphorus, albumin (in order to calculate the serum 
albumin-adjusted calcium), PTH. 
Urine: Urine calcium and creatinine on 24-hour urine collection, whenever possible, or 
a urine sample after fasting for 4  hours in order to calculate Urine calcium : creatinine 
ratio. Subjects that are toilet-trained should be actively encouraged to complete the 
24-hour urine collection. 
7.4
Pharmacokinetic assessment
7.4.1
Blood sampling
The systemic level of calcitriol will be assessed at each visit using a single blood sample (Ct) 
according to the Schedule of Assessments (Table 2). To avoid tube contamination, drug product 
application and blood draws have to be performed in different rooms. Blood samples will have to 
be collected in either the morning or evening (to be determined at screening according to the 
subject’s lifestyle). In addition, for the blood samples to be drawn during the treatment period 
(i.e. at Week 4, Week 12 and Week 26), the sampling has to occur 12 hours (1 h) after the last 
product application. Blood sampling procedure and handling of samples will be described in a 
separate document.
7.4.2
Plasma concentrations
Calcitriol plasma concentrations will be determined using an appropriately validated method by 
the sponsor or its representative. A bioanalytical protocol describing the details of the 
bioanalytical process will be written prior to the samples assays to specify the method and the 
acceptance criteria that will be used for the bioanalytical part of the study. The results will be 
described in a bioanalytical report which will be included in the Clinical Study Report (CSR).
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7.4.3
Pharmacokinetic measurements
The pharmacokinetic analysis will be carried out by GALDERMA R&D, Sophia Antipolis, 
France. The Ct mean values and the standard deviation (SD), will be calculated and reported. 
Assessments occurring at screening and baseline (before product application) will allow 
determining calcitriol endogenous levels variability. Pre-dose samples performed at Weeks 4, 12, 
and 26 will document the calcitriol plasma concentration during the treatment period. Blood 
sample drawn at week 30 visit allow determining the calcitriol plasma concentration one month 
after the last drug product application.
7.5
Other assessments
Percent Body Surface Area (BSA) involved will be assessed at each visit using the methodology 
shown in Section 13.3, Appendix 3.
7.6
Appropriateness of measurements
The measurements used in this study are based on the pivotal Phase 3 studies, completed in 
2002, confirming safety and efficacy of calcitriol 3 mcg/g ointment in adult subjects.  
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8
CLINICAL TRIAL VISITS DESCRIPTIONS AND PROCEDURES
8.1
Description of clinical trial visits
Please refer to the Schedule of Assessments table in the Synopsis (Table 2).
A written, signed ICF, Assent form for minors, and HIPAA/PIPEDA authorization must be 
obtained prior to performing any clinical trial-related evaluations and/or procedures.
8.1.1
Screening visit
1.
Review and explain the nature of the study to the subject (to the extent of his/her maturity) 
and to the subject’s parent/legal guardian and record this process in the subject’s file.
2.
If capable to give assent to decisions about participation in research, subject may sign an 
Assent Form to participate but must also have a parent or guardian sign the Informed 
Consent Form and HIPAA or PIPEDA (as appropriate) form at Screening visit prior to any 
study related procedures being performed. Provide the parent/legal guardian with a signed 
copy of each.
3.
Assign a subject identification number using the IRT system (Section 6.1.2).
4.
Verify inclusion/exclusion criteria.
5.
Ask the subject’s parent/legal guardian or subject (according to subject’s maturity level) 
about previous therapy/procedures, concomitant therapy/procedures, demography and 
medical history including the history of psoriasis (date of psoriasis onset, previous 
treatment, success of treatment).
6.
For post menarcheal females, collect a urine sample from the subject and perform a urine 
pregnancy test.
7.
Perform a physical examination and record vital signs.
8.
Record the % BSA involved with psoriasis (excluding face and scalp) 
(See Section 13.3, Appendix 3).
9.
Evaluate pruritus.
10.
Evaluate IGA. 
11.
Obtain serum samples for routine blood chemistry, hematology, 1,25(OH)2D, 25(OH)D, 
and serum pharmacodynamic sampling. Prepare them according to the Central Laboratory 
manual. 
12.
For selected subjects enrolled in the PK analysis: Collect blood sample for PK assessment.
13.
Obtain urine sample for urinalysis.
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14.
Distribute the container for urine collection and provide instructions for 24-hour urine 
collection, as necessary. Subject/subject’s parent/legal guardian can start collecting urine as 
of the screening visit day and subject’s parent will bring the container back to the site 
24 hours later. If the urine sample after fasting for 4 hours could not be performed on site, 
the subject’s parent/legal guardian will be given the necessary material to perform it at 
home, and the parent will be asked to bring it back afterwards.
Note: all Screening labs must be reviewed by the Investigator prior to the Baseline visit.
15.
Question the subject’s parent/legal guardian or the subject (according to subject’s maturity 
level) about the occurrence of Adverse Events.  Events occurring after the Informed 
Consent Form has been signed should be recorded as Adverse Events in the eCRF.
16.
Schedule an appointment for the Baseline Visit.
8.1.2
Baseline visit
1.
Confirm the subject continues to meet the inclusion/exclusion criteria.
2.
Document discussion with subject and parent/legal guardian(s) in regard to continued 
willingness to participate in the study.  
3.
Confirm laboratory results from screening meet study entry requirements.
4.
For post menarcheal females, collect a urine sample and perform a urine pregnancy test. 
5.
Ask the subject and parent/legal guardian whether there have been any changes to his/her 
concomitant therapies/procedures (added, removed, or changed) since the previous visit.  
Document all changes on the Drugs/Therapies form in the eCRF.
6.
Perform a physical examination and record vital signs.
7.
Question the subject’s parent / legal guardian or subject (according to subject’s maturity 
level) about the occurrence of AEs.  Non-persuasive open ended questions are to be asked, 
such as “Have you noticed any change in your health since last visit?”.
8.
Question the subject’s parent / legal guardian or subject (according to subject’s maturity 
level) specifically about symptoms of kidney stones e.g. obvious hematuria or pyuria, or 
vague abdominal or flank pain/ discomfort, or possible pain radiating to the groin area.
9.
Record the % BSA involved with psoriasis (excluding face and scalp) (See Section 13.3).
10.
For subjects in the PK group only, collect blood for serum pharmacodynamic assessment. 
Prepare the sample according to the Central Laboratory Manual.
11.
For selected subjects enrolled in the PK analysis: Collect blood sample for PK assessment.
12.
Evaluate IGA.
13.
Evaluate pruritus.
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14.
Assign the subject a study drug kit using the IRT system (Section 6.1) and provide the 
subject and parent/legal guardian with study medication as well as instructions for 
application and dosing calendar.  .
15.
Demonstrate to the subject’s parent / legal guardian how to apply the study medication and 
how to document application on dosing calendar.
16.
Ask the subject’s parent / legal guardian to bring back the study medication on the next 
visit whether used or unused and to bring back the completed dosing calendar.
17.
Provide Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin Cleanser or equivalents 
to the subject and parent/legal guardian.
18.
Schedule an appointment for the Interim visits (Weeks 4 and 12). ). For subject with PK 
assessments, the sampling should occur within 121 hour after the last product 
application., Therefore, remind the subject and parent/guardian that no applications should 
be performed at home just before the PK blood sampling (AM or PM application 
depending on scheduled appointment time). 
8.1.3
Interim visits (Weeks 4 and 12)
1.
Evaluate IGA.
2.
Evaluate pruritus. 
3.
Document discussion with subject and parent/legal guardian in regards to continued 
willingness to participate in the study.  
4.
Record the % BSA involved by psoriasis (excluding face and scalp) (See Section 13.3).
5.
Obtain laboratory samples according to the Central Laboratory Manual.
5.1.
Blood
5.1.a.
Weeks 4 and 12: Obtain serum samples for routine blood chemistry and 
hematology.  
5.1.b.
Weeks 4 and 12: Obtain samples for pharmacodynamics parameters (serum 
sample for all subjects) and PK assessment (plasma sample only for selected 
subjects included in the PK evaluation). Sample obtained within 121 hour after 
the last product application. Therefore, remind the subject and parent/guardian 
that no applications should be performed at home just before the PK blood 
sampling (AM or PM application depending on scheduled appointment time).
5.1.c.
Week 12: Obtain serum sample for 25(OH)D and 1, 25(OH)2D.
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5.2.
Urine
5.2.a.
Weeks 4 and 12: Obtain urine sample for urinalysis and for post menarcheal 
