Conditions: Psoriasis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 50
Healthy volunteers: no

Brief summary:
Add-on Enstilar to Otezla therapy.

Detailed description:
50 adult patients with moderate to severe plaque psoriasis will be given OTEZLA® for 16 weeks with add-on Enstilar.

Arms:
arm 1: Otezla 30mg BID Enstilar QD

Interventions: intervention 1: Otezla
Intervention descriptions: intervention 1: Otezla 30mg BID

Protocol document:
Prot_SAP_000.pdf: 
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Clinical Study Protocol 
A Single Center Study to Evaluate the Effectiveness and Safety of add on 
Enstilar® in Patients Using OTEZLA® for Moderate to Severe Plaque 
Psoriasis 
 
Testing Facility  
Psoriasis Treatment Center of Central New Jersey 
59 One Mile Road 
East Windsor, NJ 08520 
(609) 443-4500 
 
Study Sponsor and Principal Investigator  
Jerry Bagel, MD 
 
 
Study Sub-Investigator(s) 
David Nieves, MD 
Brian Keegan, MD, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table of Contents 
 
PROTOCOL TITLE PAGE 
1 
SYNOPSIS ...........................................................................................................................…4 
2 
ETHICS AND REGULATORY OBLIGATIONS ...................................................................7 
2.1 
Institutional Review Board (IRB) .....................................................................................7 
2.2 
Ethical Conduct of the Study ............................................................................................7 
2.3 
Subject Information and Consent ......................................................................................7 
2.4 
Pre-study Documentation Requirements ...........................................................................7 
     3 INTRODUCTION ....................................................................................................................7 
3.1 
Overview of Psoriasis........................................................................................................7 
3.2 
Rationale for Treating Plaque Psoriasis with OTEZLA and Enstilar® ............................8 
4 
STUDY OBJECTIVE...............................................................................................................8 
    5 INVESTIGATIONAL PLAN...................................................................................................8 
5.1 
Overall Study Design and Plan .........................................................................................8 
5.2 
Study Population Criteria ..................................................................................................9 
5.2.1 
Inclusion Criteria ...........................................................................................................9 
5.2.2 
Exclusion Criteria ........................................................................................................10 
5.3 
Source of Subjects and Recruitment Methods ................................................................11 
5.4 
Subject Enrollment and Treatment Assignment..............................................................11 
5.5 
Study Treatment ..............................................................................................................11 
5.5.1 
Apremilast Treatment (OTEZLA®) ............................................................................11 
5.5.1.1 
Apremilast (OTEZLA®) Description ......................................................................11 
5.5.1.2 
OTEZLA® Warnings and Precautions  ...................................................................12 
5.5.1.3 
OTEZLA® Dosing Schedule ...................................................................................14 
5.5.1.4 
OTEZLA® Dispensing and Dosage Record ............................................................14 
5.5.1.5 
OTEZLA® Dosage Adjustments .............................................................................14 
5.5.2 
Enstilar® ......................................................................................................................14 
5.5.2.1 
Enstilar® Description ..............................................................................................14 
5.5.2.2 
Enstilar® Dosing Schedule ......................................................................................14 
5.5.2.3 
Enstilar® Dispensing Record ...................................................................................14 
5.5.2.4 
Enstilar® Dosing Adjustments  ...............................................................................15 
5.5.3 
Permitted Concomitant Therapy ..............................................................................15 


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5.6 
  Study Procedures and Assessments ...............................................................................15 
5.6.1 
Informed Consent ........................................................................................................15 
5.6.2 
Inclusion and Exclusion Criteria .................................................................................16 
5.6.3 
Demographics and Medical History ............................................................................16 
5.6.4 
Urine Pregnancy Test ..................................................................................................16 
5.6.5 
Physical Examination ...................................................................................................17 
5.6.6 
Physician’s Global Assessment ...................................................................................17 
5.6.7 
Psoriasis Area Severity Index  .....................................................................................17 
5.6.8 
Body Surface Area .......................................................................................................17 
5.6.9 
Patient Reported Outcomes .........................................................................................17 
5.6.10 
Early Discontinuation Procedures ...............................................................................18 
6.   ADVERSE EVENTS ...........................................................................................................18 
7    INVESTIGATIONAL PRODUCT HANDLING ................................................................22 
7.1          Investiational Product receipt .....................................................................................22 
7.2 
Investigational Product Storage ...................................................................................22 
8    RECORD RETENTION  .....................................................................................................23 
8.1 
Study Monitoring .........................................................................................................24 
8.2 
Statistics  ......................................................................................................................24 
8.2.1 
Additional Statistical Considerations ..........................................................................24 
8.3 
Schedule of Events ......................................................................................................25 
10    REFERENCES ...................................................................................................................26 
11    APPENDICES ...................................................................................................................27 
 
 
 
 
 


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PROTOCOL SYNOPSIS: 
OTEZLA® IN COMBINATION WITH ADD-ON ENSTILAR®  
Study Title 
A Single Center Study to Evaluate the Effectiveness and 
Safety of add on Enstilar® in Patients using OTEZLA® for 
Moderate to Severe Plaque Psoriasis 
Sponsors 
Jerry Bagel, MD 
Study Objectives 
Primary Objective: To determine if adding Enstilar® topical 
therapy can help OTEZLA® partial responders to achieve 
PASI 75 by week 12. 
Secondary Objective:  To evaluate the efficacy of 
combining OTEZLA® and Enstilar®  
To evaluate the safety of combining OTEZLA® and Enstilar® 
To evaluate the subject quality of life when combining 
OTEZLA® and Enstilar®  
Study Design 
50 adult patients with moderate to severe plaque psoriasis 
will be given OTEZLA® for 8 weeks.   
 
At week 8, patients who achieved between PASI 25-74 
response will receive 4 weeks of Enstilar® (calcipotriene and 
betamethasone dipropionate) Foam, 0.005%/0.064% in 
addition to continuing OTEZLA® therapy.  
 
Patients who do not meet PASI 25 at week 8 will be 
discontinued from the study. 
 
At week 12 (after 4 consecutive weeks of Enstilar® add on 
therapy), Enstilar® will be discontinued and these patients 
will continue Otezla® as monotherapy through week 16. 
 
