Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Patients With Moderate-To-Severe Plaque-Type Psoriasis

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01988103
• Collaborator: (none)
• Enrollment: 254
• Locations: 56
• Arms: 3
• Actual Duration (Months): 29.2
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will test the clinical effectiveness and safety of two orally administered doses of apremilast compared to placebo in Japanese patients with moderate-to-severe plaque-type psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis; Psoriatic Arthritis; Psoriasis Arthropatica	Drug: Apremilast; Drug: Apremilast; Drug: Placebo	Phase 2

Detailed Description

This is a phase 2b, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of apremilast 20 mg twice a day (BID), apremilast 30 mg BID, and placebo in Japanese participants with moderate to severe plaque psoriasis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 254 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Subjects With Moderate-To-Severe Plaque-Type Psoriasis
• Actual Study Start Date: Jul 9, 2013
• Actual Primary Completion Date: Nov 20, 2014
• Actual Study Completion Date: Dec 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apremilast 20mg Apremilast 20 mg tablets orally twice a day (BID)	Drug: Apremilast; 20 mg tablet BID for 68 weeks; Other Names: CC-10004 Otzela ; Drug: Placebo; Placebo tablet BID for 16 weeks
Experimental: Apremilast 30mg Apremilast 30 mg tablets orally BID	Drug: Apremilast; 20 mg tablet BID for 68 weeks; Other Names: CC-10004 Otzela ; Drug: Placebo; Placebo tablet BID for 16 weeks
Placebo Comparator: Placebo Identically-appearing placebo tablets BID for 16 weeks followed by participants being re-randomized in a blinded fasion to apremilast 20 mg or 30mg tablets BID for 52 weeks	Drug: Placebo; Placebo tablet BID for 16 weeks

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

   The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. It does not compare assessments across visits or rely on investigator recall or prior disease. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examines all of the lesions on the participant and assigns a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equals the overall sPGA score.

2. Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) at Week 16 [Baseline to Week 16]

   BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the subject's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area.

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

   The PASI 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. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. The PASI scores range from 0 to 72, with higher scores reflecting a greater disease severity.

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

   PASI-50 response is the percentage of participants who achieved at least a 50% 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.

5. Change From Baseline in Pruritus Visual Analogue Scale 100-mm (VAS) at Week 16 [Baseline to Week 16]

   The pruritus visual analog scale (VAS) was 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? Higher scores correspond to more severe symptom or disease. The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no itch at all and the right-hand boundary represents the worst itch imaginable. The distance from the vertical line to the left-hand boundary is recorded. VAS scores range from 0 to 100 mm, where higher scores correspond to worse pruritis (itch).

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

   Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains 10 items dealing with the participants 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 has a possible range from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.

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

   SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It 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 quality of life (better functioning)

8. Number of Participants Who Achieved an American College of Rheumatology Criteria (ACR) 20% Improvement (ACR 20) [Baseline to Week 16]

   The ACR 20 is defined as a 20% improvement in joint tenderness (78 joint count) and joint swelling scores (76 joint count) compared to baseline plus 20% improvements in 3 of the following 5 assessments (compared to baseline): subject global assessment of disease activity (measured on a 100-mm visual analog scale [VAS]); physician global assessment of disease activity (measured on a 100-mm VAS); subject self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI] score); subject assessment of pain (measured on a 100-mm VAS); and CRP level.

9. Percent Change From Baseline Psoriatic Arthritis Pain Visual Analogue Scale (VAS) [Baseline to Week 16]

   Change from baseline in psoriatic arthritis pain 100-mm VAS; The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no pain at all and the right-hand boundary represents the worst possible pain. The distance from the vertical line to the left-hand boundary is recorded.

10. Percent Change From Baseline in Physical Function Assessment Using the Health Assessment Questionnaire Disability Index (HAQ-DI) [Baseline to Week 16]

    Change from baseline in physical function assessment using HAQ-DI; The HAQ-DI is a 20-question, self-administered instrument that measures the subject's functional ability on a 4-level difficulty scale (0-3, with 0 representing normal or no difficulty; and 3 representing inability to perform). Eight categories of functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.

