ESTEEM 1: Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01194219
• Collaborator: (none)
• Enrollment: 844
• Arms: 3
• Actual Duration (Months): 74.4

Study Details

Study Description

Brief Summary

This study evaluated the effects of an called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study was to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study was able to test for efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Drug: Apremilast; Drug: Placebo; Drug: Topical treatments or phototherapy	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 844 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Plaque Psoriasis
• Actual Study Start Date: Sep 9, 2010
• Actual Primary Completion Date: Feb 23, 2012
• Actual Study Completion Date: Nov 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Apremilast Subjects initially randomized to apremilast 30 mg twice a day, and who demonstrate a PASI 75 response at Week 32 will be randomized (1 to 1) to either continue to receive apremilast 30 mg ) BID or to receive placebo (until effect is lost). At the time effect is lost, subjects will be treated with apremilast 30 mg twice a day for the duration of their participation in the study.	Drug: Apremilast; Other Names: CC-10004 Otezla ; Drug: Placebo; Identical matching placebo
Placebo Comparator: Placebo Subjects initially randomized to placebo, are assigned to apremilast 30 mg twice a day beginning at Week 16 for the duration of the subject's participation in the study.	Drug: Apremilast; Other Names: CC-10004 Otezla ; Drug: Placebo; Identical matching placebo
Active Comparator: Apremilast 30 mg Apremilast 30 mg by mouth (PO) twice a day (BID). Participants initially randomized to apremilast 30 mg BID, and who were able to demonstrate a Psoriasis Area Severity Index (PASI) -75 response at week 32 were randomized (1 to 1) to either apremilast 30 mg BID or oral placebo (until effect is lost). At relapse/loss of response to therapy prior to Week 52 (the time at which 75% improvement in PASI score compared to baseline was lost) or at Week 52, participants were re-treated with apremilast 30 mg BID for the duration of their participation in the study. Non-responders or partial responders (PASI response <75) received additional topical therapies or phototherapy beginning at Week 32.	Drug: Apremilast; Other Names: CC-10004 Otezla ; Drug: Placebo; Identical matching placebo; Drug: Topical treatments or phototherapy; At week 32, participants considered partial responders or non-responders had the option of adding topical therapies and/or phototherapy to their treatment regimen.; Other Names: Corticosteroid creams Light Therapy

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline [Baseline to Week 16]

   PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing.

Secondary Outcome Measures

1. Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With At Least 2 Points Reduction From Baseline [Baseline to Week 16]

   The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator factored in areas that have already been cleared (ie, have scores of 0) and did not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.

2. Percent Change From Baseline in Percent of Affected Body Surface Area (BSA) at Week 16 [Baseline and Week 16]

   BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA - baseline BSA) / baseline BSA (%).

3. Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16 [Baseline to Week 16]

   Psoriasis Area Severity Index (PASI) scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing. PASI score percent change from baseline was calculated as 100* (visit score - baseline score)/baseline score (%).

4. Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline [Baseline to Week 16]

   A participant was classified as having at least a 50% improvement in PASI score from baseline, which was equivalent to a percent change from baseline ranging from -100% to -50%. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination.

5. Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16 [Baseline and Week 16]

   The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Participant's Assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value - baseline value.

6. Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 [Baseline to Week 16]

   DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being "A lot," "A little," or "Not at all" (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.

7. Change From Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16 [Baseline to Week 16]

   The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value.

8. Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline [Baseline to Week 16]

   PASI-75 response was the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. See Outcome Measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See OCM #2 for further description.

9. Kaplan Meier Estimate of Time to Loss of PASI-75 Response (Loss of Effect) at Week 32 During the Re-Randomized Treatment Withdrawal Phase [Week 32 to Week 52]

   Time to loss was the time between the re-randomization date and the date of the first assessment where loss of PASI-75 was observed (event); or the time between the re-randomization date and the date of the last PASI assessment in the Weeks 32-52 interval prior to addition of protocol-prohibited medication/therapy, or resumption of APR 30 BID, or discontinuation, or Week 52 if no loss (censored).

10. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase [Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.]

    An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.

11. Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 [Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks]

    The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure Period. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.

12. Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase [Weeks 0 to Week 16]

    Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].

13. Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260 [Week 0 to Week 260]

    Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females, ≥ 18 years of age at the time of signing the informed consent document

2. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

1. Have moderate to severe plaque psoriasis at Screening and Baseline

1. Must meet all laboratory criteria

2. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication

3. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication.

Exclusion Criteria:

1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.

.

1. Pregnant or breast feeding

2. History of allergy to any component of the study drug

3. Hepatitis B surface antigen positive at Screening

4. Anti-hepatitis C antibody positive at Screening

5. Active tuberculosis (TB) or a history of incompletely treated TB

6. Clinically significant abnormality on 12-Lead Electrocardiogram (ECG) at Screening

7. Clinically significant abnormal chest x-ray

8. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency

9. Active substance abuse or a history of substance abuse within 6 months prior to Screening

10. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening

11. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years)

12. Psoriasis flare or rebound within 4 weeks prior to Screening

13. Evidence of skin conditions that would interfere with clinical assessments

14. Topical therapy within 2 weeks of randomization

15. Systemic therapy for psoriasis within 4 weeks prior to randomization

16. Use of phototherapy within 4 weeks prior to randomization (ie, Ultraviolet B (UVB), psoralen and ultraviolet A (PUVA)

17. Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization

18. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization

19. Use of any investigational drug within 4 weeks prior to randomization

20. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources

21. Prior treatment with apremilast

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01194219
• Other Study ID Numbers: CC-10004-PSOR-008
• First Posted: Sep 2, 2010
• Last Update Posted: Mar 15, 2022
• Last Verified: Apr 1, 2020

• Keywords provided by Amgen: Plaque Psoriasis
• Additional relevant MeSH terms: Psoriasis; Apremilast

Study Results

Participant Flow

Recruitment Details	The study was conducted at 76 study centers in 8 countries

Arm/Group Title	Apremilast	Placebo	Apremilast-Apremilast	Placebo-Apremilast	APR-APR-Re-randomized to PBO	APR-APR-Re-randomized to APR	APR-APR-APR + Optional Topicals/UVB	PBO-APR-APR + Optional Topicals/ UVB	Apremilast (Long-term Extension)	Placebo-Apremilast (Long-term Extension)
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)	Participants who were initially randomized to APR 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16) remained on APR 30 mg BID during the Maintenance Phase (Weeks 16-32).	Participants who were initially randomized to identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32)	Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders [ie, having a ≥ Psoriasis Area and Severity Index score of 75 (PASI-75) response] were re-randomized to PBO during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who retained their ≥PASI-75 response through the Randomized Withdrawal Phase remained on PBO until week 52. Those participants who lost their PASI-75 improvement achieved at week 32, were switched back to APR 30 mg BID at the time loss of effect was observed. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260, and received APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders (ie, having a ≥PASI-75 response) were re-randomized to APR 30 mg BID during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) and non-responders (ie, having a response of <PASI-50), remained on APR 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. Those participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to placebo BID during the 16-week Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to APR 30 mg BID and continued dosing with APR 30 mg BID during the Maintenance Phase (Weeks 16-32). At week 32, all participants continued to receive APR 30mg BID. Those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) or non-responders (ie, having a response of < PASI-50) were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these partial or non-responders received additional topical or phototherapy. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to APR 30 mg BID during the 16-week placebo-controlled phase (Weeks 0-16) continued receiving APR 30 mg BID through the Maintenance Phase (Weeks 16-32) and were re-randomized to APR 30 mg tablets or placebo tablets BID during the Randomized Withdrawal Phase; participants were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and received APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to identically matching placebo BID during the placebo-controlled phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32) and Randomized Withdrawal Phase were eligible to participate in the Long-term Extension phase from Weeks 52-260 and continued on apremilast 30 mg tablets BID for the remainder of their participation.
Period Title: Placebo-Controlled Phase Weeks 0-16
STARTED	562	282	0	0	0	0	0	0	0	0
Received Apremilast	560	282	0	0	0	0	0	0	0	0
COMPLETED	503	249	0	0	0	0	0	0	0	0
NOT COMPLETED	59	33	0	0	0	0	0	0	0	0
Period Title: Placebo-Controlled Phase Weeks 0-16
STARTED	0	0	494	245	0	0	0	0	0	0
Received Apremilast	0	0	493	244	0	0	0	0	0	0
COMPLETED	0	0	424	215	0	0	0	0	0	0
NOT COMPLETED	0	0	70	30	0	0	0	0	0	0
Period Title: Placebo-Controlled Phase Weeks 0-16
STARTED	0	0	0	0	77	77	245	208	0	0
Received Topical + Light Therapy	0	0	0	0	0	0	126	91	0	0
COMPLETED	0	0	0	0	73	73	184	163	0	0
NOT COMPLETED	0	0	0	0	4	4	61	45	0	0
Period Title: Placebo-Controlled Phase Weeks 0-16
STARTED	0	0	0	0	0	0	0	0	306	153
Received at Least 1 Dose of IP	0	0	0	0	0	0	0	0	304	153
COMPLETED	0	0	0	0	0	0	0	0	86	41
NOT COMPLETED	0	0	0	0	0	0	0	0	220	112