Patients who achieve PASI 75 at week 8 will remain enrolled 
on Otezla® monotherapy through week 16. 
Study Centers 
Single Center 
Study Population 
Adult male and female subjects with moderate to severe 
chronic plaque psoriasis  
Main Inclusion 
Criteria 
Subjects must meet the following criteria to be enrolled in this 
study: 
1.Male or female adult ≥ 18 years of age;  
2. Diagnosis of chronic plaque-type psoriasis 
3. Moderate to severe plaque type psoriasis as 
defined at baseline by:  


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• PGA score of 3 or greater  
• BSA affected by plaque-type psoriasis of 10% or 
greater  
• PASI ≥ 12 
4. Able and willing to give written informed consent 
prior to performance of any study-related procedures 
     5. Must be in general good health (except for disease 
under study) as judged by the Investigator, based on 
medical history, physical examination, clinical 
laboratories, and urinalysis. (NOTE: The definition of 
good health means a subject does not have 
uncontrolled significant co-morbid conditions).   
Main Exclusion 
Criteria 
Subjects who meet any of the following criteria will be 
excluded from participation in this study: 
1. Other than psoriasis, any clinically significant (as 
determined by the investigator) cardiac, endocrinologic, 
pulmonary, neurologic, psychiatric, hepatic, renal, 
hematologic, immunologic disease, or other major disease 
that is uncontrolled. 
2. Forms of psoriasis other than chronic plaque-type (e.g., 
Pustular erythrodermic and/or guttate psoriasis) or drug 
induced psoriasis  
3.  Subjects who previously used any biologic agent for 
psoriasis.  
4.  Use of oral systemic medications for the treatment of 
psoriasis within 4 weeks (includes, but not limited to, oral 
corticosteroids, methotrexate, acitretin and cyclosporine).  
5.  Patient used topical therapies to treat psoriasis on the 
hands and/or feet within 2 weeks of the Baseline Visit 
(includes, but not limited to, topical corticosteroids, vitamin D 
analogs, or retinoids).  
6. Patient received UVB phototherapy within 2 weeks of 
Baseline. 
Study Drug 
Dosage and 
Administration 
All patients will receive OTEZLA® 30mg twice daily at week 
0 (baseline) through week 8.  At week 8, patients who 
achieved between PASI 25-74 response will receive 4 weeks 
of add-on Enstilar® (calcipotriene and betamethasone 
dipropionate) Foam, 0.005%/0.064% once daily in addition to 
continuing OTEZLA® 30mg twice daily.  
 
At week 12 (after 4 consecutive weeks of Enstilar® add on 
therapy), Enstilar® will be discontinued and patients will 
continue OTEZLA® 30mg twice daily as monotherapy 
through week 16. 


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Patients who achieve PASI 75 at week 8 will remain enrolled 
on OTEZLA® 30mg BID monotherapy through week 16. 
Study Endpoints 
 
Primary Endpoints: 
PASI 75 at week 12 for patients in the OTEZLA® + Enstilar® 
combination arm. 
 
Secondary Endpoints:  
PASI 25-74 at week 8. 
PASI, PGA, BSA, PGAxBSA and DLQI improvement at week 
8 
PASI, PGA, BSA, PGAxBSA and DLQI improvement at week 
12  
PASI PGA, BSA, PGAxBSA and DLQI improvement at week 
16 
Serious Adverse Events (SAE’s) 
Study Duration 
16 weeks 
The subject may continue to participate in this study until one 
of the following occurs: 
• Subject has not achieved PASI 25 at week 8 
• The subject experiences a significant or serious adverse 
event related to study drug; 
• Subjects who initially achieved PASI 75 at week 8 and lose 
response by week 12 may withdraw at their own request.  
• Subjects who received Enstilar® add-on therapy for 4 
weeks and have not achieved PASI 75 at week 12 may 
withdraw at their own request. 
• The subject is not willing to continue participation in the 
study; 
• Subject completes 16 weeks of study drug and evaluations 
• The Sponsor decides to terminate the study for any 
reason. 
 
 
 
 
 
 
 
 
 
 
 


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2        ETHICS AND REGULATORY OBLIGATIONS 
2.1 Institutional Review Board (IRB) 
Written IRB approval of this protocol must be obtained before the study is initiated.  
Compliance with Title 21 of the US Code of Federal Regulations (CFR), Part 56, is 
required in order to protect the rights and welfare of human subjects involved in this study.   
2.2 Ethical Conduct of the Study 
The study will be conducted in accordance with the ethical principles that have their 
origins in the Declaration of Helsinki and its amendments.  In addition, the study will be 
performed in compliance with Good Clinical Practices (GCP), including the archiving of 
essential documents. 
2.3 Subject Information and Consent 
The Informed Consent Form will be reviewed and approved by the IRB.  The purpose, 
duration and possible risks and benefits will be explained to each potential subject.  
Consent in writing must be obtained from the subject before enrollment into the study.  
Consents will be signed and dated as required by Title 21 of CFR, Part 50.  The consent 
will also comply with the requirements of the Health Insurance Portability and 
Accountability Act (HIPAA).  The original, signed Informed Consent Form will be retained 
by the Investigator.  A signed copy of the Informed Consent Form will be given to the 
subject.  Each subject will be assigned a subject number that will be used in lieu of the 
subject’s name on further research documentation. 
 
 
3 
INTRODUCTION 
3.1 
Overview of Psoriasis  
Psoriasis is a chronic immunological disease characterized by infiltration of the skin with 
activated T cells and by abnormal keratinocyte proliferation and differentiation, resulting 
in marked inflammation and thickening of the epidermis.  Psoriasis affects 1-3% of the 
world population, making it one of the most prevalent inflammatory immunological 
diseases.1 There are several clinical subtypes of psoriasis: plaque, guttate, 
erythrodermic, inverse, and pustular.  Plaque psoriasis is the most common type of 
 
 


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psoriasis affecting 75-80% of psoriasis sufferers.² It presents as raised silvery scale, 
which can cover large areas, with underlying erythema, itching, and discomfort. 
 
3.2  Rationale for Treating Plaque Psoriasis with OTEZLA® + Enstilar® 
OTEZLA® and Enstilar® are both effective in treating psoriasis.  The pivotal OTEZLA® 
Phase III trials (ESTEEM) determined that apremilast was effective in treating moderate 
to severe plaque psoriasis.  The primary endpoint at week 16 demonstrated significantly 
more apremilast-treated patients (33.1%) achieved the primary end point (PASI-75 at 
week 16) than did placebo patients (5.3%).3  Combination regimens that utilize a 
systemic agent with light therapy and/or a topical agent are becoming the standard of 
care in the United States4 and Europe5, confirming the observation of Lebwohl et al6 in 
2004, that the use of two or more therapies to treat patients with moderate to severe 
psoriasis seems to be the rule rather than the exception. Topical steroids play an in 
important role in the long term management of psoriasis and data from the COBRA trial 
suggests that super potent topical corticosteroids are appropriate and well tolerated for 
use when added to existing therapeutic regimens i.e. phototherapy, systemic and 
biologic therapy.7   A post hoc analysis of the Phase 3 ESTEEM 1 trial of apremilast was 
conducted to assess the efficacy and safety of apremilast with and without topical 
therapies and/or UVB phototherapy.  The analysis focused on the sub-group of patients 
who did not achieve PASI 75 at week 32.  At week 52, more patients receiving topical 
therapy and/or phototherapy achieved PASI 75 than did patients with apremilast alone.8  
This study is being conducted to determine if adding topical Enstilar® to Otezla® 
therapy can help patients who received a partial response at week 8 reach PASI 75 by 
week 12. 
 