11. Number of Participants With Adverse Events (AE) in the Placebo Controlled Phase [Baseline to Week 16]

    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.

12. Number of Participants With Adverse Events (AE) in the During the Apremilast-exposure Period [From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo who were re-randomized at Week 16) until 28 days after the last dose of apremilast.]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female Japanese participants greater than or equal to 20 years of age.

• Diagnosis of chronic, stable plaque psoriasis for at least 6 months prior to screening as defined by: Psoriasis Area Severity Index (PASI) score ≥ 12 and BSA ≥ 10%.

• Psoriasis which is considered inappropriate for topical therapy (based on severity of disease and extent of affected area) or has not been adequately controlled or treated by topical therapy in spite of at least 4 weeks of prior therapy with at least one topical medication for psoriasis or per label.

• In otherwise good health based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology, immunology, and urinalysis.

Exclusion Criteria:

• Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the participant at unacceptable risk or confound the ability to interpret the data in the study.

Prior medical history of suicide attempt or major psychiatric illness requiring hospitalization within the last 3 years

• Pregnant or breastfeeding.

• History of or ongoing chronic or recurrent infectious disease.

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

• Clinically significant abnormality on 12-lead ECG or on chest radiograph at screening.

• History of human immunodeficiency virus (HIV) infection or have congenital or acquired immunodeficiencies (eg, Common Variable Immunodeficiency).

• Hepatitis B surface antigen or hepatitis B core antibody positive at screening; positive for antibodies to hepatitis C at screening.

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

• Psoriasis flare within 4 weeks of screening.

• Topical therapy within 2 weeks prior to randomization or systemic therapy for psoriasis or psoriatic arthritis within 4 weeks prior to randomization.

• Use of etretinate within 2 years prior to randomization for females of child bearing potential (FCBP) or within 6 months for males, and within 4 weeks prior to randomization for non-FCBP.

• Use of phototherapy: Ultraviolet light B (UVB), Psoralens and long-wave ultraviolet radiation (PUVA) within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet light sources.

• Use of adalimumab, etanercept, certolizumab pegol, abatacept, tocilizumab, golimumab or infliximab within 12 weeks prior to randomization; use of ustekinumab, alefacept or briakinumab within 24 weeks prior to randomization.