females, also perform a urine pregnancy test on the urine sample collected.
5.2.b.
Weeks 4 and 12:  Distribute container and provide instructions for 24-hour urine 
collection to be started 1 day prior to Week 12 and Week 26/ET visits, 
respectively.  The study site should contact the parent/legal guardian 48 hours 
prior to the visit to remind them to start the urine collection.
5.2.c.
Week 12: For PD urine, get the 24-hour urine collection from subject or collect 
fasting (4 hour) urine sample when 24-hour collection is not possible.
6.
Question the subject and parent/legal guardian about the occurrence of AEs.  
Non-persuasive open ended questions are to be asked, such as “Have you noticed any 
change in your health since last visit?” 
7.
Question the subject’s parent / legal guardian or subject (according to subject’s maturity 
level) specifically about symptoms of kidney stones e.g. obvious hematuria or pyuria, or 
vague abdominal or flank pain/ discomfort, or possible pain radiating to the groin area.
8.
Week 12 only: Perform physical examination and record vital signs
9.
Ask the subject and parent/legal guardian whether there have been any changes to his/her 
concomitant therapies/procedures (added, removed, or changed) since the previous visit.  
Document all changes on the Drugs/Therapies form in the eCRF. 
10.
Collect the study medication that was dispensed at the previous visit.
11.
Review medication compliance and review dosing calendar for completeness.
12.
Weeks 4 and12: Dispense study medication to the subject’s parent/legal guardian using the 
IRT system.
13.
Weeks 4 and12: Provide Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin 
Cleanser or equivalents to the subject’s parent/legal guardian.
14.
Ask the subject’s parent/legal guardian to return the study medication for the next visit 
even if used or unused.
15.
Schedule an appointment for the Week 26/Early Termination Visit and remind the subject 
and parent/guardian to bring the completed dosing calendar.
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8.1.4
Week 26 Visit / Early Termination visit
1.
Document discussion with subject and parent/legal guardian in regards to continued 
willingness to participate in the study.  
2.
For post menarcheal females, collect a urine sample and perform a urine pregnancy test. 
3.
Record the % BSA involved by psoriasis (excluding face and scalp) (See Section 13.3).
4.
Perform physical exam and record vital signs.
5.
Obtain serum samples for routine blood chemistry, hematology, 1, 25(OH)2D, 25(OH)D 
and serum pharmacodynamic sampling and urine samples for urinalysis.  Prepare them 
according to the Central Laboratory manual. 
5.1.
For PD urine, get the 24-hour urine collection from subject or collect fasting (4 hour) 
urine sample when 24-hour collection is not possible.
5.2.
Provide a new container and instructions for 24-hour urine collection to be started 
1 day prior to Week 30 Follow-up visit (for all subjects in the PK group and at the 
Investigator’s discretion for all other subjects, such as in the case where the PD urine 
assessment from week 26 would be abnormal).  The study site should contact the 
parent/legal guardian 48 hours prior to the visit to remind them to start the urine 
collection.
6.
For selected subjects enrolled in the PK analysis: Collect blood sample for PK assessment.
7.
Evaluate IGA.
8.
Evaluate pruritus. 
9.
Question the subject’s parent/legal guardian or subject (according to subject’s maturity 
level) about the occurrence of Adverse Events.   Non-persuasive open ended questions are 
to be asked, such as “Have you noticed any change in your health since last visit?”
10.
Question the subject’s parent / legal guardian or subject (according to subject’s maturity 
level) specifically about symptoms of kidney stones e.g. obvious hematuria or pyuria, or 
vague abdominal or flank pain/ discomfort, or possible pain radiating to the groin area.
11.
Ask the subject and parent/legal guardian whether there have been any changes to his/her 
concomitant therapies/procedures (added, removed, or changed) since the previous visit. 
Document all changes on the Drugs/Therapies form in the eCRF. 
12.
Check that the subject and/or parent/legal guardian has brought back all the study 
medication, even if unused, and check on compliance and review the dosing calendar.
13.
Provide Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin Cleanser or equivalents 
to the subject’s parent/legal guardian.
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8.1.5
Week 30 Follow-up visit
1.
For post menarcheal females, collect a urine sample and perform a urine pregnancy test. 
2.
Record the % BSA involved by psoriasis (excluding face and scalp) (See section 13.3, 
Appendix 3).
3.
Obtain serum samples for laboratory testing (full panel) for subjects in the PK group. For 
all other subjects, obtain serum samples for laboratory testing at the Investigator’s 
discretion (all subjects). Obtain urine for urinalysis (all subjects).
4.
Obtain serum samples for 1,25(OH)2D, 25(OH)D and serum PD parameters for subjects in 
the PK group. For all other subjects, obtain serum samples at the Investigator’s discretion. 
Prepare them according to the Central Laboratory manual. 
5.
Obtain 24-hour urine sample for PD urine for subjects in the PK group and send it to the 
central lab for analysis. For all other subjects, obtain 24-hour urine sample at the 
Investigator’s discretion and send it to the central lab for analysis.
6.
For selected subjects enrolled in the PK analysis: Collect blood sample for PK assessment.
7.
Evaluate IGA.
8.
Evaluate pruritus. 
9.
Question the subject’s parent/legal guardian or subject (according to subject’s maturity 
level) about the occurrence of Adverse Events. Non-persuasive open ended questions are to 
be asked, such as “Have you noticed any change in your health since last visit?”
10.
Question the subject’s parent / legal guardian or subject (according to subject’s maturity 
level) specifically about symptoms of kidney stones e.g. obvious hematuria or pyuria, or 
vague abdominal or flank pain/ discomfort, or possible pain radiating to the groin area.
11.
Ask the subject and parent/legal guardian whether there have been any changes to his/her 
concomitant therapies/procedures (added, removed, or changed) since the previous visit. 
Document all changes on the Drugs/Therapies form in the eCRF. 
12.
After collecting all data from the subject (including laboratory samples results), complete 
the Exit form of the eCRF.
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8.1.6
Unscheduled visits
When necessary and exceptionally, unscheduled visits could take place due to an advent event 
(AE) needing a specific treatment, AE leading to withdrawal from the study, laboratory result(s) 
that warrant further testing, or other reason. Please complete appropriate eCRF AE form if 
necessary. Assessments to be performed will be at the Investigator’s discretion according to the 
reason for the Unscheduled visit.
8.2
Subject instructions (other than study drug(s) administration)
Subjects should wait at least six hours after the study treatment application before swimming or 
bathing. 
The Cetaphil® Moisturizing Cream or equivalent (provided by the Sponsor) may be used during 
the study as needed on non- treated areas of the skin. A Cetaphil® Gentle Skin Cleanser or 
equivalent (provided by the Sponsor) may be used for cleansing.
Subjects will be permitted to use medicated shampoos that do not contain corticosteroids or 
vitamin D derivatives to treat scalp psoriasis.  Tar products can be used on the face and scalp 
areas.
No other topical treatments, other than the test materials, will be permitted on the treated areas. 
However, emollients and sunscreen on healthy skin areas are permitted during the course of the 
study.
Dietary instructions: subjects will be asked to maintain the same dietary habits, especially 
calcium intake as before the study.  Subjects should maintain adequate hydration. Detailed 
instructions will be provided to the subjects regarding appropriate hydration in the subject 
instructions document.
It is recommended that the subject use protective clothing and other measures/precautions to 
protect themselves from excessive sun exposure while participating in this study.  
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9
STATISTICAL METHODS PLANNED
9.1
Statistical and analytical plans
A Statistical Analysis Plan (SAP) will be developed as a separate document. The SAP will 
contain a more detailed and technical description of specific data conventions, calculations and 
of statistical procedures for executing the analyses that are specified in the sections of the clinical 
trial protocol below.  Any change to the primary objective of the study or to the statistical 
method of primary endpoint will require the protocol and the SAP to be amended prior to 
database lock. Changes to the planned analyses of other non-primary endpoints, as well as any 
additional and unplanned statistical analyses will be documented in the clinical study report, and 
in an amended SAP if these changes occur before database lock. Any further change to the 
planned analyses (such as, addition of post-hoc analyses) made to the finalized SAP will be 
documented in the clinical trial report.
9.1.1
Analysis Endpoints
9.1.1.1
Efficacy Endpoints
Percentage of subjects with an IGA Score of 0 (clear) or 1 (almost clear).
Change from Baseline in Pruritus  
Change from Baseline in % BSA 
9.1.1.2
Key Safety Endpoints