4. STUDY OBJECTIVE 
To explore the effectiveness and safety of combining OTEZLA® and Enstilar® and to 
determine if add-on Enstilar® therapy can help partial responders at week 8 achieve 
PASI 75 at week 12.  
 
5. INVESTIGATIONAL PLAN 
5.1 Overall Study Design and Plan 
50 subjects affected with plaque psoriasis with body surface area greater than or equal 
to 10%, and physician’s global assessment greater than or equal to 3 and PASI greater 
than or equal to 12 will receive OTEZLA® 30 mg twice daily for 8 weeks. 
 
Patients who do not achieve at least a PASI 25 at week 8 will be discontinued from 
treatment and study procedures. 
 


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At week 8, subjects who have achieved a PASI 25-74 will receive Enstilar® 
(calcipotriene and betamethasone dipropionate) Foam, 0.005%/0.064% once daily for 4 
weeks in addition to continuing OTEZLA® BID.  These patients will then discontinue 
Enstilar® at week 12 and remain on OTEZLA® monotherapy through week 16. 
 
Patients who achieve PASI 75 at week 8 will remain enrolled in the study and continue 
OTEZLA® 30mg BID through week 16.  These subjects will not receive Enstilar® add-
on therapy.  
  
5.2 Study Population Criteria 
Males and females ≥ 18 years of age with moderate-to-severe chronic plaque psoriasis 
5.2.1 Inclusion Criteria 
Patients who meet all of the following criteria will be enrolled in the study: 
1.Male or female adult ≥ 18 years of age 
 
2. Diagnosis of chronic plaque-type psoriasis 
 
3. Moderate to severe plaque type psoriasis as defined at baseline by:  
• Physcian’s Global Assessment (PGA) score of 3 or greater  
• Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater  
• Psoriasis Area Severity Index of 12 or greater 
 
4. Able and willing to give written informed consent prior to performance of any 
study-related procedures 
5. Must be in general good health (except for disease under study) as judged by 
the Investigator, based on medical history, physical examination, clinical 
laboratories, and urinalysis. (NOTE: The definition of good health means a 
subject does not have uncontrolled significant co-morbid conditions).   
6. Females of childbearing potential (FCBP)† must have a negative pregnancy 
test at Screening and Baseline.  While on investigational product and for at least 
28 days after taking the last dose of investigational product, FCBP who engage 
in activity in which conception is possible must use one of the approved 
contraceptive§ options described below:  
Option 1:  Any one of the following highly effective methods:  hormonal 
contraception (oral, injection, implant, transdermal patch, vaginal ring); 
intrauterine device (IUD); tubal ligation; or partner’s vasectomy; 
OR 
Option 2:  Male or female condom (latex condom or nonlatex condom NOT made 
out of natural [animal] membrane [for example, polyurethane]; PLUS one 


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additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with 
spermicide; or (c) contraceptive sponge with spermicide. 
 
† A female of childbearing potential is a sexually mature female who 1) has not 
undergone a hysterectomy (the surgical removal of the uterus) or bilateral 
oophorectomy (the surgical removal of both ovaries) or 2) has not been 
postmenopausal for at least 24 consecutive months  (that is, has had menses at any 
time during the preceding 24 consecutive months). The female subject’s chosen form of 
contraception must be effective by the time the female subject is randomized into the 
study (for example, hormonal contraception should be initiated at least 28 days before 
randomization). 
 
5.2.2 Exclusion Criteria 
Patients will NOT be enrolled in this study if they meet any of the following criteria: 
1. Other than psoriasis, any clinically significant (as determined by the 
Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, 
hepatic, renal, hematologic, immunologic disease, or other major disease that 
is currently uncontrolled. 
2. Prior history of suicide attempt at any time in the subject’s life time prior to 
screening or randomization, or major psychiatric illness requiring 
hospitalization within the last 3 years. 
3. Pregnant or breast feeding, or considering becoming pregnant during the 
study.  
4. Active substance abuse or a history of substance abuse within 6 months prior 
to Screening. 
5. Malignancy or history of malignancy, except for: 
a. treated [ie, cured] basal cell or squamous cell carcinomas;  
b. treated [ie, cured] cervical intraepithelial neoplasia (CIN) or carcinoma in 
situ of cervix with no evidence of recurrence within the previous 5 years. 
6. Use of any investigational drug within 4 weeks prior to randomization, or within 
5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer). 
7. Prior treatment with apremilast. 
8. Forms of psoriasis other than chronic plaque-type (e.g., Pustular erythrodermic 
and/or guttate psoriasis) or drug induced psoriasis  
 
9. Subject has previously used any biologic agent for psoriasis. 
 


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10. Use of oral systemic medications for the treatment of psoriasis within 4 weeks 
(includes, but not limited to, oral corticosteroids, methotrexate, acitretin and 
cyclosporine).  
 
11.  Patient used topical therapies to treat psoriasis on the hands and/or feet 
within 2 weeks of the Baseline Visit (includes, but not limited to, topical 
corticosteroids, vitamin D analogs, or retinoids).  
 
12. Patient received UVB phototherapy within 2 weeks of Baseline. 
 
13. Patient has a known hypersensitivity to the excipients of OTEZLA® or Enstilar® 
as stated in the label.  
 
14. Any conditionwhich would place the subject at unacceptable risk if he/she were 
to participate in the study. 
 
5.3 
Source of Subjects and Recruitment Methods 
The Investigator will manage the recruitment of subjects upon approval of the study by 
the Institutional Review Board.  Subjects may be recruited from internal patient lists and 
outside IRB approved advertisements.   
5.4 
Subject Enrollment and Treatment Assignment 
50 subjects of either gender with moderate-to severe plaque psoriasis will randomized to 
receive OTEZLA® 30mg BID for 8 weeks.  Participation beyond week 8 will be 
determinate of subject response according to the study design.  
5.5 STUDY TREATMENT 
5.5.1 Apremilast Treatment (OTEZLA®) 
5.5.1.1 
Apremiliast (OTEZLA®) Description 
OTEZLA® is manufactured by Celgene Corporation.  The active ingredient in OTEZLA® 
tablets is apremilast.  Apremilast is a small-molecule inhibitor of phosphodiesterase 4 
(PDE4) specific for cyclic adenosine monophosphate (cAMP).  The chemical name of 
apremilast 
is 
acetamide, 
N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-
(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl].PDE4 inhibition results in 
increased intracellular cAMP levels.  The specific mechanism(s) by which apremilast 
exerts its therapeutic action in psoriasis patients is not well defined.  