• Any investigational drug within 4 weeks prior to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ekihigashi Hifuka Clinic	Fukuoka-shi	Fukuoka	Japan	812-0013
2	Tsutsui Clinic Dermatology & Plastic Surgery	Fukuoka-shi	Fukuoka	Japan	813-0042
3	Yano Hifuka Hinyokika Clini	Fukuoka-shi	Fukuoka	Japan	814-0013
4	Fukuoka University Hospital	Fukuoka-shi	Fukuoka	Japan	814-0180
5	HATAMOTO Derma Clinic	Fukuoka-shi	Fukuoka	Japan	815-0075
6	Tomoko Matsuda Dermatological Clinic	Fukuoka-shi	Fukuoka	Japan	819-0167
7	TASHIRO Dermatological Clinic	Iizuka-shi	Fukuoka	Japan	820-0040
8	Okubo Skin Care and Clinic	Itoshima-shi	Fukuoka	Japan	819-1108
9	Matsuda Dermatology Clinic For Skin, Hair, Nail Diseases	Itoshima-shi	Fukuoka	Japan	819-1116
10	Kyusyu Rosai Hospital	Kitakyushu-shi	Fukuoka	Japan	800-0296
11	Kitakyushu Municipal Medical Center	Kitakyushu	Fukuoka	Japan	802-0077
12	Kyushu Kosei Nenkin Hospital	Kitakyushu	Fukuoka	Japan	806-8501
13	Kurume University Hospital	Kurume	Fukuoka	Japan	830-0011
14	Matsuo Clinic	Nishi-Ku	Fukuoka	Japan	819-0373
15	Yame General Hospital	Yame	Fukuoka	Japan	834-0034
16	Kokubu Medical Office Abashiri Dermatology Clinic	Abashiri-shi	Hokkaido	Japan	093-0016
17	Chitose Dermatology Plastic Surgery Clinic	Chitose-shi	Hokkaido	Japan	066-0021
18	Asanuma Dermatology Clinic	Chitose-shi	Hokkaido	Japan	066-0064
19	Kokubu Dermatology	Kitami-shi	Hokkaido	Japan	090-0832
20	Sapporo Skin Clinic	Sapporo-shi	Hokkaido	Japan	060-0063
21	Fukuzumi Dermatology Clinic	Sapporo-shi	Hokkaido	Japan	062-0042
22	Kobe City Medical Center	Kobe City	Hyogo	Japan	653-0013
23	Hitachi General Hospital	Hitachi	Ibaraki	Japan	317-0077
24	Tokyo Medical University Ibaraki Medical Center	Inashiki-gun	Ibaraki	Japan	300-0395
25	Kanto Rosai Hospital	Kawasaki City	Kanagawa	Japan	211-8510
26	Kawasaki Saiwai Clinic	Kawasaki-shi	Kanagawa	Japan	212-0016
27	Teikyo University School of Medicine University Hospital	Kawasaki	Kanagawa	Japan	213-8507
28	Sagamihara National Hospital	Sagamihara	Kanagawa	Japan	252-0392
29	Queen's Square Medical Facilities	Yokohama-shi	Kanagawa	Japan	220-6208
30	Yokohama City University Hospital	Yokohama	Kanagawa	Japan	213-8507
31	Nomura Dermatology Clinic	Yokohoma City	Kanagawa	Japan	221-0825
32	Yokosuka Kyosai Hospital	Yokosuka	Kanagawa	Japan	238-8558
33	Kumamoto Shinto General Hospital	Kumamoto City	Kumamoto	Japan	862-0975
34	Kosumi lin	Kumamoto-shi	Kumamoto	Japan	860-0016
35	Kume Derma Clinic	Sakai-Shi	Osaka	Japan	593-8324
36	SANRUI Dermatology	Saitama-shi	Saitama	Japan	330-0854
37	Jichi Medical University Hospital	Shimotsuke-shi	Tochigi	Japan	329-0498
38	Sugai Dermatologist Park Side Clinic	Utsunomiya-shi	Tochigi	Japan	321-0954
39	Kayaba Dermatology Clinic	Cyu-o-ku	Tokyo	Japan	103-0016
40	Tokai University School of Medicine	Hachioji	Tokyo	Japan	192-0032
41	Inagi Municipal Hospital	Inagi	Tokyo	Japan	206-2801
42	TSUTSUMI Clinic	Itabasi-Ku	Tokyo	Japan	174-0071
43	Koto Hospital	Koto-ku	Tokyo	Japan	136-0072
44	Maruyama Dermatology Clinic	Koto-ku	Tokyo	Japan	136-0074
45	OIZUMI HANAWA Clinic	Nerima-ku	Tokyo	Japan	178-0063
46	Kitahara Dermatology Clinic	Setagaya-ku	Tokyo	Japan	158-0094
47	NAOKO Dermatology Clinic	Setagaya-ku	Tokyo	Japan	158-0097
48	Mita Dermatology Clinic	Shiba Minato-k	Tokyo	Japan	108-0014
49	NTT Medical Center Tokyo	Shinagawa-ku	Tokyo	Japan	141-8625
50	Tokyo Medical University Hospital	Shinjyuku-ku	Tokyo	Japan	160-0023
51	Taneda Dermatology Clinic	Suginami-ku	Tokyo	Japan	166-0015
52	Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital	Tachikawa	Tokyo	Japan	190-8531
53	Shakaihoken Simonoseki Kosei Hospital	Shimonoseki-shi	Yamaguchi	Japan	750-0061
54	Matsuo Clinic	Fukuoka		Japan	719-0373
55	AMC Nishiumeda Clinic	Osaka		Japan	530-0001
56	Tokyo Center Clinic	Tokyo		Japan	103-0028