Baseline Characteristics

Arm/Group Title	Apremilast	Placebo	Total
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)	Total of all reporting groups
Overall Participants	562	282	844
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.8 (13.07)	46.5 (12.72)	46.0 (12.95)
Sex: Female, Male (Count of Participants)
Female	183 32.6%	88 31.2%	271 32.1%
Male	379 67.4%	194 68.8%	573 67.9%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	2 0.4%	5 1.8%	7 0.8%
Asian	28 5%	16 5.7%	44 5.2%
Black or African American	18 3.2%	10 3.5%	28 3.3%
Native Hawaiian or Other Pacific Islander	5 0.9%	1 0.4%	6 0.7%
White	507 90.2%	250 88.7%	757 89.7%
Other	2 0.4%	0 0%	2 0.2%
Duration of Plaque Psoriasis (years) [Number]
<10 years	150	85	235
10 to < 20 years	159	73	232
≥ 20 years	253	122	375
Missing	0	2	2

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline
Description	PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward (LOCF) imputation was used.

Arm/Group Title	Placebo/Apremilast	Placebo (PBO)
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Measure Participants	562	282
Number [percentage of participants]	33.1 5.9%	5.3 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	27.8
	Confidence Interval	(2-Sided) 95%; 23.1 to 32.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With At Least 2 Points Reduction From Baseline
Description	The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator factored in areas that have already been cleared (ie, have scores of 0) and did not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used.

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast 30mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the Placebo-controlled Phase (weeks 0-16)
Measure Participants	562	282
Number [percentage of participants]	21.7 3.9%	3.9 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	17.8
	Confidence Interval	(2-Sided) 95%; 13.7 to 21.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Percent of Affected Body Surface Area (BSA) at Week 16
Description	BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA - baseline BSA) / baseline BSA (%).
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Participants with a baseline value and at least 1 postbaseline value were included. Last observation carried forward imputation was used.

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching PBO tablets BID during the Placebo-controlled Phase (weeks 0-16)
Measure Participants	559	278
Least Squares Mean (Standard Error) [percent change]	-47.77 (1.634)	-6.99 (2.317)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-40.78
	Confidence Interval	(2-Sided) 95%; -46.34 to -35.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16
Description	Psoriasis Area Severity Index (PASI) scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing. PASI score percent change from baseline was calculated as 100* (visit score - baseline score)/baseline score (%).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used. Participants with a baseline value and at least 1 postbaseline value are included .

