UNVEIL: A Phase 4 Study of Efficacy and Safety of Apremilast in Subjects With Moderate Plaque Psoriasis.

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02425826
• Collaborator: (none)
• Enrollment: 221
• Locations: 26
• Arms: 2
• Actual Duration (Months): 19.1
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will evaluate the clinical efficacy, the patients quality of life, and safety of oral apremilast 30 mg twice daily (BID) compared to placebo, in adult patients with moderate plaque psoriasis during the 16 week Placebo controlled Phase and then upto 1 year in the Extension Phase of the trial.

Condition or Disease	Intervention/Treatment	Phase
Parapsoriasis	Drug: Apremilast; Drug: Placebo; Drug: Placebo-Apremilast	Phase 4

Detailed Description

This is a Phase 4, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast in subjects with moderate plaque psoriasis. 221 participants were randomized 2 (apremilast):1 (placebo) at approximately 25 sites in the United States. Those randomized to the apremilast treatment group received apremilast 30 mg tablets orally twice daily for 52 weeks. Those randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally twice daily (BID) for 16 weeks. Beginning Week 16, those initially randomized to placebo were switched to receive apremilast 30 mg BID for an additional 36 weeks (52 weeks total).

Study enrolled adult patients with stable moderate plaque psoriasis, who are naïve to systemic psoriasis treatments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 221 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Multicenter, Randomized, Placebo-controlled, Double-blind, Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate Plaque Psoriasis
• Actual Study Start Date: Apr 20, 2015
• Actual Primary Completion Date: Feb 12, 2016
• Actual Study Completion Date: Nov 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apremilast Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.	Drug: Apremilast; Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.; Other Names: CC-10004, Otzela ; Drug: Placebo; Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.; Drug: Placebo-Apremilast; At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total); Other Names: Otezla CC-10004
Placebo Comparator: Placebo Placebo tablets BID during Weeks 0 to 16; at week 16, placebo participants were switched to apremilast 30 mg tablets BID for 36 weeks (from week 16 to week 52)	Drug: Placebo; Participants randomized to the placebo treatment group received placebo tablets (identical in appearance to the apremilast 30 mg tablets) orally BID for from weeks 0-16.; Drug: Placebo-Apremilast; At Week 16, those randomized to placebo were switched to apremilast 30mg BID for an additional 36 weeks (52 weeks total); Other Names: Otezla CC-10004

Outcome Measures

Primary Outcome Measures

1. Mean Percentage Change From Baseline in the Product of BSA (%) and the sPGA Which is Considered as the Total Psoriasis Severity Index at Week 16 [Baseline to Week 16 (end of phase)]

   BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. The range of BSA*sPGA mean percentage change from baseline to week 16 (end of phase) were -100 to 344.4 and -100 to 100 for the placebo and apremilast groups respectively. Higher scores represented worse outcomes.

Secondary Outcome Measures

1. Mean Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 [Baseline to Week 16 (end of phase)]

   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.

2. Percentage of Participants Who Achieved a sPGA Score of Clear (0) or Almost Clear (1) at Week 16 From Baseline [Baseline to Week 16 (end of phase)]

   The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score.

3. Percentage of Participants Who Achieved a Clear (0) or Very Mild (1) on Patient Global Assessment (PtGA) Scale at Week 16 From Baseline [Baseline to Week 16 (end of phase)]

   The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe).

4. Mean Change From Baseline in Pruritus Visual Analog Scale (VAS) [Baseline to Weeks 1 and 16 (end of phase)]

   The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom.

5. Percentage of Participants With Scalp Psoriasis Who Achieved a Clear (0) or Minimal (1) on Scalp Physician's Global Assessment (ScPGA) Scale at Week 16. [Baseline to Week 16 (end of phase)]

   The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline.

6. Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 16 [Baseline to Week 16 (end of phase)]

   The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment.

7. Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 52 [Baseline to week 52]

   The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment.