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5.5.1.2 
OTEZLA® Warnings and Precautions 
 
Diarrhea, Nausea, and Vomiting  
There have been postmarketing reports of severe diarrhea, nausea, and vomiting associated with 
the use of OTEZLA. Most events occurred within the first few weeks of treatment. In some cases 
patients were hospitalized. Patients 65 years of age or older and patients taking medications that 
can lead to volume depletion or hypotension may be at a higher risk of complications from 
severe diarrhea, nausea, or vomiting. Monitor patients who are more susceptible to complications 
of diarrhea or vomiting. Patients who reduced dosage or discontinued OTEZLA generally 
improved quickly. Consider OTEZLA dose reduction or suspension if patients develop severe 
diarrhea, nausea, or vomiting.  
 
Depression  
Treatment with OTEZLA is associated with an increase in adverse reactions of depression. 
Before using OTEZLA in patients with a history of depression and/or suicidal thoughts or 
behavior prescribers should carefully weigh the risks and benefits of treatment with OTEZLA in 
such patients. Patients, their caregivers, and families should be advised of the need to be alert for 
the emergence or worsening of depression, suicidal thoughts or other mood changes, and if such 
changes occur to contact their healthcare provider. Prescribers should carefully evaluate the risks 
and benefits of continuing treatment with OTEZLA if such events occur. 
 
Psoriatic arthritis  
During the 0 to 16 week placebo-controlled period of the 3 controlled clinical trials, 1.0% 
(10/998) of subjects treated with OTEZLA reported depression or depressed mood compared to 
0.8% (4/495) treated with placebo. During the clinical trials, 0.3% (4/1441) of subjects treated 
with OTEZLA discontinued treatment due to depression or depressed mood compared with none 
in placebo treated subjects (0/495). Depression was reported as serious in 0.2% (3/1441) of 
subjects exposed to OTEZLA, compared to none in placebo-treated subjects (0/495). Instances of 
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OTEZLA, compared to none in placebo treated subjects (0/495). In the clinical trials, 2 subjects 
who received placebo committed suicide compared to none in OTEZLA-treated subjects.  
 
Psoriasis 
 During the 0 to 16 week placebo-controlled period of the 3 controlled clinical trials, 1.3% 
(12/920) of subjects treated with OTEZLA reported depression compared to 0.4% (2/506) treated 
with placebo. During the clinical trials, 0.1% (1/1308) of subjects treated with OTEZLA 
discontinued treatment due to depression compared with none in placebo-treated subjects 
(0/506). Depression was reported as serious in 0.1% (1/1308) of subjects exposed to OTEZLA, 
compared to none in placebo-treated subjects (0/506). Instances of suicidal behavior have been 
observed in 0.1% (1/1308) of subjects while receiving OTEZLA, compared to 0.2% (1/506) in 
placebotreated subjects. In the clinical trials, one subject treated with OTEZLA attempted suicide 
while one who received placebo committed suicide.  
 
Weight Decrease  
During the controlled period of the studies in psoriatic arthritis (PsA), weight decrease between 
5%-10% of body weight was reported in 10% (49/497) of subjects treated with OTEZLA 30 mg 
twice daily compared to 3.3% (16/495) treated with placebo [see Adverse Reactions (6.1)]. 
During the controlled period of the trials in psoriasis, weight decrease between 5%-10% of body 
weight occurred in 12% (96/784) of subjects treated with OTEZLA compared to 5% (19/382) 
treated with placebo. Weight decrease of ≥10% of body weight occurred in 2% (16/784) of 
subjects treated with OTEZLA 30 mg twice daily compared to 1% (3/382) subjects treated with 
placebo. Patients treated with OTEZLA should have their weight monitored regularly. If 
unexplained or clinically significant weight loss occurs, weight loss should be evaluated, and 
discontinuation of OTEZLA should be considered.  
 
Drug Interactions  
Co-administration of strong cytochrome P450 enzyme inducer, rifampin, resulted in a reduction 
of systemic exposure of apremilast, which may result in a loss of efficacy of OTEZLA. 
Therefore, the use of cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, 
carbamazepine, phenytoin) with OTEZLA is not recommended. . 


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5.5.1.3 
OTEZLA® Dosing Schedule 
OTEZLA® tablets will be supplied by Celgene Corporation and administered and taken 
approximately 12 hours apart without regard to meals. In order to minimize risks of 
gastrointestinal symptoms associated with initial therapy, all subjects will receive 
OTEZLA® for the first 5 days according to the titration schedule in the package insert. 
See Appendix A 
5.5.1.4 
OTEZLA® Dispensing and Dosing Record 
Subjects will return all unused OTEZLA® tablets to the study site.  Site personnel will 
keep a record of OTEZLA® dispensed to and returned by each subject and note any 
missed doses.   
 
5.5.1.5 
OTEZLA® Dosage Adjustments 
If an SAE or an adverse event that is thought to be related to OTEZLA® and is not 
alleviated by symptomatic intervention, OTEZLA® will be discontinued.   
 
Subjects who permanently discontinue OTEZLA® therapy under this protocol should 
receive standard care of psoriasis treatment as prescribed by their physician. 
 
5.5.2 ENSTILAR® (calcipotriene and betamethasone dipropionate) Foam, 
0.005%/0.064% 
 
5.5.2.1 
Enstilar® Description 
 
Enstilar® Foam is a combination of calcipotriene, a vitamin D analog, and 
betamethasone dipropionate, a corticosteroid, indicated for the topical treatment of 
plaque psoriasis in patients 18 years of age and older. Each gram of Enstilar® Foam 
contains 52.2 mcg calcipotriene hydrate (equivalent to 50 mcg of calcipotriene) and 
0.643 mg of betamethasone dipropionate (equivalent to 0.5 mg of betamethasone). 
 
5.5.2.2 
Enstilar® Dosing Schedule 
Enstilar® will be supplied by LEO Pharma A/S. and applied once daily for 4 weeks. 
5.5.2.3 Enstilar® Dispensing and Dosing Record 
Enstilar® will be dispensed to the study subjects by the authorized site personnel 
following instructions in Enstilar® Label. Subjects will return all unused Enstilar® to the 