Arm/Group Title	Placebo/Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Measure Participants	559	278
Least Squares Mean (Standard Error) [percent change]	-52.1 (1.37)	-16.8 (1.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-35.3
	Confidence Interval	(2-Sided) 95%; -39.9 to -30.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline
Description	A participant was classified as having at least a 50% improvement in PASI score from baseline, which was equivalent to a percent change from baseline ranging from -100% to -50%. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used.

Arm/Group Title	Placebo/Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Measure Participants	562	282
Number [Percentage of Participants]	58.7 10.4%	17.0 6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	41.7
	Confidence Interval	(2-Sided) 95%; 35.7 to 47.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16
Description	The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Participant's Assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value - baseline value.
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used. Participants with a baseline value and at least 1 postbaseline value are included.

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching PBO tablets BID during the Placebo-controlled Phase (weeks 0-16)
Measure Participants	559	277
Least Squares Mean (Standard Error) [units on a scale]	-31.5 (1.30)	-7.3 (1.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Based on an analysis of variance model for the change from baseline at Week 16, with treatment group as a factor (an ANOVA model).
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-24.2
	Confidence Interval	(2-Sided) 95%; -28.7 to -19.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16
Description	DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No, scores 3 or 0 respectively), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being "A lot," "A little," or "Not at all" (scores 2, 1, or 0 respectively). The DLQI total score is derived by summing all item scores, which has a possible range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used. Participants with a baseline value and at least 1 postbaseline value are included

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching PBO tablets BID during the Placebo-controlled Phase (weeks 0-16)
Measure Participants	556	274
Least Squares Mean (Standard Error) [units on a scale]	-6.6 (0.27)	-2.1 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Mean
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -5.4 to -3.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on an analysis of covariance model for the change from baseline at Week 16, with treatment group as a factor, the baseline value, and the treatment by baseline interaction term as covariates.

8. Secondary Outcome

Title	Change From Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16
Description	The SF-36 was a 36-item general health status instrument and consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used. Participants with a baseline value and at least 1 postbaseline value are included.

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching PBO tablets BID during the Placebo-controlled Phase (weeks 0-16).
Measure Participants	556	273
Least Squares Mean (Standard Error) [units on a scale]	2.28 (0.371)	-0.81 (0.529)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.08
	Confidence Interval	(2-Sided) 95%; 1.81 to 4.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline
Description	PASI-75 response was the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. See Outcome Measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See OCM #2 for further description.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Last observation carried forward imputation was used.

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast (APR) 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching PBO tablets BID during the Placebo-controlled Phase (Weeks 0-16)
Measure Participants	562	282
Number [percentage of participants]	20.3 3.6%	3.5 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	16.7
	Confidence Interval	(2-Sided) 95%; 12.8 to 20.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Kaplan Meier Estimate of Time to Loss of PASI-75 Response (Loss of Effect) at Week 32 During the Re-Randomized Treatment Withdrawal Phase
Description	Time to loss was the time between the re-randomization date and the date of the first assessment where loss of PASI-75 was observed (event); or the time between the re-randomization date and the date of the last PASI assessment in the Weeks 32-52 interval prior to addition of protocol-prohibited medication/therapy, or resumption of APR 30 BID, or discontinuation, or Week 52 if no loss (censored).
Time Frame	Week 32 to Week 52

Outcome Measure Data

Analysis Population Description

Analysis population consisted of participants who were re-randomized to placebo or apremilast 30mg BID at Week 32.