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ohtsuki M, Kubo H, Morishima H, Goto R, Zheng R, Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol. 2018 Sep;45(9):1053-1062. doi: 10.1111/1346-8138.14504. Epub 2018 Jun 15.
• Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, Petric R, Maroli A, Nemoto O. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. J Dermatol. 2017 Aug;44(8):873-884. doi: 10.1111/1346-8138.13829. Epub 2017 Apr 9.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01988103
• Other Study ID Numbers: CC-10004-PSOR-011
• First Posted: Nov 20, 2013
• Last Update Posted: May 7, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Amgen: Psoriasis; Psoriatic Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Psoriatic; Psoriasis; Thalidomide; Apremilast

Study Results

Participant Flow

Recruitment Details	Participants must have had a diagnosis of chronic, stable plaque psoriasis at least 6 months prior to screening and which was considered inappropriate for topical therapy (e.g, based on the severity of the disease and extent of affected area) or could not be adequately controlled/treated with topical therapy to qualify for the study.
Pre-assignment Detail	Treatment assignments were stratified according to whether the participants had a psoriatic arthritis (PsA) diagnosis by Classification Criteria for Psoriatic Arthritis (CASPAR) criteria (yes/no) at screening, whether they participated in the sparse pharmacokinetic (PK) sampling, and whether they had participated in the intensive PK sampling.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Placebo-Apremilast 20 mg	Placebo-Apremilast 30 mg
Arm/Group Description	Participants who were initially randomized to identically matching placebo (PBO) by mouth (PO) twice a day (BID) during the Placebo-controlled Phase (Weeks 0-16).	Participants were randomized to apremilast 20 mg PO BID during the Placebo-controlled Phase (Weeks 0-16) and remained on apremilast 20 mg PO BID dosing during the active treatment phase (weeks 16-68).	Participants were randomized to apremilast 30 mg PO BID during the Placebo-controlled Phase (Weeks 0-16) and remained on apremilast 30 mg PO BID dosing during the active treatment phase (weeks 16-68).	Participants who were initially randomized to identically matching PBO PO BID during the Placebo-controlled Phase (weeks 0-16) were re-randomized to apremilast 20 mg PO BID and remained on apremilast 20 mg PO BID dosing during the active treatment phase (weeks 16-68).	Participants who were initially randomized to identically matching PBO PO BID during the Placebo-controlled Phase (weeks 0-16) were re-randomized to apremilast 30 mg PO BID and continued dosing with apremilast 30 mg PO BID during the active treatment phase (weeks 16-68).
Period Title: Placebo-Controlled Phase Week 0-16
STARTED	84	85	85	0	0
COMPLETED	72	69	76	0	0
NOT COMPLETED	12	16	9	0	0
Period Title: Placebo-Controlled Phase Week 0-16
STARTED	0	69	76	36	35
COMPLETED	0	56	65	33	30
NOT COMPLETED	0	13	11	3	5
Period Title: Placebo-Controlled Phase Week 0-16
STARTED	12	82	83	36	33
COMPLETED	12	79	82	36	33
NOT COMPLETED	0	3	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Total
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.	Total of all reporting groups
Overall Participants	84	85	85	254
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.3 (11.98)	52.2 (12.54)	51.7 (12.73)	50.8 (12.49)
Sex: Female, Male (Count of Participants)
Female	22 26.2%	16 18.8%	14 16.5%	52 20.5%
Male	62 73.8%	69 81.2%	71 83.5%	202 79.5%
Region of Enrollment (Number) [Number]
Japan	84 100%	85 100%	85 100%	254 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieved a 75% Improvement (Response) From Baseline in the Psoriasis Area and Severity Index (PASI-75) at Week 16
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 was missing.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the Last observation carried forward (LOCF) method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Number [percentage of participants]	7.1 8.5%	23.5 27.6%	28.2 33.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	16.4
	Confidence Interval	(2-Sided) 95%; 5.8 to 27.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	21.1
	Confidence Interval	(2-Sided) 95%; 10.1 to 32.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Achieved a Static Physician's Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Point Reduction From Baseline to Week 16
Description	The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. It does not compare assessments across visits or rely on investigator recall or prior disease. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examines all of the lesions on the participant and assigns a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equals the overall sPGA score.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT population with a sPGA greater than 2 at baseline. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	68	71	71
Number [percentage of participants]	8.8 10.5%	23.9 28.1%	29.6 34.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0165
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	15.1
	Confidence Interval	(2-Sided) 95%; 3.1 to 27.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	20.8
	Confidence Interval	(2-Sided) 95%; 8.2 to 33.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Missing values were imputed using the LOCF method.