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study site. Site personnel will keep a record of Enstilar® dispensed to and returned by 
each subject and missed doses will be recorded on a subject diary. See Appendix B 
5.5.2.4 Enstilar® Dosage Adjustments 
If an SAE or an adverse event that is thought to be related to Enstilar® and is not 
alleviated by symptomatic intervention, Enstilar® will be discontinued.  
5.5.3  Permitted Concomitant Therapy 
The use of steroid-free topical emollients is allowed during the study. Appropriate 
interventions (e.g., prescribed medications) may be performed as the investigator deems 
necessary to treat concomitant illnesses and/or safeguard the subjects’ wellbeing.  No 
investigational product or device may be used during the study.   
5.6  Study Procedures and Assessments 
This protocol will consist of a Screening Period (0-30 days), followed by an open-label 
treatment period of OTEZLA® for 8 weeks (Period A). At week 8 (Part B), subjects PASI 
scores will be evaluated and patients who achieve PASI 25-74 will be given add-on 
Enstilar® treatment for 4 weeks (through week 12) followed by OTEZLA® monotherapy 
through week 16.  
Subjects who do not achieve PASI 25 at week 8 will be discontinued from the study and 
follow standard of care from their provider.  
Subjects who achieve PASI 75 at week 8 will remain on OTEZLA® monotherapy and will 
not initiate treatment with Enstilar®.  
5.6.1 Informed Consent 
This Study will be conducted in compliance with CFR Title 21, Part 50 (Informed Consent 
of Human Subjects).  Informed consent will be obtained from each subject in writing 
before participation in the Study.  A signed copy of the Informed Consent Form will be 
provided to each subject.  A provision to obtain a signed authorization to provide protected 
health information to the study sponsor, internal quality assurance agencies, health 
insurance agencies, and other parties as specified in the Federal Health Insurance 
Portability and Accountability Act (HIPAA) privacy regulation will be included in the 
Informed Consent Document.  HIPAA authorization is voluntary.  However, since the use 
and release of health information is critical to the conduct of the study, subjects who do 
not provide authorization to use and disclose their health information will not be enrolled 
into the study.  Subjects who withdraw their authorization to use and release health 


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information during study participation will be formally discontinued from the study.  The 
investigator may use and release at any time all the information collected prior to a 
subject’s withdrawal of the authorization to all authorized parties to satisfy scientific, 
regulatory, and financial concerns. 
5.6.2 Inclusion and Exclusion Criteria 
Subjects’ eligibility to participate in the study will be determined according to the Inclusion 
and Exclusion Criteria during the screening period (0 – 30 days prior to the first dose of 
the study drug).  Subjects who ultimately do not satisfy the eligibility criteria except 
changing treatments and undergoing a washout period, will not be enrolled into the study.  
Subjects who need to meet eligibility requirements will be asked to make the necessary 
changes.  Subjects who agree and comply will be re-evaluated prior to Baseline.   
5.6.3 Demographics and Medical History 
The following information will be obtained for each subject during screening: date of birth, 
sex, race/ ethnic origin, medical and surgical history, including history of alcohol and drug 
abuse, year of diagnosis of plaque psoriasis, and current and previous anti-psoriasis 
treatments.  All current therapies for other medical conditions will be documented. Medical 
history will be reviewed and updated at the Baseline Visit to ensure that the patient 
remains eligible to participate in the study. 
5.6.4 Urine Pregnancy Test 
Pregnancy testing (urine β-human chorionic gonadotrophin [β-HCG]) will be conducted in 
all female subjects, except those without childbearing potential at Screening (-30 to -1) 
and Baseline Visits (Week 0) prior to the first dose of OTEZLA®, and then again at week 
16.  An interim urine pregnancy test may be performed if there is reason to believe the 
subject may have become pregnant during the study.  Subjects with a positive pregnancy 
test will not be eligible to participate or to continue to receive study treatment. 
 
A female of childbearing potential is a sexually mature female who 1) has not undergone 
a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical 
removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive 
months  (that is, has had menses at any time during the preceding 24 consecutive 
months). The female subject’s chosen form of contraception must be effective by the time 
the female subject is randomized into the study (for example, hormonal contraception 
should be initiated at least 28 days before randomization). 


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5.6.5 Physical Examination 
A physical examination, including vital signs measurements, will be performed according 
to the schedule of events.  Resting pulse and blood pressure (systolic and diastolic) 
measurements should be obtained in the sitting position with the subject resting for at 
least 5 minutes before measurements being taken. The physical examination should 
include a thorough evaluation of the subject's skin. Blood pressure and pulse should be 
measured before blood draws are performed.  Any clinically significant abnormalities 
discovered during physical examinations after the Screening / Baseline visit should be 
documented and evaluated as potential adverse events. 
5.6.6 Physician’s Global Assessment (PGA)  
PGA will be determined for all subjects throughout the study. PGA is a 6 point scale that 
records the overall disease severity at each clinical evaluation based on the average 
degree of erythema, induration, and scaling of areas affected by psoriasis.  PGA uses a 
scale of 0 = Clear, 1 = Minimal, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very Severe. 
See Appendix C 
 
5.6.7 Psoriasis Area Severity Index (PASI) 
PASI will be determined for all subjects throughout the study.  Four anatomical sites 
(head, trunk, upper and lower limbs) are assessed for erythema, thickness, and scaling 
on a scale of 0-4 and degree of skin surface area on a scale of 6.  The PASI is a validated 
instrument that has become standard in clinical trials for psoriasis. The sum of the scores 
are then totaled for the PASI score. Psoriasis Area Severity Index scores range from 0 to 
72, with higher scores reflecting greater disease severity.9 See Appendix D 
 
 
5.6.8  Body Surface Area (BSA) 
BSA will be determined for all subjects throughout the study. The subjects palm will be 
selected for the measuring unit of body surface area.  The physician will equate the 
number of palms affected by psoriasis to derive the BSA total. 
5.6.9  Patient Reported Outcomes 
Subjects will complete the PRO’s based on the schedule of assessments. Questionnaires 
should be prior to medical procedures and clinical evaluations.   
Dermatology Life Quality Index (DLQI)10 to assess symptoms and impacts of 
dermatologic diseases on quality of life.   See Appendix E 


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5.6.10  Early Discontinuation Procedures 
Subjects will be prematurely discontinued from the study under the following conditions: 
1. Subject does not reach PASI 25 or greater at week 8 
2. Subject requests to withdraw from the study. 
3. Subject is noncompliant with protocol schedule, restrictions, and/or 
requirements as deemed per investigator. 
4. Subject experiences an adverse event that makes it difficult or intolerable for 
the subject to continue treatment, or increases risk to the subject, or interferes 
with the investigator’s ability to clinically evaluate the progress of the subject’s 
treatment. 
5. Subject begins an unapproved concomitant therapy for psoriasis or another 
medical condition that may increase risk to the subject if continuing study 
treatment. 
6. Subject cannot be reached / lost to follow-up. 
7. The study investigator suspends or terminates the study. 
8. Other unanticipated reason. 
 