Arm/Group Title	APR-APR-Re-randomized to APR	APR-APR -Re-randomized to PBO
Arm/Group Description	Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders (ie, having a ≥PASI-75 response) were re-randomized to APR 30 mg BID during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with APR 30 mg BID through the Maintenance Phase (weeks 16-32). At Week 32, those participants who were considered responders (ie, having a ≥PASI-75 response) were re-randomized to PBO during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who retained their ≥PASI-75 response through the Randomized Withdrawal Phase remained on PBO until Week 52. Those participants who lost their PASI-75 improvement achieved at Week 32, were switched back to APR 30 mg BID at the time loss of effect was observed.
Measure Participants	77	77
Median (95% Confidence Interval) [Weeks]	17.7	5.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo/Apremilast, Placebo (PBO)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.649
	Confidence Interval	(2-Sided) 95%; 1.768 to 3.969
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
Description	An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.
Time Frame	Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.

Outcome Measure Data

Analysis Population Description

Safety population consisted of all participants who were randomized and received at least one dose of Investigational Product (IP)

Arm/Group Title	Apremilast	Placebo
Arm/Group Description	Participants were initially randomized to apremilast 30 mg tablets BID during the Placebo-controlled Phase (weeks 0-16)	Participants were initially randomized to identically matching placebo tablets BID during the Placebo-controlled Phase (weeks 0-16)
Measure Participants	560	282
Any TEAE	388 69%	157 55.7%
Any Drug-Related TEAE	224 39.9%	58 20.6%
Any Severe TEAE	20 3.6%	9 3.2%
Any Serious TEAE	12 2.1%	8 2.8%
Any Serious Drug-Related TEAE	4 0.7%	0 0%
Any TEAE leading to Drug Interruption	37 6.6%	13 4.6%
Any TEAE leading to drug withdrawal	29 5.2%	9 3.2%
Any TEAE Leading to Death	1 0.2%	1 0.4%

12. Secondary Outcome

Title	Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260
Description	The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure Period. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.
Time Frame	Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks

Outcome Measure Data

Analysis Population Description

The apremilast subjects as treated population, which includes all participants who were randomized to (at Week 0) or treated with (at Week 16) apremilast 30 mg BID, and received at least one dose of apremilast after randomization or Week 16.

Arm/Group Title	Apremilast
Arm/Group Description	Participants initially randomized to placebo or apremilast 30 mg tablets BID during the 16-week placebo-controlled phase (Weeks 0-16) continued to receive apremilast 30 mg BID through the maintenance phase; during the randomized withdrawal phase (Weeks 32-52) participants continued to receive apremilast 30 mg BID or were again randomized to either apremilast 30 mg BID or placebo and were transitioned to apremilast 30 mg BID after loss of response or in the long-term extension phase from Weeks 52-260,
Measure Participants	804
Any At TEAE	675 120.1%
Any Drug-Related TEAE	372 66.2%
Any Severe TEAE	78 13.9%
Any Serious TEAE	74 13.2%
Any Serious Drug-Related TEAE	12 2.1%
Any TEAE Leading to Drug Interruption	107 19%
Any TEAE Leading to Drug withdrawal	98 17.4%
Any TEAE Leading to Death	3 0.5%

13. Secondary Outcome

Title	Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase
Description	Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].
Time Frame	Weeks 0 to Week 16

Outcome Measure Data

Analysis Population Description

Included all participants who were randomized and received at least one dose of Investigational Product (IP).

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16)	Participants were initially randomized to apremilast 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16)
Measure Participants	282	560
Participants with any psoriasis flare [1]	7 1.2%	6 2.1%
Participants with any psoriasis rebound [2]	1 0.2%	1 0.4%
PASI ≥ 125% of Baseline score after last dose [3]	3 0.5%	3 1.1%

14. Secondary Outcome

Title	Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260
Description	Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].
Time Frame	Week 0 to Week 260

Outcome Measure Data

Analysis Population Description

Safety population consisted of all participants who were randomized and received at least one dose of IP; apremilast participants as treated