8. Mean Percentage Change From Baseline in Psoriasis Area Severity Index Score (PASI) at Week 16 [Baseline to Week 16 (end of phase)]

   The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.

9. Percentage of Participants Who Achieved at Least a 50% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-50 From Baseline at Week 16. [Baseline to Week 16 (end of phase)]

   The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.

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

    The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.

11. Mean Percentage Change From Baseline in the Product of BSA (%) x sPGA at Week 52 [Baseline to Week 52]

    BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score.

12. Percentage of Participants With Scalp Psoriasis Who Were Initially Randomized to Apremilast and Maintained the Scalp Physician's Global Assessment (ScPGA) Response From Week 16 to Week 52. [Week 16 to Week 52]

    The ScPGA will assess scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment with scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA is restricted to the participants with scalp involvement at baseline.

13. Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase [From first dose of study drug to Week 16; maximum duration of exposure was 20.1 weeks during placebo controlled phase]

    Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

14. Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) During the Apremilast-Exposure Phase [Date of first dose of apremilast during the placebo controlled phase or date of first dose of apremilast after week 16; overall maximum duration of exposure was 61.5 weeks during apremilast-exposure phase]

    Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A 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. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the informed consent.

5. Have moderate plaque psoriasis at screening and baseline as defined by

6. BSA (Body Surface Area)5% to 10% and

7. sPGA (Physician's Global Assessment) 3 (moderate) based on a 0 to 5 point scale

8. Must be in general good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, and clinical laboratories.

9. No prior exposure to systemic treatments or biologics for the treatment of psoriatic arthritis, psoriasis, or any other indication that could impact the assessment of psoriasis.

10. 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 additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

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

Exclusion 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. Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.

3. Any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, guttate, inverse, or pustular psoriasis), other than plaque psoriasis.

4. Prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.

5. Pregnant or breast feeding.

6. Active substance abuse or a history of substance abuse within 6 months prior to signing the informed consent.

7. Malignancy or history of malignancy, except for:

8. treated (ie, cured) basal cell or squamous cell in situ skin carcinomas;

9. treated (ie, cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of signing the informed consent.

10. Topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol). Use of phototherapy within 4 weeks prior to randomization.

11. Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).

12. Prolonged sun exposure or use of tanning booths, which may confound the ability to interpret data from the study.

13. Prior treatment with apremilast.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB at Birmingham - The Kirklin Clinic	Birmingham	Alabama	United States	35233
2	Center For Dermatology	Fremont	California	United States	94538
3	Dermatology Research Associates	Los Angeles	California	United States	90045
4	Blue Harbor Dermatology	Newport Beach	California	United States	92663
5	Center for Dermatology and Laser Surgery	Sacramento	California	United States	95819
6	East Bay Rheumatology Medical	San Leandro	California	United States	94578
7	Tien Q. Nguyen MD Inc	Tustin	California	United States	92780
8	UConn Health Center	Farmington	Connecticut	United States	06030
9	Dermatology Associates	Panama City	Florida	United States	32405-4542
10	USF Health Faculty Office Building-FOB	Tampa	Florida	United States	33612
11	Forward Clinical Trials Inc	Tampa	Florida	United States	33624
12	Dermatologic Surgery Specialists, P.C.	Macon	Georgia	United States	31217
13	Shideler Clinical Research Center	Carmel	Indiana	United States	46032
14	Dermatology Specialists, PSC	Louisville	Kentucky	United States	40202
15	DermResearch, PLLC	Louisville	Kentucky	United States	40217
16	Lawrence Green, MD, LLC	Rockville	Maryland	United States	20850
17	Henry Ford Hospital	Detroit	Michigan	United States	48202
18	Las Vegas Skin and Cancer Clinics	Las Vegas	Nevada	United States	89052
19	Psoriasis Treatment Center of Central New Jersey	East Windsor	New Jersey	United States	08520
20	Garden City Dermatology	Garden City	New York	United States	11530
21	Sadick Research Group	New York	New York	United States	10075
22	Dermatology Associates of Rochester PC	Rochester	New York	United States	14623
23	University of Cincinnati	Cincinnati	Ohio	United States	45267-0501
24	Dermatology and Laser Center of Charleston	Charleston	South Carolina	United States	29414
25	University of Utah School of Medicine	Salt Lake City	Utah	United States	84132
26	Dermatology Consultants, Inc.	Lynchburg	Virginia	United States	24501