Laboratory: Serum albumin-adjusted calcium, urine calcium : creatinine ratio, phosphorus, 
and PTH.

Adverse Events
9.1.1.3
Pharmacokinetic Endpoint
Ct
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9.1.2
Populations analyzed, evaluability and limitation / evaluation of bias
Prior to the final database lock of the study, a data review will occur to assess the potential bias 
of any data issues for final statistical analyses; and to determine the final subject populations for 
statistical analyses. Decisions made from the data review will be documented and any changes to 
the SAP will be made before database can be locked.
The statistical analyses will be performed based on the safety population.  
9.1.2.1
Safety Population
The Safety Population is defined as all subjects who have applied the study drug at least once. 
9.1.3
Data presentation and graphics
In general, the categorical variables will be summarized by frequency and percentage for each 
response category (N, %).  The continuous variables will be summarized using means, medians, 
minimum, maximum, and standard deviations for the data collected at each visit  
9.1.4
Efficacy analysis methods
9.1.4.1
Handling of missing data 
No missing data handling will be performed. All data will be summarized as observed. 
9.1.4.2
Analyses of the efficacy endpoints
No formal inferential statistical analysis will be performed.  IGA will be summarized by each 
category and by shift changes over time.  
In addition, observed and changes from baseline of the IGA and Pruritus over time will be 
summarized as continuous variables.  
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9.1.5
Safety analysis methods
No inferential statistical analysis is planned for safety endpoints of the study. 
The laboratory parameters at scheduled visits and change from Screening at post-baseline visit(s) 
will be summarized descriptively by treatment and by visit.  A shift table for lab parameters at 
Screening versus Week 26/ET will be provided when appropriate.  
Only Treatment-emergent Adverse Events (TEAEs) will be summarized. A TEAE is defined as 
an AE with an onset date on or after the first application of the study drug.  
TEAEs will be tabulated in frequency tables by System Organ Class and Preferred Term based 
on the Medical Dictionary for Regulatory Activities (MedDRA).  Additional summary tables will 
be provided for TEAEs that are considered serious (SAEs), related to the study drug(s), and 
severe. TEAEs that are AESIs, as well as TEAEs leading to discontinuation will also be 
summarized. For a given TEAE, a subject will be counted once even if he/she has experienced 
multiple episodes of that particular TEAE. Subgroup summaries of TEAEs will be provided 
based on gender, age group, and race when appropriate.
Prior and concomitant therapies and procedures will be summarized. A prior therapy/procedure 
is one that ends at or before baseline; and a concomitant therapy/procedure is one starting after 
the baseline visit.
Extent of study drug exposure and compliance will also be summarized.
9.1.6
Pharmacokinetics analysis 
Ct will be submitted after logarithmic transformation (Ln), to paired comparisons of Baseline and 
each subsequent time point. Ninety percent confidence intervals of the pairwise differences will 
be calculated using the Student’s t statistic. The limits of the intervals will be back-transformed 
into exponential to obtain 90% confidence intervals of the ratios of geometric means between 
time points, on the original scale.
PK/PD relationships will be investigated by correlating Ct with appropriate PD parameters, using 
Spearman coefficient and graphical illustrations.
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9.1.7
Subject disposition and baseline demographics
Subjects in each analysis population, treated, discontinued and reasons for discontinuation will 
be summarized. 
Demographics and baseline characteristics will also be summarized. 
9.1.8
Subgroup analyses
Subgroup analyses for safety data will be performed by age group, gender, and race. Details will 
be provided in the SAP.
9.1.9
Interim analyses and data monitoring
No interim analysis is planned in the study. 
There will be an Independent Data Monitoring Committee (IDMC) to safeguard the interests of 
the study participants.  Details of the IDMC are described in Section 7.2.2.1.
Frequency and type of statistical analyses to be performed for IDMC review will be detailed in 
the IDMC Charter.  
9.2
Sample size determination
9.2.1
Assumptions  
No formal sample size calculation has been performed.
9.2.2
Sample size calculation
As a screen failure rate of approximately 40 percent is expected, screening of approximately 
167 subjects is planned in order to achieve the target of 100 subjects enrolled into the study.
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10
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE
10.1
Personnel training
Site initiation visits will be conducted for all Principal Investigators and Study Coordinators to 
review and discuss protocol, study procedures, eCRF completion and basic GCP Regulations and 
ICH Guidelines. Evaluation scales will also be reviewed by the Sponsor’s Medical Expert or a 
clinical expert at Investigator Training Meetings.  Laboratory collection and processing 
procedures and other study required procedures will also be discussed.
Prior to enrolling any participants, each site will have a site initiation visit conducted. All CRAs 
responsible for study monitoring will receive the appropriate study specific training. The training 
will focus on the treatment indication, protocol, monitoring guidelines, SOPs, and study specific 
logistics.
An Investigator Site File will be provided to each site.  
10.2
Clinical monitoring
The conduct of the clinical trial will be closely monitored by representatives of GALDERMA to 
verify adherence to the clinical trial protocol, ICH-GCP guidelines, and applicable SOPs.  
The Investigator will allow the CRO/Sponsor’s representatives, to have direct access to all 
clinical trial records, eCRFs, corresponding subject medical records, study drug(s) dispensing 
records, study drug storage area, clinical trial facilities, and any other documents considered 
source documentation.  
The Investigator also agrees to assist the representative if required.
10.3
Data management
All data management procedures will be detailed in a Data Management Plan (DMP).
The DMP will describe the Electronic Data Capture (EDC) system that will be used to collect 
data, and whether the data management activities are performed internally or outsourced.  
Computerized edit checks and review processes will be performed on an ongoing basis as 
outlined in the DMP until all data clarifications are resolved.  The data will be exported to be 
stored in SAS datasets.  After all data clarifications are resolved, coding is approved, and 
subject’s evaluability is determined, the database will be locked.
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10.4
Quality assurance / audit / inspection
The clinical trial is conducted under the sponsorship of GALDERMA in compliance with the 
applicable international and local regulatory requirements as well as applicable ICH guidelines 
and in accordance with the SOPs for clinical trial conduct and monitoring from GALDERMA 
and/or the Contract Research Organization (CRO).
Audits of clinical trial centers may be conducted by the Sponsor/CRO representatives, and 
inspection may be performed by Regulatory Authority inspectorates or IRBs/IECs before, 
during, or after the clinical trial.  
The Investigator will allow and assist the CRO/Sponsor’s representatives, IRBs/IECs and any 
regulatory agency to have direct access to all requested clinical trial-related records.
For the audits performed by, or on behalf of, GALDERMA auditors, acknowledgement letters(s) 
will be provided by Quality Assurance.
10.5
Changes in clinical trial conduct / amendments
10.5.1
Clinical trial conduct
With the exception of eliminating an immediate hazard to a subject, the Investigator should not 
deviate from the clinical trial protocol or implement any changes without written approval from 
the Sponsor and prior review and documented approval/favorable opinion from the IRB/IEC of a 
protocol amendment.
Changes that involve only logistical or administrative changes to the clinical trial protocol are 
authorized. The Investigator should document and explain any deviation from the clinical trial 
protocol.
10.5.2
Amendments
The Sponsor may modify the clinical trial protocol at any time for ethical, medical, or scientific 
reasons.
No amendment can be implemented at clinical trial centers, unless to eliminate an immediate 
hazard to the subjects, without having been submitted to FDA for its review and having obtained 
approval from the IRB with responsibility for review and approval of the clinical trial.
Once this amended protocol is implemented by each study center, it will apply to newly enrolled 
subjects at that site. Current subjects will continue to follow the original protocol through to 
completion.
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11
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS
11.1
Independent Ethics Committee (IEC) or Institutional Review Board (IRB)
This clinical trial protocol and all amendments will be reviewed and approved by the appropriate 
IECs/IRBs.
11.2
Ethical conduct of the clinical trial
This clinical trial will be conducted in accordance with the protocol, the HELSINKI declaration 
(1964) and subsequent amendments, and the ICH GCP, and in compliance with applicable 
regulatory requirements. 
The Health Insurance Portability and Accountability Act (HIPAA) will apply to the study centers 
within the U.S.A. and the Personal Information Protection and Electronic Documents Act 