3. Secondary Outcome

Title	Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) 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 subject's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Least Squares Mean (Standard Error) [percent change]	7.5 (5.56)	-21.6 (5.52)	-30.5 (5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.1
	Confidence Interval	(2-Sided) 95%; -44.5 to -13.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-38.0
	Confidence Interval	(2-Sided) 95%; -53.4 to -22.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

4. Secondary Outcome

Title	Percent Change From Baseline in the Psoriasis Area and Severity Index (PASI) Score
Description	The PASI 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. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. The PASI scores range from 0 to 72, with higher scores reflecting a greater disease severity.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Least Squares Mean (Standard Error) [percent change]	-3.7 (5.55)	-33.1 (5.51)	-43.1 (5.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-29.5
	Confidence Interval	(2-Sided) 95%; -44.9 to -14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-39.5
	Confidence Interval	(2-Sided) 95%; -54.9 to -24.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

5. Secondary Outcome

Title	Percentage of Participants Who Achieved a 50% Improvement From Baseline (Response) Reduction in the PASI-50 at Week 16
Description	PASI-50 response is the percentage of participants who achieved at least a 50% 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

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Number [percentage of participants]	21.4 25.5%	41.2 48.5%	50.6 59.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	19.7
	Confidence Interval	(2-Sided) 95%; 6.1 to 33.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	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	Difference
	Estimated Value	29.2
	Confidence Interval	(2-Sided) 95%; 15.4 to 42.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Pruritus Visual Analogue Scale 100-mm (VAS) at Week 16
Description	The pruritus visual analog scale (VAS) was 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? Higher scores correspond to more severe symptom or disease. The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no itch at all and the right-hand boundary represents the worst itch imaginable. The distance from the vertical line to the left-hand boundary is recorded. VAS scores range from 0 to 100 mm, where higher scores correspond to worse pruritis (itch).
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Least Squares Mean (Standard Error) [units on a scale]	7.1 (2.86)	-7.5 (2.84)	-17.7 (2.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.6
	Confidence Interval	(2-Sided) 95%; -22.6 to -6.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-24.8
	Confidence Interval	(2-Sided) 95%; -32.7 to -16.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate. Missing values were imputed using the LOCF method.

7. Secondary Outcome

Title	Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16
Description	Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains 10 items dealing with the participants 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 has a possible range from 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

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized. Missing values were imputed using the LOCF method.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Least Squares Mean (Standard Error) [units on a scale]	1.3 (0.53)	-0.5 (0.53)	-2.2 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0204
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95%; -3.2 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.5
	Confidence Interval	(2-Sided) 95%; -4.9 to -2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

8. Secondary Outcome

Title	Change From Baseline in Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16
Description	SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It 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 quality of life (better functioning)
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

mITT population consisted of all participants who were randomized and received at least one dose of IP. Participants were included in the treatment group in which they were randomized.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
Least Squares Mean (Standard Error) [units on a scale]	-1.59 (0.953)	-0.71 (0.953)	0.27 (0.948)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5149
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; -1.78 to 3.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1693
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.85
	Confidence Interval	(2-Sided) 95%; -0.79 to 4.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	2-sided 95% CI and p-values were based on an analysis of covariance model with treatment arm as a factor and baseline value as a covariate. Means (LS Means) and p-values were adjusted by covariate.