Arm/Group Title	Apremilast
Arm/Group Description	Participants initially randomized to placebo or apremilast 30 mg tablets BID during the 16-week placebo-controlled phase (Weeks 0-16) continued to receive apremilast 30 mg BID through the maintenance phase; during the randomized withdrawal phase (Weeks 32-52) participants continued to receive apremilast 30 mg BID or were again randomized to either apremilast 30 mg BID or placebo and were transitioned to apremilast 30 mg BID after loss of response or in the long-term extension phase from Weeks 52-260
Measure Participants	804
Participants with any psoriasis flare [1]	35 6.2%
Participants with any psoriasis rebound [2]	12 2.1%
PASI ≥ 125% of Baseline score after last dose [3]	26 4.6%

Adverse Events

Time Frame	AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study
Adverse Event Reporting Description	During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Arm/Group Title	Placebo (Placebo-Controlled Phase) Weeks 0-16		Apremilast (Placebo-Controlled Phase) Weeks 0-16		APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52		Apremilast (Apremilast Exposure Period) Weeks 0-260
Arm/Group Description	Participants randomized and received identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16)		Participants randomized and received apremilast 30 mg tablets BID during the Placebo-Controlled Phase (Weeks 0-16)		Participants re-randomized and received placebo tablets BID at Week 32. Data from Week 32 up to Week 52 when participants received placebo treatment.		Participants who received apremilast 30 mg tablets BID, regardless of when the apremilast exposure started (at Week 0 or at week 16), up until Week 260. Adverse events associated with apremilast treatment up to Week 260 were included. AEs that started more than 28 days after Placebo treatment and prior to resuming apremilast were excluded for participants who were re-randomized to Placebo at Week 32.
All Cause Mortality
	Placebo (Placebo-Controlled Phase) Weeks 0-16		Apremilast (Placebo-Controlled Phase) Weeks 0-16		APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52		Apremilast (Apremilast Exposure Period) Weeks 0-260
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo (Placebo-Controlled Phase) Weeks 0-16		Apremilast (Placebo-Controlled Phase) Weeks 0-16		APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52		Apremilast (Apremilast Exposure Period) Weeks 0-260
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/282 (2.8%)		12/560 (2.1%)		2/77 (2.6%)		74/804 (9.2%)
Blood and lymphatic system disorders
Microcytic anaemia	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Cardiac disorders
Acute myocardial infarction	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		4/804 (0.5%)
Angina unstable	0/282 (0%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Atrial fibrillation	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Cardiac arrest	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Cardiac failure	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		2/804 (0.2%)
Cardiac failure congestive	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Coronary artery disease	0/282 (0%)		0/560 (0%)		0/77 (0%)		6/804 (0.7%)
Mitral valve stenosis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Myocardial infarction	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Supraventricular tachycardia	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Endocrine disorders
Goitre	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Eye disorders
Retinal detachment	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Gastrointestinal disorders
Abdominal pain	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Diverticular perforation	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Inguinal hernia	1/282 (0.4%)		1/560 (0.2%)		0/77 (0%)		2/804 (0.2%)
Intestinal obstruction	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Leukoplakia oesophageal	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Small intestinal obstruction	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Umbilical hernia	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
General disorders
Adverse drug reaction	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Non-cardiac chest pain	0/282 (0%)		0/560 (0%)		1/77 (1.3%)		2/804 (0.2%)
Pyrexia	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Hepatobiliary disorders
Cholecystitis	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Cholecystitis acute	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Infections and infestations
Appendicitis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Bacterial infection	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Brain abscess	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Clostridium difficile colitis	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Diverticulitis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Influenza	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Meningitis viral	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Nasopharyngitis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Pneumonia	1/282 (0.4%)		1/560 (0.2%)		0/77 (0%)		2/804 (0.2%)