(PIPEDA) will apply to the sites in Canada.
11.3
Subject information and consent
All subjects who participate in this clinical trial are required to be fully informed about the 
clinical trial in accordance with GCPs guidelines, federal regulations, HIPAA or PIPEDA 
(when applicable) and guidelines and in accordance with local requirements.  
The ICF and Assent Form, approved by an IRB/IEC, will be fully explained to the subject and/or 
their parent/legal guardian.  
Prior to enrollment into the clinical trial, the subject and the subject’s parent/legal representative 
will sign and date the consent form and assent form(s). The Investigator is responsible for 
maintaining each subject’s consent form(s) in the Investigator’s site file and providing each 
subject, or his/her parent legal representative, with a copy of the signed and dated consent 
form(s).
11.4
Contractual requirements
A 
contractual 
agreement 
will 
be 
signed 
between 
the 
CRO/Sponsor 
and 
each 
Investigator/Institution.  This document will contain supplementary information, including 
financial terms, confidentiality, the clinical trial schedule, third party responsibility, and 
publication rights.
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11.5
Data collection and archiving
11.5.1
Data collection
The Investigator must maintain all required records for all subjects. Data for this clinical trial 
will be recorded in the subject’s source documents and on the eCRFs provided by the Sponsor. 
All data should be recorded on the eCRFs completely and promptly.  
11.5.2
Source documentation
The Investigator must keep accurate separate records (other than the eCRFs) of all subject visits, 
being sure to include all pertinent clinical trial-related information. A statement should be made 
indicating that the subjects have been included in this clinical trial and have provided signed 
written Informed Consent and Assent, as appropriate.  All AEs must be thoroughly documented.
Results of any diagnostic tests conducted during the clinical trial should also be included in the 
source documentation.  
11.5.3
Archives
All pertinent data, samples, photographs, correspondence, and reports, the original or amended 
clinical trial protocol, and all other material relating to the clinical trial will be maintained 
securely in Sponsor/CRO/Investigator/Institution archives for the legally required duration for 
archiving.
The Investigator/Institution should maintain the essential clinical trial documents as specified in 
Section 8 of ICH-GCP, and according to the applicable regulatory requirements.
The Investigator/Institution should take measures to prevent accidental or premature destruction 
of these documents.
If the Principal Investigator retires, relocates, or withdraws from the responsibility of keeping the 
clinical trial records for any other reasons, custody must be transferred to a person who will 
accept the responsibility.  The Sponsor/CRO must be notified in writing of the name and address 
of the new custodian.
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11.6
Insurance
A certificate attesting Third Party coverage of CRO/Sponsor will be provided upon request.
11.7
Investigator and Administrative Structure 
Designation of a Coordinating Investigator (CI) will be done pursuant to the European Agency 
for the Evaluation of Medicinal Products (EMA) guidance on “Coordinator Investigator 
Signature of Clinical Study Reports”.
Please refer to the Investigator Site List and completed FDA Form 1572 for each participating 
site.
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12
LITERATURE REFERENCE LIST
Farber EM, Nall L. Childhood psoriasis. Cutis. 1999 Nov;64(5):309-14.
Gerritsen MJ, Van De Kerkhof PC, Langner A. Long-term safety of topical calcitriol 3 microg 
g(-1) ointment. Br J Dermatol. 2001; 144(Suppl 58):17-9.
Katz HI, Hien, NT, Prawer SE, et al. Superpotent topical steroid treatment of psoriasis vulgaris –
clinical efficacy and adrenal function. J Am Acad Dermatol. 1987; 16:804-11.
Lewkowicz D, Gottlieb AB. Pediatric psoriasis and psoriatic arthritis. Dermatol Ther.
2004;17(5):364-75. 
Nanda A, Al-Hasawi F, Alsaleh QA. A prospective survey of pediatric dermatology clinic 
patients in Kuwait: an analysis of 10,000 cases. Pediatr Dermatol. 1999 Jan-Feb;16(1):6-11.
Schwartz, et al. A simple estimate of glomerular filtration rate in children derived from body 
length and plasma creatinine. Pediatrics. 1976; 58(2): 259-263.
Shull B, Haughey D, Koup J, et al. A useful method for predicting creatinine clearance in 
children. Clin Chem. 1978; 24(7): 1167-1169.
Data on file: Evaluation of the efficacy and safety of twice daily application of calcitriol 3 mcg/g 
ointment and its vehicle, in the treatment of chronic plaque psoriasis. Galderma 
RD.06.SRE.18053
Data on file: Evaluation of the efficacy and safety of twice daily application of calcitriol 3 mcg/g 
ointment and its vehicle, in the treatment of chronic plaque psoriasis. Galderma 
RD.06.SRE.18054
From General Practice Notebook “Rules of Nines - Pediatric subjects”: 
http://www.gpnotebook.co.uk/simplepage.cfm?ID=-999620530&linkID=30283&cook=yes 
(accessed 30 March 2009).
Other References
ICH E3 Structure and Contents of Clinical Reports
ICH E6 Good Clinical Practice
ICH E8 General Considerations for Clinical Trials
Investigator’s Brochure 
The Declaration of Helsinki (1964) and latest updates
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13
APPENDICES
13.1
Appendix 1 Unauthorized Therapy
The list provides examples of treatments known to impact upon calcium homeostasis.  If the 
Investigator becomes aware of a drug used in a particular country that does not appear on the list 
below, this can be discussed with the Sponsor’s Medical Advisor on a case-by-case basis.  
The trade names used below are the ones most commonly encountered for the drugs listed; there 
may be some variability in trade names in different countries participating in the study, which is 
acceptable.  The investigator is expected to review all concomitant medications taken by the 
subjects.  Subjects enrolled in this study should not receive any treatment impacting on calcium 
homeostasis other than the drug, (calcitriol 3 mcg/g) ointment under investigation.
Drugs that may cause alterations in serum or urine calcium levels:
aminocaproic acid (trade names include Amicar, Cyklokapron)
amiodarone (trade names include Cordarone, Pacerone)
androgen hormones
(trade names include Halotestin, Metandren, Deca-Durabolin, 
Testosterone)
betacarotene (trade names include Lumitene, Max-Caro)
anti-seizure medications (trade names include Apo-Carbamazepine, Gabapentin, Klonopin, 
Keppra, Lamictal, Tegretol, Trileptal) 
chlorthalidone (trade names include Hygroton, Thalitone)
clopamide (trade names include Brinedine)
cyclosporine (trade names include Neoral, Sandimmune)
diltiazem (trade names include Cardizem, Cartia XT, Dilacor XR, Diltia XT, Tiazac)
glucocorticoids
(generic 
names 
include 
Betamethasone, 
Budesonide, 
Cortisone, 
Dexamethasone, 
Hydrocortisone, 
Methylprednisolone, 
Prednisolone, 
Prednisone, 
Triamcinolone).
lithium carbonate (trade names include Lithobid, Eskalith)
nifedipine (trade names include Adalat CC, Procardia, Procardia XL)
tamoxifene citrate (trade names include Nolvadex)
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tazarotene (trade names include Tazorac, Avage)
triamterene  (trade names include Dyrenium)
thiazide diuretics (trade names include Diucardin, Esidrix, Hydro-chlor, Microzide, Apo-Hydro, 
Urozide)
Vitamin D and Vitamin D analogs:
Alphacalcidol (trade names include One-Alpha)
calcipotriol (trade names include Dovonex)
calcitriol (trade names include Rocaltrol, Calcijex) 
dihydrotachysterol (trade names include DHT, Hytakerol)
Vit. D analogs approved for renal osteodystrophy including Hectoral and Paricalcitol 
(trade names include Zemplar)
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13.2
Appendix 2 Total Blood Sample Volumes and Number of Blood Sampling
18131
Standard analyses 
sampling volumes
Standard analyses 
sampling volumes (for 
subjects included in the 
PK assessment)
Total number of 
blood draws Per visit
Screening 
1, 25(OH)2D
25(OH)D
Pharmacodynamic serum
Routine hematology
Routine biochemistry 
PK blood sampling
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
---
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
5 mL
1
Baseline
Pharmacodynamic serum
PK blood sampling
---
---
5 mL
5 mL
1
Week 4
Pharmacodynamic serum
Routine hematology
Routine biochemistry 
PK blood sampling
5 mL
2 mL
3 mL
---
5 mL
2 mL
3 mL 
5 mL
1
Week 12
1, 25(OH)2D
25(OH)D
Pharmacodynamic serum
Routine hematology
Routine biochemistry
PK blood sampling
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
----
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
5 mL
1
Weeks 26/ET
1, 25(OH)2D
25(OH)D
Pharmacodynamic serum
Routine hematology
Routine biochemistry
PK blood sampling
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
---
2.5 mL
2.5 mL
5 mL
2 mL
3 mL 
5 mL
1
Week 30 Follow-up 1
1, 25(OH)2D
25(OH)D
Pharmacodynamic serum
Routine hematology
Routine biochemistry
PK blood sampling
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
---
2.5 mL
2.5 mL
5 mL
2 mL
3 mL
5 mL
1
Total  
70 mL
105 mL
6
Total volume of blood 
sampling
70 mL over 30+ weeks
105 mL over 30+ weeks
1 Laboratory testing (full panel) will be completed at Week 30 for subjects in the PK group. For all other subjects, laboratory testing 
at Week 30 will be completed at the Investigator’s discretion.
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13.3
Appendix 3 Calculation of Percent Body Surface Area Involved
Modified Rules of Nines (Pediatric subjects)*
The “Rules of Nines” are inaccurate due to the relative disproportion of body parts:

Hips and legs are smaller

Head, neck, and shoulders are larger
Hence, a pediatric subjects version is available in chart form that estimates burn area as it 
changes with age.  Alternatively, as estimate can be made from the following for a child up to 
the age of one (1) year:

Head and neck total for front and back:  18%

Thorax and abdomen - front:  18%

Thorax and abdomen - back:  18%

Each upper limb total for front and back:  9%

Each lower limb total for front and back:  14%
Over the age of one (1) year, the relative percentage of BSA changes:

The head decreases by 1% per year

The lower limbs increase by 0.5% per year
Hence, by the age of ten (10) years, the relative proportions assume the values for adult BSA:

Perineum becomes 1%

Each lower limb becomes a total of 18% front and back

Head and neck become 9% total for front and back.
*From 
General 
Practice 
Notebook 
“Rules 
of 
Nines 
-
Pediatric 
subjects”: 
http://www.gpnotebook.co.uk/simplepage.cfm?ID=-999620530&linkID=30283&cook=yes 
(accessed 30 March 2009).
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Subject’s palm can also be used to estimate BSA and should be considered as a 1% surface area.
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13.4
Appendix 4 Maximal daily dose and maximal application dose based on body 
weight.
Body weight
(kg)
Maximal daily dosea
(g)
Maximal dose per applicationb
(g)
11
5.5
2.75
12
6
3
13
6.5
3.25
14
7
3.5
15
7.5
3.75
16
8
4
17
8.5
4.25
18
9
4.5
19
9.5
4.75
20
10
5
21
10.5
5.25
22
11
5.5
23
11.5
5.75
24
12
6
25
12.5
6.25
26
13
6.5
27
13.5
6.75
28
14
7
29
14.5
7.25
30
15
7.5
31
15.5
7.75
32
16
8
33
16.5
8.25
34
17
8.5
35
17.5
8.75
36
18
9
37
18.5
9.25
38
19
9.5
39
19.5
9.75
40
20
10
41
20.5
10.25
42
21
10.5
43
21.5
10.75
44
22
11
45
22.5
11.25
46
23
11.5
47
23.5
11.75
48
24
12
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Body weight
(kg)
Maximal daily dosea
(g)
Maximal dose per applicationb
(g)
49
24.5
12.25
50
25
12.5
51
25.5
12.75
52
26
13
53
26.5
13.25
54
27
13.5
55
27.5
13.75
56
28
14
57
28
14
58
28
14
59
28
14
60
28
14
a)
Maximal daily dose of Calcitriol 3mcg/g ointment is  0.5g ointment per kg of body weight or 28 g, whichever is the lower.
b)
Maximal dose per application of calcitriol 3mcg/g ointment is 0.25 of ointment per kg of body weight of 14 g, whichever is the 
lower.
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13.5
Appendix 5 NIH pediatric blood volume for research guideline
NIH pediatric blood volume
Body weight (kg)
Maximum draw in 6 wks (7 mL/kg)
11
77
12
84
13
91
14
98
15
105
16
112
17
119
18
126
19
133
20
140
21
147
22
154
23
161
24
168
25
175
26
182
27
189
28
196
29
203
30
210
31
217
32
224
33
231
34
238
35
245
36
252
37
259
38
266
39
273
40
280
41
287
42
294
43
301
44
308
45
315
46
322
47
329
48
336
49
343
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NIH pediatric blood volume
Body weight (kg)
Maximum draw in 6 wks (7 mL/kg)
50
350
51
357
52
364
53
371
54
378
55
385
56
392
57
399
58
406
59
413
60
420
61
427
62
434
63
441
64
448
65
455
66
462
67
469
68
476
69
483
70
490
71
497
72
504
73
511
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SAP_001.pdf: 
A Multicenter Open Label Uncontrolled Study of the Long Term Safety and Efficacy of Calcitriol 3 mcg/g 
Ointment Applied Twice Daily for 26 Weeks in Pediatric Subjects (2 To 17 Years of Age) With Mild to 
Moderate Plaque Psoriasis
NCT Number: NCT02125279
Date: 27 May 2014


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A MULTICENTER OPEN LABEL UNCONTROLLED STUDY OF THE LONG TERM 
SAFETY AND EFFICACY OF CALCITRIOL 3 MCG/G OINTMENT APPLIED 
TWICE DAILY FOR 26 WEEKS IN PEDIATRIC SUBJECTS (2 TO 17 YEARS OF 
AGE) WITH MILD TO MODERATE PLAQUE PSORIASIS
STATISTICAL ANALYSIS PLAN
RD.06.SPR.18131
Version Final
27MAY2014
This document is electronically approved and signed by: Biometrics Manager
 
 
Name
Reason for Signing
Date
Head of Department
30-May-2014
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TABLE OF CONTENTS
1
STUDY OBJECTIVES.....................................................................................................................5
2
STUDY DESIGN...............................................................................................................................5
3
EFFICACY AND SAFETY ASSESSMENT ..................................................................................5
3.1
Efficacy Assessment.....................................................................................................................8
3.1.1
Efficacy Measurements ..........................................................................................................8
3.2
Safety Assessment ........................................................................................................................9
3.2.1
Adverse Events (AE)...............................................................................................................9
3.2.2
Laboratory Safety Tests .........................................................................................................9
3.2.3
Physical Examination and Vital Signs ................................................................................10
4
EFFICACY AND SAFETY VARIABLES ...................................................................................11
4.1
Efficacy Variables ......................................................................................................................11
4.2
Safety Variables..........................................................................................................................11
5
POPULATIONS ANALYZED.......................................................................................................11
5.1
Safety Population .......................................................................................................................11
6
SAMPLE SIZE CONSIDERATION.............................................................................................11
7
STATISTICAL METHODS AND DATA CONSIDERATIONS ...............................................11
7.1
Study Subjects ............................................................................................................................12
7.1.1
Disposition of Subjects..........................................................................................................12
7.1.2
Protocol Deviations...............................................................................................................12
7.2
Efficacy Analysis ........................................................................................................................12
7.2.1
Data Sets Analyzed ...............................................................................................................12
7.2.2
Demographic and Baseline Characteristics........................................................................12
7.2.3
Medical History, Previous and Concomitant Therapies/Procedures...............................13
7.2.4
Compliance............................................................................................................................13
7.2.5
Efficacy Analysis...................................................................................................................13
7.2.6
Statistical and Analytical Issues...........................................................................................14
7.3
Safety Analysis............................................................................................................................15
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7.3.1
Extent of Exposure................................................................................................................15
7.3.2
Adverse Events......................................................................................................................16
7.3.3
Laboratory Parameters........................................................................................................16
7.4
Vital Signs and Physical Exam .................................................................................................17
7.5
Analysis Visit Definition............................................................................................................17
8
CHANGES FROM THE PROTOCOL ANALYSIS PLAN........................................................19
9
TABLE SHELLS AND REPORTING OUTPUT (GENERAL FEATURES)...........................19
9.1
Demographic and Baseline Characteristics Tables.................................................................19
9.2
Efficacy Tables ...........................................................................................................................19
9.3
Safety Tables...............................................................................................................................20
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1
STUDY OBJECTIVES
The primary objective of this study is to evaluate the safety of up to 26 weeks of treatment with 
calcitriol 3 mcg/g ointment when used twice daily, without occlusion, to treat pediatric subjects 
(2 to 17 years of age) with mild to moderate plaque psoriasis.
Additional objective is to evaluate the long-term efficacy of up to 26 weeks of treatment with 
calcitriol 3 mcg/g ointment when used twice daily, without occlusion, to treat pediatric subjects 
(2 to 17 years of age) with mild to moderate plaque psoriasis.
2
STUDY DESIGN
This is an open-label, uncontrolled, multicenter long-term safety and efficacy study in pediatric 
subjects (age 2-17) with mild to moderate plaque psoriasis.
  