Any subject who prematurely discontinues the study should complete the week 16 (End 
of Study) assessments. Any subject who withdraws consent to participate in the study will 
be removed from further treatment and/or study observation immediately upon the date 
of request.  
6 
ADVERSE EVENTS 
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence 
occurring at any dose that may appear or worsen in a subject during the course of a 
study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or 
any concomitant impairment of the subject’s health, including laboratory test values (as 
specified by the criteria below), regardless of etiology. Any medical condition that was 
present prior to study treatment and that remains unchanged or improved should not be 
recorded as an AE. If there is a worsening of that medical condition this should be 
considered an AE. A diagnosis or syndrome should be recorded on the AE page of the 
Case Report Form rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
All AEs will be recorded by the Investigator(s) from the time of signing the informed 
consent through the end of the designated follow-up period. 
 


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Abnormal laboratory values defined as adverse events 
An abnormal laboratory value is considered to be an AE if the laboratory abnormality is 
characterized by any of the following: 
• Results in discontinuation from the study. 
• Requires treatment, modification/interruption of study drug dose, or any other 
therapeutic intervention. 
• Is judged by the Investigator(s) to be of significant clinical importance. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the 
diagnosis or syndrome should be recorded on the AE page of the CRF. If the 
abnormality was not a part of a diagnosis or syndrome, then the laboratory abnormality 
should be recorded as the AE. 
Serious adverse event 
A serious adverse event (SAE) is any AE which: 
• Results in death 
• Is life-threatening (i.e., in the opinion of the Investigator(s) the subject is at 
immediate risk of death from the AE) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity (a substantial 
disruption of the subject’s ability to conduct normal life functions) 
• Is a congenital anomaly/birth defect 
• Constitutes an important medical event 
Important medical events are defined as those occurrences that may not be 
immediately life threatening or result in death, hospitalization, or disability, but may 
jeopardize the subject or require medical or surgical intervention to prevent one of the 
other outcomes listed above.  Medical and scientific judgment should be exercised in 
deciding whether such an AE should be considered serious. 
Events not considered to be SAEs are hospitalizations which: were planned before 
entry into the clinical study; are for elective treatment of a condition unrelated to the 
studied indication or its treatment; occur on an emergency outpatient basis and do not 
result in admission (unless fulfilling other criteria above); are part of the normal 
treatment or monitoring of the studied indication and are not associated with any 
deterioration in condition. 
If an AE is considered serious, both the AE pages of the CRF and the SAE Report Form 
must be completed. 
For each SAE, the Investigator(s) will provide information on severity, start and stop 
dates, relationship to study drug, action taken regarding study drug, and outcome. 
 


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Classification of severity 
For both AEs and SAEs, the investigator(s) must assess the severity of the event. The 
AEs will be evaluated for severity according to the following scale: 
Grade 1 = Mild 
Grade 2 = Moderate 
Grade 3 = Severe 
Classification of Relationship/Causality of adverse events (SAE/AE) to study drug 
The Investigator(s) must determine the relationship between the administration of study 
drug and the occurrence of an AE/SAE as Not Suspected or Suspected as defined 
below: 
Not 
suspected: 
The temporal relationship of the adverse event to study 
drug administration makes a causal relationship 
unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient 
explanation for the observed event 
Suspected: 
The temporal relationship of the adverse event to study 
drug administration makes a causal relationship 
possible, and other medications, therapeutic 
interventions, or underlying conditions do not provide a 
sufficient explanation for the observed event. 
Immediate reporting of serious adverse events 
Any AE that meets the any criterion for a SAE requires the completion of an SAE Report 
Form in addition to being recorded on the AE pages of the CRF.  The Investigator(s) is 
required to ensure that the data on these forms is accurate and consistent.  This applies 
to all SAEs, regardless of relationship to study drug, that occur during the study, those 
made known to the Investigator(s) within 30 days after a subject’s last dose of study 
drug, and those made known to the investigator(s) at anytime that are suspected of 
being related to study drug. 
The SAE must be reported immediately (i.e., within 24 hours of the Investigators’ 
knowledge of the event) to Celgene Safety by facsimile.  A written report (prepared by 
the Investigator(s) using an SAE Report Form or a 3500A Medwatch form  is to be 
faxed to Safety (see below for contact information). 
Celgene Drug Safety Contact Information: 
Celgene Corporation      
Global Drug Safety and Risk Management    
86 Morris Ave.  
Summit, NJ  07901       
Fax:                 (908) 673-9115 


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E-mail:            drugsafety@celgene.com 
 
The SAE report should provide a detailed description of the SAE.  If a subject has died 
and an autopsy has been performed, copies of the autopsy report and death certificate 
are to be sent to Celgene as soon as these become available.  Any follow-up data will 
be detailed in a subsequent SAE Report Form or Medwatch form and sent to Celgene. 
The Investigator(s) is responsible for informing the Institutional Review Board/Ethics 
Committee (IRB/IEC) of the SAE and providing them with all relevant initial and follow-
up information about the event. The Investigator(s) must keep copies of all SAE 
information, including correspondence with Celgene and the IRB/IEC, on file.  All SAEs 
that have not resolved upon discontinuation of the subject’s participation in the study 
must be followed until either the event resolves completely, stabilizes/resolves with 
sequelae, or returns to baseline (if a baseline value is available). 
Pregnancies 
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless 
of age or disease state) of a female subject or the female partner of a male subject 
occurring while the subject is on study drug, or within 30 days of the subject’s last dose 
of study drug, are considered immediately reportable events.  Study drug is to be 
discontinued immediately and the subject instructed to return any unused portion of the 
study drug to the investigator(s).  The pregnancy, suspected pregnancy, or positive 
pregnancy test must be reported to Celgene Safety immediately facsimile using the 
Pregnancy Report form provided by Celgene. 
The female should be referred to an obstetrician-gynecologist experienced in 
reproductive toxicity for further evaluation and counseling. 
The Investigator(s) will follow the female subject until completion of the pregnancy, and 
must notify Celgene Safety of the outcome of the pregnancy as a follow-up on the follow 
up Pregnancy Reporting form. 
If the outcome of the pregnancy meets the criteria for immediate classification as a SAE 
(i.e., spontaneous or therapeutic abortion [any congenital anomaly detected in an 
aborted fetus is to be documented], stillbirth, neonatal death, or congenital anomaly 
[including that in an aborted fetus]), the Investigator(s) should follow the procedures for 
reporting SAEs (i.e., report the event to Celgene Safety by facsimile within 24 hours of 
the Investigator’s knowledge of the event). 
In the case of a live “normal” birth, Celgene Safety should be advised by facsimile within 
24 hours of the Investigator’s knowledge of the event. 
All neonatal deaths that occur within 30 days of birth should be reported, without regard 
to causality, as SAEs.  In addition, any infant death after 30 days that the Investigator(s) 
suspects is related to the in utero exposure to the study drug should also be reported to 
Celgene Safety by facsimile within 24 hours of the Investigators’ knowledge of the 
event. 