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

• Reich K, Mrowietz U, Menter A, Griffiths CEM, Bagel J, Strober B, Nunez Gomez N, Shi R, Guerette B, Lebwohl M. Effect of baseline disease severity on achievement of treatment target with apremilast: results from a pooled analysis. J Eur Acad Dermatol Venereol. 2021 Dec;35(12):2409-2414. doi: 10.1111/jdv.17520. Epub 2021 Aug 23.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02425826
• Other Study ID Numbers: CC-10004-PSOR-012; NCT02555826
• First Posted: Apr 24, 2015
• Last Update Posted: Mar 15, 2022
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Amgen: Parapsoriasis; Plaque Psoriasis; CC-10004; Apremilast; Moderate Plaque Psoriasis; Safety
• Additional relevant MeSH terms: Psoriasis; Parapsoriasis; Thalidomide; Apremilast

Study Results

Participant Flow

Recruitment Details	Participants enrolled into this study were those with moderate plaque psoriasis without prior treatment with systemic agents or biologics and were enrolled across 25 study centers in the United States.
Pre-assignment Detail	Participants were randomized in a 2 to 1 ratio to receive apremilast or placebo.

Arm/Group Title	Apremilast	Placebo	Placebo-Apremilast
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 a day (BID) during the placebo-controlled phase (Weeks 0-16)	Participants who were initially randomized to receive placebo were switched to apremilast 30 mg PO BID beginning at Week 16, for an additional 36 weeks (52 weeks total).
Period Title: Placebo-controlled Phase (Week 0 - 16)
STARTED	148	73	0
Intent to Treat	147	73	0
COMPLETED	121	64	0
NOT COMPLETED	27	9	0
Period Title: Placebo-controlled Phase (Week 0 - 16)
STARTED	121	0	64
Received Treatment	121	0	64
COMPLETED	86	0	50
NOT COMPLETED	35	0	14
Period Title: Placebo-controlled Phase (Week 0 - 16)
STARTED	81	0	49
COMPLETED	80	0	49
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Apremilast	Total
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).	Total of all reporting groups
Overall Participants	73	148	221
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	60 82.2%	120 81.1%	180 81.4%
>=65 years	13 17.8%	28 18.9%	41 18.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.1 (13.74)	48.6 (15.41)	49.4 (14.89)
Sex: Female, Male (Count of Participants)
Female	32 43.8%	74 50%	106 48%
Male	41 56.2%	74 50%	115 52%
Body Surface Area (BSA) (percent affected) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent affected]	7.1 (1.75)	7.2 (1.61)	7.2 (1.66)
Static Physician's Global Assessment (sPGA) Score (Number) [Number]
1 = Almost Clear	0 0%	0 0%	0 0%
2 = Mild	0 0%	0 0%	0 0%
3 = Moderate	70 95.9%	144 97.3%	214 96.8%
4 =Severe	3 4.1%	3 2%	6 2.7%
5 = Very Severe	0 0%	0 0%	0 0%
Missing	0 0%	1 0.7%	1 0.5%
Product of BSA and sPGA (psoriasis severity index) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [psoriasis severity index]	21.6 (5.87)	21.8 (5.17)	21.7 (5.40)
Duration of Psoriasis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.85 (12.350)	17.02 (14.138)	15.64 (13.684)
Ethnicity (participants) [Number]
Hispanic or Latino	4 5.5%	13 8.8%	17 7.7%
Not Hispanic or Latino	69 94.5%	134 90.5%	203 91.9%
Unknown	0 0%	1 0.7%	1 0.5%

Outcome Measures

1. Primary Outcome

Title	Mean Percentage Change From Baseline in the Product of BSA (%) and the sPGA Which is Considered as the Total Psoriasis Severity Index at Week 16
Description	BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score. The range of BSA*sPGA mean percentage change from baseline to week 16 (end of phase) were -100 to 344.4 and -100 to 100 for the placebo and apremilast groups respectively. Higher scores represented worse outcomes.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value were included. A missing value at Week 16 was imputed by last observation carried forward. (LOCF).