Approximately one hundred and forty (140) subjects will be enrolled into this study.
Qualified subjects will receive calcitriol 3 mcg/g ointment for a period of up to 26 weeks. The 
subject’s parent/legal guardian or the subject under the responsibility of the parent/legal guardian 
will apply a thin film of study drug as needed to cover all involved areas twice daily, without 
exceeding a maximum of 0.5 g/kg of body weight or 28 g daily (whichever is the lower).  If the 
subject experiences complete clearing of psoriasis per physician assessment (i.e. an IGA of 0), 
the subject should discontinue the study drug but continue to follow the visit schedule through 
the Week 26 visit.  Treatment with study drug should be resumed if the IGA score is 0 and 4.
Subjects will be evaluated at screening, baseline and Weeks 4, 8, 12, 20, 26/Early Termination, 
and Follow-up visit Week 30. 
3
EFFICACY AND SAFETY ASSESSMENT
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Table 1
Schedule of Assessments
Clinical Trial Assessments
Screening 
Period
Treatment Period10
Follow-up 
Period
Screening
(Day -14)11, 15
V1
Baseline 
(Week 0)
V2
Week 41
V3
Week 81
V4
Week 121
V5
Week 201
V6
Week 26 / 
ET1, 5
V7
Week 301
V8
Informed Consent / Assent Form /HIPAA/PIPEDA
X
Demographics
X
Medical History
X
Previous Therapies/Procedures8
X
Physical examination and Vital signs2
X
X
X
X
Inclusion/Exclusion Criteria
X
X3
Urine Pregnancy Test (post menarcheal)
X
X
X
X
X
X
X
X
Record % Body Surface Area involved
X
X
X
X
X
X
X
X
Routine Blood Chemistry and Hematology
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
Pharmacodynamic Serum9
X
X
X
X
X
X
X12
Pharmacodynamic Urine9
X
X14
X14
X12
25(OH)D & 1,25 (OH)2D
X
X
X
X12
IGA
X
X
X
X
X
X
X
X
Pruritus
X
X
X
X
X
X
X
X
Drug application
Twice a day from Baseline to V716
Study drug Dispensing (D) and Accountability (A)4
D
D/A
D/A
D/A
D/A
A
Adverse Event information collection 7, 13
X
X
X
X
X
X
X
X
Concomitant Therapies/Procedures8
X
X
X
X
X
X
X
X
Moisturizer and cleanser dispensed6
X
X
X
X
X
X
Exit Form5
X
1    Visit window of +/- 3 days.
2    Physical Examination to include: weight and review of systems: skin, cardiovascular, respiratory, abdomen, head and neck, musculoskeletal, neurological, lymph nodes and psychological. 
Height is to be evaluated at Screening visit only. Vital Signs to include: blood pressure, pulse rate
 
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3  Reconfirm that subject continues to meet inclusion/exclusion criteria.
4    Total amount of Study Drug applied to involved skin should not to exceed 0.5 g/kg of body weight or 28g per day (whichever is the lower). First application to be made under the supervision of the
investigator or designee. Record daily administration on dosing calendar. Dosing calendar to be checked at each visit after Baseline.
5  Or at any time in case of early termination.
6    The Cetaphil® Moisturizing Cream and Cetaphil® Gentle Skin Cleanser or equivalents will be provided by the Sponsor
7  Events occurring after the Informed Consent Form and Assent Form (when applicable) have been signed should be recorded as Adverse Events in the eCRF
8    Any therapy or medication other than study ointment will be noted on the Drugs/Therapies Form.  Subjects that require a wash-out period of a prohibited therapy for 2 weeks, should be screen 
failed and may re-screen 1 time after completion of the washout period.
9    PD Serum (non-fasting): calcium, phosphorus, albumin (in order to calculate the serum albumin-adjusted calcium) and PTH.
   PD Urine: Urine calcium and creatinine on 24-hour urine specimen, when feasible or fasting (4 hours) urine sample in order to calculate Urine calcium: creatinine ratio.  Subjects that are   
toilet-trained should be actively encouraged to complete 24-hour urine collection. A urine collection container/material will be given to the subject / subject’s parent/legal guardian with the instruction 
to start collecting urine as of this visit and to bring the container back after the 24-hour/4-hour collection.
10   Unscheduled visit: When necessary and exceptionally, because of either an AE needing a specific treatment, AE leading to withdrawal from the study, or other reason.  An ongoing dialogue 
between subject, parent/legal guardian and investigators focusing on all aspects of the trial is encouraged.   Any new information that arises in relation to the trial and that might affect the willingness 
of the subject and/or parent/legal guardian should be discussed.  This brief discussion should be documented during each study visit.
11 Subjects rolling over from SPR.18132 may omit  the Screening Visit and proceed directly to the Baseline Visit after receipt of all required SPR.18132 Week 8 lab results and confirmation that the 
subject meets all inclusion and no exclusion criteria.  Naïve subjects must complete the SPR.18131 Screening visit per Table.
12 Lab assessment should only be done at Week 30 visit if results were abnormal at the Week 26/ET visit.
13Any subjects with suspected kidney stones are to be referred to the subject’s PCP for treatment and the IDMC will be consulted on a case-by-case basis.
14The visitbefore: Distribute container and provide instructions for 24-hour urine collection to be started 1 day prior to Week 12 and Week 26/ET visits.  The study site should contact the parent/legal 
guardian 48 hours prior to the visit to remind them to start the urine collection.
15Subjects may re-screen one time with written approval from the Sponsor prior to re-entry into the study.
16 At Baseline, the study nurse show the subject’s parents how to apply the drug.
 
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3.1
Efficacy Assessment
3.1.1
Efficacy Measurements
IGA and Pruritus evaluations will be assessed at each visit on all treated areas.  
3.1.1.1
IGA (as evaluated on all treated areas by a Board Certified Dermatologist)
The IGA will be evaluated at each visit on a 0 to 4 point scale. The following definitions will be 
used to score IGA:
0
Clear
No signs of psoriasis except for residual hypopigmentation / 
hyperpigmentation
1
Almost Clear
Just perceptible erythema, no induration, and no scaling
2
Mild
Mild erythema, no induration, and mild or no scaling
3
Moderate
Moderate erythema, mild induration, and mild or no scaling
4
Severe
Severe erythema, moderate to severe induration, and scaling of any 
degree
3.1.1.2
Pruritus (as evaluated on all treated areas)
Pruritus will be evaluated at each visit and scored on a 0 to 4 point scale. The following 
definitions will be used to score Pruritus:
Pruritus: an itching sensation.
0
None
No-itching
1
Mild
Slight itching, not really bothersome
2
Moderate
Definite itching that is somewhat bothersome without loss of sleep
3
Severe
Intense itching that has caused pronounced discomfort, night rest 
interrupted
4
Very Severe
Very severe itching that has caused pronounced discomfort during 
the night and daily activities
3.1.1.3
Other Assessments:
Percent Body Surface Area (BSA) involved will be assessed using the methodology shown in 
Protocol, Section 13.3, Appendix 3 (Calculation of Percent Body Surface Area Involved).
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3.2
Safety Assessment
A safety assessment will be conducted for all subjects at the screening visit (from the Informed 
consent signature) and every subsequent visit.  The safety parameters are AEs, laboratory safety 
tests, physical examination, and vital signs.
3.2.1
Adverse Events (AE)
Adverse events (AEs) are to be monitored throughout the course of the clinical trial (from the 
subject signed the Informed Consent Form to the end of the subject’s participation).  All AEs are 
to be reported on the Adverse Event Form of the eCRF with complete information as required, 
including onset/end dates of AEs, severity of AEs, relationship to the study drug, serious AEs 
and AEs of special interested. 
3.2.2
Laboratory Safety Tests
The following laboratory safety tests will be performed according to the Schedule of 
Assessments. 
Hematology:
White blood cell (WBC) count with differential, red blood cell (RBC) count, hemoglobin (Hb), 
hematocrit (hct), mean cell volume (MCV), and platelet count (Plt)
Blood chemistry (non-fasting):
Total protein, alanine aminotransferase (ALT) (SGPT), aspartate aminotransferase (AST)
(SGOT), alkaline phosphatase (ALP), blood urea nitrogen, creatinine, and bilirubin (total and 
conjugated).
Urinalysis:
A semi-quantitative urinalysis will be performed.  The following parameters will be evaluated: 
glucose, ketones, blood, proteins, leukocytes, and nitrites. 
Pharmacodynamic parameters:
Serum (non-fasting): calcium, phosphorus, albumin (in order to calculate the serum albumin-
adjusted calcium), PTH
Urine: Calcium and creatinine (in order to calculate urine calcium:creatinine ratio) on 24-hour 
urine specimens, when feasible, or fasting (4 hours) urine samples
Other Assessments