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If the female is found not to be pregnant, any determination regarding the subject’s 
continued participation in the study will be determined by the Investigator. 
Contraception Education 
The risks to a fetus or to a nursing child from apremilast are not known at this time.  
Results of the animal and in vitro studies can be found in the IB.    
All females of childbearing potential (FCBP) must use one of the approved 
contraceptive options as described in eligibility criteria while on investigational product 
and for at least 28 days after administration of the last dose of the investigational 
product. 
When a female subject of childbearing potential’s contraceptive measures or ability to 
become pregnant changes at the time of study entry or at any time during the study, the 
Investigator will educate the subject regarding options and correct and consistent use of 
effective contraceptive methods in order to successfully prevent pregnancy. 
 
Overdose 
 
Abuse, withdrawal, sensitivity, or toxicity to an investigational product should be 
reported as an AE. Overdose, accidental or intentional, whether or not it is associated 
with an AE should be reported as an AE.  Any sequela of an accidental or intentional 
overdose of an investigational product should be reported as an AE. 
 
If the sequela of an overdose is an SAE, then the sequela must be reported on 
an SAE report form. The overdose resulting in the SAE should be identified as the 
cause of the event on the SAE report form but should not be reported as an SAE itself. 
 
In the event of an overdose, the subject should be monitored as appropriate and should 
receive supportive measures as necessary. There is no known specific antidote for 
apremilast overdose. Actual treatment should depend on the severity of the clinical 
situation and the judgment and experience of the treating physician. 
 
Overdose for this protocol, on a per dose basis, is defined as ingestion of any more than 
the amount prescribed of apremilast (or matching placebo) tablets in any 24 hour period 
whether by accident or intentionally.  
 
 
7 INVESTIGATIONAL PRODUCT HANDLING 
 
7.1   Investigational Product Receipt 
At study initiation and as needed thereafter, OTEZLA® and Enstilar® will be shipped to a 
responsible person (e.g., a pharmacist) at the investigator's institution, who will check the 
amount and condition of the drug, and maintain a record of this information.   


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7.2   Investigational Product Storage 
Investigational product will be stored per the storage conditions identified on drug label.  
At the study site, all IP will be stored in a locked, safe area to prevent unauthorized 
access. 
Records of the actual storage conditions during the period of the study will be maintained. 
 
8 RECORD RETENTION 
The investigator must retain these documents according to local laws or requirements. 
Essential documents include, but are not limited to, the following: 
  
• Signed informed consent documents for all subjects;  
• Subject identification code list, screening log (if applicable), and enrollment log;  
• Record of all communications between the Investigator and the IRB/EC;  
Composition of the IRB/EC;  
• Record of all communications between the Investigator and Celgene. 
• List of Sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles 
in the study, curriculum vitae, and their signatures;  
• Copies of CRFs (if paper) and of documentation of corrections for all subjects;   
• IP accountability records;  
• All other source documents (subject records, hospital records, laboratory records, 
etc);  
• All other documents as listed in Section 8 of the ICH consolidated guideline on 
GCP (Essential Documents for the Conduct of a Clinical Trial). 
 
The Investigator must notify Celgene if he/she wishes to assign the essential 
documents to someone else, remove them to another location or is unable to retain 
them for a specified period.  The Investigator must obtain approval in writing from 
Celgene prior to destruction of any records.  If the Investigator is unable to meet this 
obligation, the Investigator must ask Celgene for permission to make alternative 
arrangements.  Details of these arrangements should be documented.  All study 
documents should be made available if required by relevant health authorities.  
Investigator/Institution should take measures to prevent accidental or premature 
destruction of these documents. 


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8.1 Study Monitoring  
The investigator will self-monitor all study records for accuracy, completeness, and 
compliance with the protocol and GCPs and federal regulations.  All study records will be 
made available to Celgene Corporation representatives upon request.  Study site facilities 
and study records will be made available to regulatory authorities’ inspectors if an 
inspection takes place.  The investigator will notify Celgene Corporation if this occurs.   
 
8.2  Statistics 
It is desired to enroll 50 patients based on the data from the Esteem trial which showed 
55% of subjects achieved between a PASI 25- PASI 74 response at week 8, hence it is 
expected that 30-40 patients will fit the continuation criteria at week 8 and be followed 
through week 16.   
The study will analyze data based on the non-responder imputation (NRI) method. This 
will be performed for each arm of the study (PASI 75 responders at week 8 and PASI 25-
74 responders at week 8. Subjects who do not complete week 16 assessments will be 
classsifed as non-responders.  
Since this is a pilot study with no formal hypothesis testing, statistical power/sample size 
is not formally presented in this protocol.  
 
Analysis will be performed by the Investigator on proportion of subjects achieving 
Psoriasis Area Severity Index (PASI) 75 response at week 12  
The investigator will also analyze PASI 25-74 at week 8, PASI, PGA, BSA, PGAxBSA 
and DLQI improvement at week 8, BSA, PGA and BSA x PGA and DLQI improvement at 
week 12.  PASI, BSA, PGA, BSA x PGA and DLQI at week 16.   This analysis will be 
done separately for both cohorts (PASI 75 responders at week 8 and PASI 25-74 
responders at week 8) using summary statistics. The Investigator will also analyze SAE’s 
by cohort. 
 
8.2.1 Additional Statistical Considerations 
Additional statistical procedures may be detailed in and performed according to a 
separate statistical plan at the discretion of sponsor-investigator. 
 
 
 
 
 


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8.3   Schedule of Events 
Procedure 
Screening 
BASELINE 
Week4 
Week 8 
Week 
12 
Week 
16 
Informed Consent 
X 
  
  
  
  
  
Demographics/Medical History 
X 
X 
  
  
  
  
Inclusion/Exclusion 
X 
X 
  
  
  
  
Physical Exam 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
Urine Preg Test 
X 
X 
  
  
  
X 
PASI 
X 
X 
X 
X 
X 
BSA 
X 
X 
X 
X 
X 
PGA 
X 
X 
X 
X 
X 
DLQI 
  
X 
  
X 
X 
X 
Vital Signs 
X 
X 
X 
X 
X 
IP dispensing/accountability 
  
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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REFERENCES 
 
1 Greaves MW, Weinstein GD.  Treatment of psoriasis.  New Engl J Med. 
1995;332(9):581-8. 
 
2 Camp RDR.  Psoriasis.  In:  Champion RH, Burton JL, Burbs DA, Breathnach SM, 
eds.  Textbook of Dermatology, 6th Edition.  1998;2:1589-1649. 
3.   Papp K, Reich, K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens 
RM, Day RM, Gordon KB, Korman NJ, Griffiths CE. Apremilast, an oral 
phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque 
psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial 
Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 
2015 Jul;73(1):37-49. doi: 10.1016/j.jaad.2015.03.049. 
4. Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM et al.  Guidelines of care 
for the management of psoriasis and psoriatic arthritis: Section 5. Guidelines of care for 
the treatment of psoriasis with phototherapy and photochemotherapy. J Am Acad 
Dermatol. 2010 Jan;62(1):114-35. 
 