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	147
Mean (Standard Deviation) [percentage change]	-10.17 (64.043)	-48.07 (43.699)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Based on 2-way ANCOVA with treatment and site as factors and baseline value as covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-39.84
	Confidence Interval	(2-Sided) 95%; -54.39 to -25.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean 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 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	71	144
Mean (Standard Deviation) [units on a scale]	-2.4 (6.62)	-4.8 (5.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments	Based on 2-way ANCOVA with treatment and site as factors and baseline value as covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -3.9 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Who Achieved a sPGA Score of Clear (0) or Almost Clear (1) at Week 16 From Baseline
Description	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 6-point scale, ranging from 0 (clear) to 5 (very severe), with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are averaged and rounded to the nearest whole number to result in the final sPGA score.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with and at least one post-baseline value are included. A missing value at Week 16 was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	148
Number (95% Confidence Interval) [percentage of participants]	9.6 13.2%	30.4 20.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two-sided p-value is based on the Cochran-Mantel-Haenszel test stratified by sites.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	21.0
	Confidence Interval	(2-Sided) 95%; 11.0 to 31.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% confidence intervals (CI) is based on normal approximation

4. Secondary Outcome

Title	Percentage of Participants Who Achieved a Clear (0) or Very Mild (1) on Patient Global Assessment (PtGA) Scale at Week 16 From Baseline
Description	The PtGA response rate is defined as the percentage of participants achieving 0 (clear) or 1 (very mild) on the PtGA scale at Week 16. The PtGA is the assessment by the participant of the overall disease severity at the time of evaluation. The PtGA is a 5-point scale ranging from 0 (clear) to 4 (severe).
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	148
Number (95% Confidence Interval) [percentage of participants]	20.5 28.1%	33.8 22.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0365
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	2-sided p-value is calculated based on Cochran-Mantel-Haenszel test stratified by sites.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	13.7
	Confidence Interval	(2-Sided) 95%; 1.7 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI is based on normal approximation

5. Secondary Outcome

Title	Mean Change From Baseline in Pruritus Visual Analog Scale (VAS)
Description	The Pruritus VAS assessment was conducted at the baseline visit and each post-baseline visit. The participant was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (0) represents no itch, and the right-hand boundary (100) represents itch as severe as can be imagined. The distance from the mark to the left-hand boundary will be recorded. The Pruritus VAS score ranges from 0 to 100. Higher scores correspond to more severe symptom.
Time Frame	Baseline to Weeks 1 and 16 (end of phase)

Outcome Measure Data

Analysis Population Description

ITT population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	148
Week 1	-9.6 (21.50)	-13.9 (20.00)
Week 16	-10.2 (30.73)	-19.2 (26.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments	The treatment comparison was only done for Week 16; End of Phase
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	ANCOVA
	Comments	Based on 2-way ANCOVA with treatment and site as factors and baseline value as covariate.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-11.6
	Confidence Interval	(2-Sided) 95%; -18.8 to -4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Scalp Psoriasis Who Achieved a Clear (0) or Minimal (1) on Scalp Physician's Global Assessment (ScPGA) Scale at Week 16.
Description	The ScPGA assessed scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment. Scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA was restricted to the participants with scalp involvement at baseline.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population with scalp psoriasis who were randomized. Participants with at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	55	112
Number (95% Confidence Interval) [percentage of participants]	38.2 52.3%	50.0 33.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0463
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	p-value was based on 2-sided CMH tests stratified by sites.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	11.8
	Confidence Interval	(2-Sided) 95%; -4.0 to 27.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI is based on normal approximation.