1, 25(OH)2D

25(OH)D 
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Urine Pregnancy Test
Post menarcheal female subjects of childbearing potential will have a urine pregnancy test 
performed at all visits.  For pre-menstrual subjects who begin menses after the Screening visit, 
pregnancy tests will be performed according to the Schedule of Assessments for females of 
childbearing potential (Baseline, Week 4, Week 8, Week 12, Week 20, Week 26/ET, and 
Week 30).
3.2.3
Physical Examination and Vital Signs
3.2.3.1
Physical examination
The following body systems should be evaluated as “normal” or “abnormal” by the Investigator, 
at the visits per the Schedule of Assessments:
Skin
Cardiovascular system
Respiratory
Abdomen
Head and neck
Musculoskeletal system
Neurological function (mental status exam [level of consciousness, cognitive function], 
cranial nerve assessment, reflex testing, motor system assessment, sensory system 
assessment)
Lymph nodes
Psychological
Weight will be recorded every time a physical examination is performed and height will be 
evaluated at Screening Visit only.
The Investigator may choose to further investigate any other sign that he/she observes during the 
physical examination.
3.2.3.2
Vital signs
Systolic and diastolic blood pressures and pulse rate will be performed after 5 minutes rest in 
sitting position.  
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4
EFFICACY AND SAFETY VARIABLES
4.1
Efficacy Variables
Percentage of subjects with an IGA Score of 0 (clear) or 1 (almost clear).
Change from Baseline in Pruritus  
Change from Baseline in % BSA 
4.2
Safety Variables
Key Safety variables are as follows:
Key Laboratory Parameters:
-
Serum albumin-adjusted calcium
-
urine calcium : creatinine ratio, 
-
phosphorus, 
-
PTH.
Adverse Events
5
POPULATIONS ANALYZED
5.1
Safety Population
The Safety Population is defined as all subjects who have applied the study drug at least once. 
All statistical analyses will be performed based on the safety population.  
Prior to the final database lock of the study, a data review will occur to assess the potential bias 
of any data issues for final statistical analyses. Subjects with major/minor protocol deviations 
will be identified in the  data review meeting. No per protocol population will be defined.
6
SAMPLE SIZE CONSIDERATION
No formal sample size calculation has been performed. See Protocol Section 9.2 “Sample size 
determination”.
7
STATISTICAL METHODS AND DATA CONSIDERATIONS
SAS version 9.2 for windows will be used for all statistical analyses.
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In general, the categorical variables will be summarized by frequency and percentage for each 
response category (N, %).  The continuous variables will be summarized using means, medians, 
minimum, maximum, and standard deviations for the data collected at each visit.   
7.1
Study Subjects
Subject disposition, demographics, baseline characteristics, previous and concomitant therapies, 
previous and concomitant procedures, and subjects with major protocol deviations will be 
summarized for the safety population. 
7.1.1
Disposition of Subjects
The number of subjects and the number of subjects by site will be summarized in safety
population. 
The number and percentage of subjects who complete the study and subjects who discontinue 
from the study will be summarized as well as reasons for discontinuation. Discontinuation by site
and by visit will be tabulated. The discontinued subjects will be listed with the reason for 
discontinuation, along with the relevant comments recorded on the CRF exit form.
7.1.2
Protocol Deviations
According to protocol deviation plan, protocol deviations will be tracked by Chiltern Insight 
System and reviewed periodically during regular study team meetings and prior to IDMC 
meeting (at least every 4 months). In the data review meeting prior to database lock, protocol 
deviations will be reviewed and be categorized to major / minor protocol deviations. The 
decisions of major or minor deviations will be based on the eligibility criteria, study conduct 
and/or the impact to the efficacy and safety results.
The major/minor protocol deviation will be detailed in evaluability criteria document prepared 
before data review meeting.
7.2
Efficacy Analysis
7.2.1
Data Sets Analyzed
All efficacy variables will be analyzed based on the Safety population.
7.2.2
Demographic and Baseline Characteristics
Demographic and Baseline characteristics will be summarized for the Safety population. Age 
will be summarized as a continuous variable. Gender, race, skin phototype, and age group 
(2-5 years, 6-12 years, 13-17 years) will be analyzed as categorical variables. Baseline IGA, 
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baseline pruritus, baseline percent body surface area involved and Maximum allowed Daily dose 
will be summarized as continuous variables.
Subjects rolling over from previous studies SPR.18132 and SPR.18102 will be tabulated (if 
needed) and listed with previous treatment and subject ID information. 
7.2.3
Medical History, Previous and Concomitant Therapies/Procedures
Previous therapies are the therapies/medication with stop date at or prior to the first dose of study 
medication. Any therapy/medication usage post first dose of study medication are considered 
concomitant therapy.
Previous procedures are the procedures with stop date at or prior to the first dose of study 
medication. Any procedures post first dose of study medication are considered concomitant 
procedures.
Therapies/medication will be coded using WHODRUG dictionary (Version March 1, 2013). The 
number and percentage of subjects who take previous therapies and concomitant therapies will
be summarized by ATC class and WHO DRUG in the Safety population, respectively. 
Procedures will be coded using MedDRA dictionary (version 15.0). The number and percentage 
of subjects who take previous procedures and concomitant procedures will be summarized by 
System Organ Class and Preferred Term in the Safety population, respectively. 
Medical history will be provided in a subject-by-subject listing.
7.2.4
Compliance
Compliance will be based on actual study drug exposure and expected study drug exposure.
(Compliance = Actual study drug exposure /Expected study drug exposure). Compliance in days 
and compliance in doses are defined in Section 7.3.1.
7.2.5
Efficacy Analysis 
No formal inferential statistical analysis will be performed. All efficacy data will be summarized 
as observed based on analysis visit as well as additional analysis visit of Week 26 (LOCF, last 
observation carried forward). (Section 7.5). Analysis visit of Week 26 (LOCF) will be assigned 
as the last available data (excluding unscheduled visit) during treatment period. If there is no data 
available post baseline, the baseline visit will be used.
IGA and pruritus will be summarized over time by each category and by shift change. 
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Observed and changes from baseline of the IGA, Pruritus, and Percent BSA over time will be 
summarized as continuous variables. Additionally, change from baseline in efficacy data over 
time will be presented graphically. 
In addition, IGA, pruritus, and Percent BSA will be summarized descriptively by gender, race, 
and age group (2-5 years, 6-12 years, 13-17 years). 
7.2.6
Statistical and Analytical Issues
7.2.6.1
Adjustment for Covariates
Not applicable as there is no formal inferential statistical analysis will be performed.
7.2.6.2
Handling of Dropouts or Missing Data
All data will be summarized as observed based on analysis visit as well as additional analysis 
visit of Week 26 (LOCF, last observation carried forward) (Section 7.6). If there is missing 
baseline data, screening visit data will be used.
Week 26 (LOCF) will be assigned based on last available data during the treatment period, 
including baseline. 
7.2.6.3
Interim Analyses and Data Monitoring
No interim analysis is planned for this study.
7.2.6.4
Multicenter Studies
This is an open-label, uncontrolled, multicenter long-term safety and efficacy study. No center 
effect will be examined.
7.2.6.5
Multiple Comparison/Multiplicity
Not applicable.
7.2.6.6
Use of an Efficacy Subset of Patients
The Per-Protocol population (PP) is not planned for this study. Subjects who have protocol 
deviations will be identified during the data review meeting prior to database lock.
7.2.6.7
Active-Control Studies Intended to Show Equivalence
Not applicable.
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7.2.6.8
Examination of Subgroups
Descriptive summaries of IGA, pruritus, and percent BSA will be performed by gender, race, 
and age group (2-5 years, 6-12 years, 13-17 years). 
7.3
Safety Analysis
7.3.1
Extent of Exposure
7.3.1.1
Study Duration
Study duration is calculated as the date of the last visit including follow up period minus the date 
of the baseline visit plus one. Study duration will be summarized by descriptive statistics. 
7.3.1.2
Treatment Duration
Treatment duration is calculated as the date of the last application minus the date of the first 
application plus one. If the date of the last application is not available, the date of the last visit 
during treatment period will be used in calculation. If the date of the first application is not 
available, the baseline date will be used in calculation.  
7.3.1.3
Study Drug Exposure
The study drug is applied twice daily. Temporary drug discontinuations and dose modifications 
is permitted in instances of out-of-range laboratory results, local tolerability issues, and 
clearing/worsening of disease. Subjects also have missed doses due to other unexpected reasons. 
Reason for missed doses (either temporary drug discontinuations or dose modification),
incidence of temporary drug discontinuation and dose modification, and corresponding duration 
will be summarized and examined.
Actual study drug exposure and expected study drug exposure will be calculated in two 
definitions (in days and in doses). Missed doses due to complete clearing of psoriasis (IGA=0) 
will be excluded from the expected exposure. Any other missed dose due to non-safety or safety 
reason, even protocol allowed, will not be deducted from the expected study drug exposure.
Actual study drug exposure in days = Treatment duration (days) – number of days with no 