5. Jensen P, Skov L, Zachariae C.  Systemic combination treatment for psoriasis:  A 
review.  Acta Derm Venereol. 2010; 90: 341-349. 
 
6. Lebwohl M, Menter A, Koo J, Feldman SR.  Combination therapy to treat moderate to 
severe psoriasis.  J Am Acad Dermatol. 2004; 50(3): 416-30. 
 
7. Koo JY. Relevance of the COBRA trial in current psoriasis practice. Cutis. 2007 
Nov;80(5 Suppl):4-11. 
 
8. Bagel J, Gold LS. Combining Topical Psoriasis Treatment to Enhance Systemic and 
Phototherapy: A review of the Literature. J Drugs Dermatol. 2017 Dec 1;16(12):1209-
1222. 
 
9. Frederiksson T, Pettersson U. Severe psoriasis: oral therapy with a new retinoid. 
Dermatologica. 1978;157:238-244. 
 
10. Finlay AY, Khan GK.  Dermatology Life Quality Index (DLQI).  April 1992.  Available 
from:  www.dermatology.org.uk. 
 
 
 
 
 


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7. APPENDICES 
 
Appendix A 
 
OTEZLA® dosing schedule 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 
6 
& 
thereafter 
AM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
AM/PM 
10MG 
10MG/10MG 10MG/20MG 20MG/20MG 20MG/30MG 30MG/30MG 
 
 
Appendix B 
Subject Diaries 
 
Storage 
●Keep study medication at room temperature. 
 ●Keep out of reach of children 
 
Enstilar Dosing 
●Apply once daily  
●Do not apply on face, underarms or groin  
●Avoid heat, flames or smoking when applying. 
●Do not bandage, cover, or wrap the treated area 
●Apply to affected areas and gently rub in. 
●Avoid bathing, showering or swimming right after applying the study medication.  
 
Dosing Diary 
●Record all doses on the diary as soon as possible.  
●Return diary and medication to all of your appointments. 
●Record any comments or information in “remarks” section for missed dose, 
adverse event, or change in medication. 
●Please make recordings clear and legible.  
 


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Appendix C 
Physician’s Global Assessment 
 
Physician’s Global Assessment (PGA) 
Score 
Grade 
Definition 
0 
Clear 
Plaque elevation = 0 (no elevation) 
Scaling = 0 (no scale) 
Erythema = 0 (residual post-inflammatory hyperpigmentation or 
hypopigmentation may be present) 
1 
Minimal 
Plaque elevation = ± (possible, but difficult to ascertain whether 
there is a slight elevation) 
Scaling = ± (surface dryness with some white coloration) 
Erythema = up to moderate (up to definite red color) 
2 
Mild 
Plaque elevation = slight (slight, but definite elevation, typically 
edges are indistinct or sloped) 
Scaling = fine (fine scale partially or mostly covering lesions 
Erythema = up to moderate (up to definite red coloration) 
3 
Moderate 
Plaque elevation = moderate (moderate elevation with rough or 
sloped edges) 
Scaling = coarser (course scale covering most of all of the lesions) 
Erythema = moderate (definite red coloration) 
4 
Severe 
Plaque elevation = marked (marked elevation typically with hard or 
sharp edges) 
Scaling = course (course, non-tenacious scale predominates) 
Erythema = severe (very bright red coloration) 
5 
Very Severe 
Plaque elevation = very marked (very marked elevation typically 
with hard sharp edges) 
Scaling = very coarse ( course, thick tenacious scale of over most of 
all of the lesions; rough surface) 
Erythema = very severe (extreme red coloration; dusky to deep red 
coloration) 
 
 
 
 
 
 
 
 
 
 
 


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Appendix D 
Psoriasis Area Index Severity 
 
 
 
 
 
 
 
 
 
 
 


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Appendix E 
Dermatology Life Quality Index 
 
DERMATOLOGY LIFE QUALITY INDEX 
 
 
 
 
 
 
 
 
 
 
 
 
 DLQI 
Hospital No:  
 
 
 
Date:  
 
 
 
 
 
Name:  
 
 
 
 
 
 
 
 
Score: 
Address: 
 
 
 
 
Diagnosis: 
 
 
 
 
 
 
The aim of this questionnaire is to measure how much your skin problem has 
affected your life OVER THE LAST WEEK.  Please tick  one box for each question. 
 
1. 
Over the last week, how itchy, sore,  
 
 
Very much 
 
 
painful or stinging has your skin    
 
 
A lot 
 
 
 
been?   
 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
2. 
Over the last week, how embarrassed 
 
 
Very much 
 
 
or self conscious have you been because  
A lot 
 
 
 
of your skin?  
  
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
 
3. 
Over the last week, how much has your   
 
Very much 
 
 
skin interfered with you going 
 
  
 
A lot 
 
 
 
shopping or looking after your home or   
 
A little  
 
 
garden?         
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
4. 
Over the last week, how much has your   
 
Very much 
 
 
skin influenced the clothes  
 
 
 
A lot 
 
 
 
you wear? 
 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
5. 
Over the last week, how much has your   
 
Very much 
 
 
skin affected any social or   
 
 
 
A lot 
 
 
 
leisure activities? 
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
6. 
Over the last week, how much has your   
 
Very much 
 
 
skin made it difficult for  
 
 
 
 
A lot 
 
 
 
you to do any sport? 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
7. 
Over the last week, has your skin prevented 
 
Yes 
 
 
 
you from working or studying? 
 
 
 
No 
 
 
Not 
relevant  
 
 
 
If "No", over the last week how much has   
 
A lot 
 
 
 
your skin been a problem at  
 
 
 
A little  
 


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Version 1 30 December 2017 
 
32 
 
 
work or studying?  
 
 
 
 
Not at all 
 
 
8. 
Over the last week, how much has your   
 
Very much 
 
 
skin created problems with your   
 
 
A lot 
 
 
 
partner or any of your close friends 
 
 
A little  
 
 
or relatives?   
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
9. 
Over the last week, how much has your   
 
Very much 
 
 
skin caused any sexual  
 
 
 
 
A lot 
 
 
 
difficulties?  
 
 
 
 
 
A little  
 
 
 
 
 
 
 
 
 
 
Not at all 
 
Not 
relevant  
 
10. 
Over the last week, how much of a  
 
 
Very much 
 
 
problem has the treatment for your 
 
 
A lot 
 
 
 
skin been, for example by making  
 
 
A little  
 
 
your home messy, or by taking up time?   
 
Not at all 
 
Not 
relevant  
Please check you have answered EVERY question. Thank you.  
©AY Finlay, GK Khan, April 1992 www.dermatology.org.uk, this must not be copied without the permission of the 
authors.