7. Secondary Outcome

Title	Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 16
Description	The TSQM version II is an 11-question self-administered instrument to understand a participation's satisfaction with the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score mean indicates higher satisfaction with treatment.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	146
TSQM-Effectiveness	38.81 (25.843)	57.25 (26.484)
TSQM-Side Effects	75.00 (32.428)	78.50 (20.858)
TSQM-Convenience	65.68 (16.650)	66.93 (21.216)
TSQM-Global Satisfaction	48.74 (25.673)	63.24 (23.624)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments	TSQM-Effectiveness
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANOVA
	Comments	Based on 2-way ANOVA with treatment and site as factors.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	17.80
	Confidence Interval	(2-Sided) 95%; 10.36 to 25.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments	TSQM - Side Effects
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3433
	Comments
	Method	ANOVA
	Comments	Based on 2-way ANOVA with treatment and site as factors.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.00
	Confidence Interval	(2-Sided) 95%; -5.40 to 15.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments	TSMQ-Convenience
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6250
	Comments
	Method	ANOVA
	Comments	Based on 2-way ANOVA with treatment and site as factors.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; -4.25 to 7.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments	TSQM-Global Satisfaction
	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	Mean Difference (Final Values)
	Estimated Value	14.07
	Confidence Interval	(2-Sided) 95%; 7.16 to 20.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Treatment Satisfaction Questionnaire for Medication (TSQM) Version II at Week 52
Description	The TSQM version II is an 11-question self-administered instrument to understand a participants satisfaction on the current therapy. The TSQM scale comprises four domains, on which participants evaluate their medication (i.e., effectiveness, side effects, convenience and global satisfaction. TSQM scores range from 0 to 100 for each domain; a higher score indicates higher satisfaction with treatment.
Time Frame	Baseline to week 52

Outcome Measure Data

Analysis Population Description

Apremilast participants who entered and were treated in the apremilast extension phase.

Arm/Group Title	Placebo-Apremilast	Apremilast
Arm/Group Description	Participants who were initially randomized to receive placebo were switched to apremilast 30 mg PO BID beginning at Week 16, for an additional 36 weeks (52 weeks total).	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	64	121
TSQM-Effectiveness	57.68 (26.879)	54.13 (26.898)
TSQM-Side Effects	77.29 (27.541)	75.45 (24.904)
TSQM-Convenience	72.74 (17.222)	71.76 (19.359)
TSQM-Global Satisfaction	59.24 (27.941)	59.92 (27.053)

9. Secondary Outcome

Title	Mean Percentage Change From Baseline in Psoriasis Area Severity Index Score (PASI) at Week 16
Description	The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	147
Mean (Standard Deviation) [percentage change]	-3.87 (79.441)	-40.72 (49.523)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	Based on 2-way ANCOVA with treatment and site as factors and baseline value as covariate
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-37.0
	Confidence Interval	(2-Sided) 95%; -54.08 to -19.91
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants Who Achieved at Least a 50% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-50 From Baseline at Week 16.
Description	The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	148
Number (95% Confidence Interval) [percentage of participants]	24.7 33.8%	53.4 36.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	2-sided p-value is calculated based on Cochran-Mantel-Haenszel test stratified by sites.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	29.1
	Confidence Interval	(2-Sided) 95%; 16.3 to 41.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% CI is based on normal approximation

11. Secondary Outcome

Title	Percentage of Participants Who Achieved at Least a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI)-75 From Baseline at Week 16
Description	The PASI score is 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. 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). PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.
Time Frame	Baseline to Week 16 (end of phase)

Outcome Measure Data

Analysis Population Description

The ITT population consisted of all participants who were randomized. Participants with a baseline value and at least one post-baseline value are included. A missing value at Week 16 (end of phase) was imputed by LOCF.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	148
Number (95% Confidence Interval) [percentage of participants]	8.2 11.2%	21.6 14.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0136
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	2-sided Cochran-Mantel-Haenszel test stratified by sites.
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	13.5
	Confidence Interval	(2-Sided) 95%; 4.4 to 22.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI is based on normal approximation.