applications in both PM and AM (temporary drug discontinuations).
Actual study drug exposure in doses = Treatment duration *2 – number of missed doses.
Expected study drug exposure in days = Treatment duration (days) – number of days with no 
applications due to complete clearing of psoriasis (IGA=0) only.
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Expected study drug exposure in doses = Treatment duration * 2 – number of missed doses due 
to complete clearing of psoriasis (IGA=0) only.
Compliance will be based on actual study drug exposure versus expected study drug exposure. 
Compliance will be a good index of data integrity rather than protocol deviations 
Compliance (%) in days = Actual study drug exposure in days /expected study drug exposure in 
days.
Compliance (%) in doses = Actual study drug exposure in doses /expected study drug exposure 
in doses.
Actual study drug exposure, expected study drug exposure, and compliance in two definitions (in 
days or in doses) will be summarized.
7.3.2
Adverse Events
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA)
dictionary (version 15.0). 
Treatment-emergent adverse events (TEAEs) is defined as an AE with an onset date on or after 
the first application of the study drug. TEAEs will be tabulated in frequency tables by System 
Organ Class and Preferred Term for whole study and by period (Day 1 to Day 90, Day 91 to End 
of Treatment, Follow-up period). Additional summary tables will be provided for TEAEs that are 
considered serious (SAEs), related to the study drug(s), severe, and possibly related to Calcium 
Metabolism from predefined SOCs/HLGT . TEAEs of special interested and TEAEs leading to 
discontinuation will also be summarized. For a given TEAE, a subject will be counted once even 
if he/she has experienced multiple episodes of that particular TEAE. Subgroup summaries of 
TEAEs will be provided based on gender, race, and age group (2-5 years, 6-12 years, 
13-17 years) when appropriate.
7.3.3
Laboratory Parameters
Analysis visit will be applied for the laboratory parameter summaries. 
Descriptive statistics for each laboratory parameter will be provided for scheduled visit and for 
the changes from Screening at each post-baseline visit. “Final” visit (Week 26 (Final)) will be 
defined as the last post-baseline available observation during the treatment period.
A shift table for the laboratory data at Screening versus Final will be constructed for laboratory 
parameters for which numeric reference ranges are available.  The number of subjects below,
within, and above the laboratory reference ranges at Screening versus Final will be summarized. 
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For each laboratory test, a complete data listing will be provided for subjects who have any 
laboratory results outside the reference ranges, and for subjects who have any laboratory results 
with clinical significance.
Plot of mean change from screening and spaghetti plot (all-subjects-in-one figure or selective
individual subject figure) will be used to explore the trend of laboratory data change over the 
study, especially for serum albumin-adjusted calcium, urine calcium/creatinine ratio, 
phosphorus, PTH. Box-and-Whisker plots for PTH and Calcium/Creatinine ratio by visit will be 
constructed for data exploration.  
7.4
Vital Signs and Physical Exam
Descriptive statistics for vital signs parameter will be provided for scheduled visit and for the 
changes from Baseline at Week 12 and Week 26. “Final” visit (Week 26 (Final)) will be defined
as the last post-baseline available observation during the treatment period. Nominal eCRF visit 
will be used as analysis visit.
Physical exam will be provided in a subject-by-subject listing.
7.5
Analysis Visit Definition
All efficacy variables, vital signs, and laboratory data will be summarized by analysis visit. 
Analysis visit will be assigned according to the following algorithm to summarize the efficacy 
data by proper visit window interval. Study day is calculated as visit date minus the date of first 
application plus 1. Visit during treatment period will be used for analysis visits of Baseline to 
Week 26 assignment. Week 30 Follow-up will be the post-treatment/follow-up visit.
If multiple measurements are taken in the same interval, the one closest to the target study day 
will be used for the analysis. If two measurements are taken with equal differences in timing 
compared with the target date, the nominal visit number (recorded on the CRF page) will used.
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Table 2
Analysis Visit for Efficacy Data Summaries
Analysis Visit
Analysis Visit 
Number in 
Derived Dataset
Target Study Day
Visit Window for IGA, Pruritus, % 
BSA(Study Day)
Screening
-1
-
[ < 1 ]  
Baseline
1
1
[ <= 1 ] 
Week 4
2
29
[ 2 – 42 ] 
Week 8
3
57
[ 43 – 70 ]
Week 12
4
85
[ 71 – 112 ]
Week 20
5
141
[ 113 – 161]
Week 26
6
183
[162- 196]]
Week 26(LOCF)
6.999
-
Last available data during treatment 
period, including Baseline.
Week 30 Follow-up
7
-
Last available data during Follow-up 
data.
For efficacy data, screening visit will be assigned to analysis visit of screening as recorded on 
CRF page. If multiple measurements of screening due to rescreening or other unexpected 
reasons, the screening visit closest to date of first application will be chosen. If there is missing 
measurement at Baseline, Screening data will be used to impute the missing baseline data, if 
necessary, i.e. Baseline will be the last available data prior to first application. Only scheduled 
visit will be assigned into appropriate analysis visit; unscheduled visit will not be assigned to 
analysis visit, therefore, not in the summary.
When assigning the analysis visits for vital signs, no visit window will be applied; Nominal
eCRF visit will be used as analysis visit for summaries.
When assigning the analysis visits for laboratory data, no visit window will be applied, however, 
the following rules will be applied:
1. If sample date/time is prior to date/time of first application, the data will be considered as 
screening visit. If multiple measurements of screening due to rescreening, retest or other 
unexpected reasons, the data closest to date of first application will be chosen.
2. Lab data from scheduled visit will be considered first when assigning analysis visit of 
each scheduled visit. If there is no data from scheduled visit available within the visit 
window, the last of those corresponding unscheduled visit will be considered for 
assignment of analysis visits.
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3. When assigning Final visit, the lab data from the last post-baseline scheduled visit during 
treatment period will be considered first. If the last scheduled visit during treatment 
period have missing lab data due to any reason and there are subsequent unscheduled lab 
data available, the last of those corresponding unscheduled lab data will be assigned as 
Final visit. Otherwise, the previous visit lab data will be considered in the same manner. 
8
CHANGES FROM THE PROTOCOL ANALYSIS PLAN
No change from protocol analysis plan.
9
TABLE SHELLS AND REPORTING OUTPUT (GENERAL FEATURES)
The tentative list of tables to be produced in the reporting of this study is shown below.  All 
eCRF data will also be available as subject listings and the eCRF data will be available in 
CDISC compliant data set. A separate document will be prepared for list of tables/figures/listing.
All summaries are based on Safety population.
9.1
Demographic and Baseline Characteristics Tables 
Summary of Subject Enrollment
Summary of Subject Enrollment by Site within Country/Region
Summary of Subject Disposition
Summary of Subject Disposition by Site within Country/Region
Summary of Subjects with Major Protocol Deviations
Summary of Subject Demographics and Baseline Characteristics
Summary of Previous Therapies
Summary of Concomitant Therapies
Summary of Previous Procedure / Non-Drug Therapy
Summary of Procedure / Non-Drug Therapy
Summary of Compliance
9.2
Efficacy Tables
Efficacy results will be summarized descriptively and graphically versus time for all subjects and 
by subgroup.
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Summary of IGA (including Percentage of Subjects with an IGA Score of 0 (Clear) or 1 (Almost 
Clear))
Summary of Pruritus (including Change from baseline in Pruritus)
Summary of Percent BSA (including Change from Baseline in %BSA)
Summary of IGA by Gender, Race, and Age Group
Summary of Pruritus by Gender, Race, and Age Group
Summary of Percent BSA by Gender, Race, and Age Group
9.3
Safety Tables 
Summary of Study Duration
Summary of Treatment Duration
Summary of Medication Exposure
Overall Adverse Events
Adverse Events by System Organ Class and Preferred Term
Adverse Events by Preferred TermAdverse Events by System Organ Class and Preferred Term
and by Maximum Severity
Adverse Events by System Organ Class and Preferred Term and by Period
Serious Adverse Events by System Organ Class and Preferred Term 
Listing of Serious Adverse Events
Adverse Events Leading to Discontinuation by System Organ Class and Preferred Term
Listing of Adverse Events Leading to Discontinuation
Adverse Events Possibly related to Calcium Metabolism by System Organ Class and Preferred 
Term
Listing of Adverse Events Possibly Related Calcium Metabolism
Adverse Events Related to Study Drug by System Organ Class and Preferred Term
Adverse Events Related to Study Drug by Preferred Term
Listing of Adverse Events Related to Study Drug
Severe Adverse Events by System Organ Class and Preferred Term
Listing of Severe Adverse Events
Adverse Events of Special Interest by System Organ Class and Preferred Term
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Listing of Adverse Events of Special Interest
Summary of Laboratory Data (Descriptive Statistics and graph)
Shift table of Laboratory Data 
Listing of subjects with Laboratory Data out of reference range (and individual subjects spaghetti
plots for key lab parameters)
Listing of subjects with Clinical Significant Laboratory Data
Listing of subjects with Positive Urine Pregnancy Test Results
Summary of Vital Signs
Overall Adverse Events by Gender, Race, and Age Group
Adverse Events by System Organ Class and Preferred Term by Gender, Race, and Age Group
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