Pyelonephritis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Sepsis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Urinary tract infection	0/282 (0%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Injury, poisoning and procedural complications
Chemical burns of eye	0/282 (0%)		0/560 (0%)		1/77 (1.3%)		1/804 (0.1%)
Concussion	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Coronary artery restenosis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Incisional hernia	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Joint dislocation	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Ligament rupture	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Multiple injuries	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Post procedural haemorrhage	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Rib fracture	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Road traffic accident	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Tendon rupture	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Investigations
Blood bilirubin increased	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Heart rate increased	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Oxygen saturation decreased	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Metabolism and nutrition disorders
Hypokalaemia	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Obesity	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Musculoskeletal chest pain	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Osteoarthritis	0/282 (0%)		0/560 (0%)		0/77 (0%)		3/804 (0.4%)
Periarthritis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Rotator cuff syndrome	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Spinal column stenosis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Anal cancer	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Benign neoplasm of thyroid gland	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Breast cancer	0/282 (0%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Conjunctival primary acquired melanosis	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Malignant melanoma	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Pituitary tumour benign	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Prostate cancer	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Rectal cancer	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Renal cell carcinoma	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Squamous cell carcinoma of skin	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Thyroid cancer	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Nervous system disorders
Cerebrovascular accident	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Convulsion	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Haemorrhagic stroke	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Presyncope	0/282 (0%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Syncope	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Transient ischaemic attack	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		2/804 (0.2%)
Psychiatric disorders
Bipolar disorder	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Completed suicide	1/282 (0.4%)		0/560 (0%)		0/77 (0%)		0/804 (0%)
Depression	0/282 (0%)		0/560 (0%)		0/77 (0%)		2/804 (0.2%)
Renal and urinary disorders
Nephrolithiasis	0/282 (0%)		0/560 (0%)		0/77 (0%)		4/804 (0.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Vaginal haemorrhage	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		2/804 (0.2%)
Skin and subcutaneous tissue disorders
Ingrowing nail	0/282 (0%)		0/560 (0%)		0/77 (0%)		1/804 (0.1%)
Urticaria	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Vascular disorders
Orthostatic hypotension	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Peripheral arterial occlusive disease	0/282 (0%)		1/560 (0.2%)		0/77 (0%)		1/804 (0.1%)
Other (Not Including Serious) Adverse Events
	Placebo (Placebo-Controlled Phase) Weeks 0-16		Apremilast (Placebo-Controlled Phase) Weeks 0-16		APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52		Apremilast (Apremilast Exposure Period) Weeks 0-260
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/282 (31.9%)		260/560 (46.4%)		10/77 (13%)		503/804 (62.6%)
Gastrointestinal disorders
Diarrhoea	20/282 (7.1%)		105/560 (18.8%)		0/77 (0%)		163/804 (20.3%)
Nausea	19/282 (6.7%)		88/560 (15.7%)		0/77 (0%)		130/804 (16.2%)
Infections and infestations
Gastroenteritis	6/282 (2.1%)		10/560 (1.8%)		0/77 (0%)		41/804 (5.1%)
Nasopharyngitis	23/282 (8.2%)		41/560 (7.3%)		3/77 (3.9%)		131/804 (16.3%)
Sinusitis	5/282 (1.8%)		16/560 (2.9%)		1/77 (1.3%)		45/804 (5.6%)
Upper respiratory tract infection	21/282 (7.4%)		57/560 (10.2%)		2/77 (2.6%)		183/804 (22.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/282 (1.8%)		9/560 (1.6%)		2/77 (2.6%)		51/804 (6.3%)
Back pain	2/282 (0.7%)		14/560 (2.5%)		1/77 (1.3%)		50/804 (6.2%)
Nervous system disorders
Headache	13/282 (4.6%)		31/560 (5.5%)		0/77 (0%)		62/804 (7.7%)
Tension headache	12/282 (4.3%)		41/560 (7.3%)		2/77 (2.6%)		84/804 (10.4%)
Vascular disorders
Hypertension	7/282 (2.5%)		10/560 (1.8%)		0/77 (0%)		56/804 (7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 days. Investigator must delete confidential information before submission or defer publication to permit patent applications.