12. Secondary Outcome

Title	Mean Percentage Change From Baseline in the Product of BSA (%) x sPGA at Week 52
Description	BSA is a measurement of involved skin. The overall BSA affected by psoriasis is 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. The sPGA is a 6-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), 5 (very severe) incorporating a separate assessment of the severity of the three primary signs of the plaques of all involved areas: erythema, scaling and plaque elevation with an overall sPGA calculated as (E + I + D)/3. Scores for each assessment are rounded to the nearest whole number to result in the final score.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Apremilast participants who entered and were treated in the apremilast extension phase.

Arm/Group Title	Placebo-Apremilast	Apremilast
Arm/Group Description	Participants who were initially randomized to receive placebo were switched to apremilast 30 mg PO BID beginning at Week 16, for an additional 36 weeks (52 weeks total).	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	64	121
Mean (Standard Deviation) [percentage change]	-42.23 (93.211)	-55.45 (44.619)

13. Secondary Outcome

Title	Percentage of Participants With Scalp Psoriasis Who Were Initially Randomized to Apremilast and Maintained the Scalp Physician's Global Assessment (ScPGA) Response From Week 16 to Week 52.
Description	The ScPGA will assess scalp involvement, if present at baseline. The 6-point ScPGA scale includes three dimensions (Plaque Thickening, Scaling, and Erythema) and a global assessment with scores range from 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), to 5 (very severe). Analysis of ScPGA is restricted to the participants with scalp involvement at baseline.
Time Frame	Week 16 to Week 52

Outcome Measure Data

Analysis Population Description

Participants who were initially randomized to apremilast and continued through week 52.

Arm/Group Title	Apremilast
Arm/Group Description	Apremilast 30 mg tablets orally twice daily (BID) weeks 0 to 52.
Measure Participants	148
Responder status at Week 16	50.0 68.5%
Responder status maintained at Week 52	80.4 110.1%

14. Secondary Outcome

Title	Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase
Description	Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Time Frame	From first dose of study drug to Week 16; maximum duration of exposure was 20.1 weeks during placebo controlled phase

Outcome Measure Data

Analysis Population Description

The safety population includes all participants who were randomized and received at least one dose of study drug.

Arm/Group Title	Placebo	Apremilast
Arm/Group Description	Participants were initially randomized to identically matching placebo (PBO) tablets BID during the placebo-controlled phase (Weeks 0-16)	Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the placebo-controlled phase (Weeks 0-16).
Measure Participants	73	147
≥ At Least 1 TEAE	35 47.9%	92 62.2%
≥ 1 Drug-related TEAE	21 28.8%	71 48%
≥ At Least 1 Severe TEAE	1 1.4%	3 2%
≥ At Least 1 Serious TEAE	0 0%	3 2%
≥ 1 Serious Drug-related TEAE	0 0%	0 0%
≥ 1 TEAE leading to drug withdrawal	3 4.1%	5 3.4%
≥ 1 TEAE Leading to drug interruption	3 4.1%	9 6.1%
Any TEAE leading to death	0 0%	0 0%

15. Secondary Outcome

Title	Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) During the Apremilast-Exposure Phase
Description	Treatment-Emergent Adverse Events (TEAEs) are defined as any AEs that begin or worsen on or after the start of study drug through 28 days after the last dose of study drug or study treatment discontinuation date, whichever was later. 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/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
Time Frame	Date of first dose of apremilast during the placebo controlled phase or date of first dose of apremilast after week 16; overall maximum duration of exposure was 61.5 weeks during apremilast-exposure phase

Outcome Measure Data

Analysis Population Description

The safety population includes all participants who were randomized and received at least one dose of study drug; apremilast participants as treated.

Arm/Group Title	Apremilast
Arm/Group Description	Participants treated with placebo initially, completed Week 16, entered and treated with apremilast during the apremilast open-label extension phase.
Measure Participants	211
≥ At Least 1 TEAE	142 194.5%
≥ 1 Drug-related TEAE	98 134.2%
≥ At Least 1 Severe TEAE	5 6.8%
≥ At Least 1 Serious TEAE	10 13.7%
≥ 1 Serious Drug-related TEAE	1 1.4%
≥ 1 TEAE leading to drug withdrawal	14 19.2%
≥ 1 TEAE Leading to drug interruption	27 37%
Any TEAE leading to death	0 0%

Adverse Events

Time Frame	Adverse events are reported for the 16-week PBO-controlled and the apremilast extension phase and monitored from the date of the first dose of apremilast to 12 January2017; maximum duration of exposure was 61.5 weeks during apremilast-exposure phase.
Adverse Event Reporting Description	The difference between participants enrolled (148) in the apremilast group and treated (147) lies in one participant, who was randomized in error.
Arm/Group Title	Placebo-Controlled Phase: Apremilast (Weeks 0-16)		Placebo-Controlled Phase: Placebo (Weeks 0-16)		Extension Phase: APR/APR and Placebo/APR (Weeks 0-52)
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 initially randomized to identically matching placebo tablets PO BID during the placebo-controlled phase. (Weeks 0-16).		Includes participants initially randomized to apremilast tablets BID in the placebo controlled phase and continued on apremilast (Apremilast/Apremilast), as well as those who were initially randomized to placebo and switched at week 16 (Placebo/Apremilast) to Apremilast 30 mg tablets BID during weeks 16-52
All Cause Mortality
	Placebo-Controlled Phase: Apremilast (Weeks 0-16)		Placebo-Controlled Phase: Placebo (Weeks 0-16)		Extension Phase: APR/APR and Placebo/APR (Weeks 0-52)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo-Controlled Phase: Apremilast (Weeks 0-16)		Placebo-Controlled Phase: Placebo (Weeks 0-16)		Extension Phase: APR/APR and Placebo/APR (Weeks 0-52)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/147 (2%)		0/73 (0%)		10/211 (4.7%)
Hepatobiliary disorders
Cholelithiasis	1/147 (0.7%)		0/73 (0%)		1/211 (0.5%)
Infections and infestations
Diverticulitis	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Pneumonia	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Pyelonephritis	1/147 (0.7%)		0/73 (0%)		1/211 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinoma	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Keratoacanthoma	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Nervous system disorders
Cerebrovascular accident	1/147 (0.7%)		0/73 (0%)		1/211 (0.5%)
Dizziness	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Psychiatric disorders
Suicide attempt	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Renal and urinary disorders
Nephrolithiasis	1/147 (0.7%)		0/73 (0%)		1/211 (0.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/147 (0%)		0/73 (0%)		1/211 (0.5%)
Other (Not Including Serious) Adverse Events
	Placebo-Controlled Phase: Apremilast (Weeks 0-16)		Placebo-Controlled Phase: Placebo (Weeks 0-16)		Extension Phase: APR/APR and Placebo/APR (Weeks 0-52)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/147 (49.7%)		23/73 (31.5%)		101/211 (47.9%)
Gastrointestinal disorders
Diarrhoea	43/147 (29.3%)		12/73 (16.4%)		59/211 (28%)
Nausea	26/147 (17.7%)		7/73 (9.6%)		40/211 (19%)
Vomiting	9/147 (6.1%)		2/73 (2.7%)		12/211 (5.7%)
Infections and infestations
Nasopharyngitis	5/147 (3.4%)		2/73 (2.7%)		22/211 (10.4%)
Upper respiratory tract infection	10/147 (6.8%)		3/73 (4.1%)		15/211 (7.1%)
Metabolism and nutrition disorders
Decreased appetite	6/147 (4.1%)		4/73 (5.5%)		11/211 (5.2%)
Nervous system disorders
Headache	30/147 (20.4%)		8/73 (11%)		32/211 (15.2%)

Limitations/Caveats

[Not Specified]

More Information

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.