9. Secondary Outcome

Title	Number of Participants Who Achieved an American College of Rheumatology Criteria (ACR) 20% Improvement (ACR 20)
Description	The ACR 20 is defined as a 20% improvement in joint tenderness (78 joint count) and joint swelling scores (76 joint count) compared to baseline plus 20% improvements in 3 of the following 5 assessments (compared to baseline): subject global assessment of disease activity (measured on a 100-mm visual analog scale [VAS]); physician global assessment of disease activity (measured on a 100-mm VAS); subject self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI] score); subject assessment of pain (measured on a 100-mm VAS); and CRP level.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Due to the small sample size in the study for the ACR 20 % improvement, the analysis was not conducted. The decision not to perform the analysis was authorized by the lead therapeutic executive and there is no data available to analyze. No resources are available to conduct the ACR 20% improvement endpoint for this population.

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	0	0	0

10. Secondary Outcome

Title	Percent Change From Baseline Psoriatic Arthritis Pain Visual Analogue Scale (VAS)
Description	Change from baseline in psoriatic arthritis pain 100-mm VAS; The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no pain at all and the right-hand boundary represents the worst possible pain. The distance from the vertical line to the left-hand boundary is recorded.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Due to the small sample size in the study for change from baseline in psoriatic arthritis pain VAS, the analysis was not conducted. The decision not to perform the analysis was authorized by the lead therapeutic executive and there is no data to analyze. No resources are available to conduct the analysis for the end point.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg PO BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg PO BID during the 16-week placebo controlled phase.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Percent Change From Baseline in Physical Function Assessment Using the Health Assessment Questionnaire Disability Index (HAQ-DI)
Description	Change from baseline in physical function assessment using HAQ-DI; The HAQ-DI is a 20-question, self-administered instrument that measures the subject's functional ability on a 4-level difficulty scale (0-3, with 0 representing normal or no difficulty; and 3 representing inability to perform). Eight categories of functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.
Time Frame	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

Due to the small sample size for the change from baseline in physical function assessment using the HAQ-DI, the analysis was not conducted. The decision not to perform the analysis was authorized by the lead therapeutic executive and there is no data available to analyze. No resources are available to conduct the analysis for the end point.

Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description	Participants initially randomized to identically matching placebo PO BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg PO BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg PO BID during the 16-week placebo controlled phase.
Measure Participants	0	0	0

12. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) in 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	Baseline to Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants initially randomized to identically matching placebo during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 20mg BID during the 16-week placebo controlled phase.	Participants initially randomized to apremilast 30mg BID during the 16-week placebo controlled phase.
Measure Participants	84	85	85
≥ At least 1 TEAE	35 41.7%	49 57.6%	44 51.8%
≥ 1 Drug-related TEAE	8 9.5%	18 21.2%	25 29.4%
≥ At least 1 Severe TEAE	1 1.2%	4 4.7%	0 0%
≥ 1 Serious TEAE	0 0%	4 4.7%	0 0%
Any Serious Drug-related TEAE	0 0%	2 2.4%	0 0%
≥ 1 TEAE leading to Drug Interruption	2 2.4%	2 2.4%	0 0%
≥ 1 TEAE Leading to Drug Withdrawal	4 4.8%	10 11.8%	6 7.1%
≥ 1 TEAE Leading to Death	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) in the During the Apremilast-exposure Period
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	From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo who were re-randomized at Week 16) until 28 days after the last dose of apremilast.

Outcome Measure Data

Analysis Population Description

All participants who received apremilast at any time during the trial.

Arm/Group Title	Apremilast 20mg	Apremilast 30mg
Arm/Group Description	Participants who received their first dose of apremilast 20 mg PO BID during the placebo-controlled phase or those who were originally randomized to placebo and were subsequently re-randomized to apremilast 20 mg PO BID.	Participants who received their first dose of apremilast 30 mg PO BID during the placebo-controlled phase or those who were originally randomized to placebo and were subsequently re-randomized to apremilast 30 mg PO BID.
Measure Participants	121	120
≥ At Least 1 TEAE	94 111.9%	89 104.7%
≥ 1 Drug-related TEAR	34 40.5%	37 43.5%
≥ At Least 1 Severe TEAE	12 14.3%	2 2.4%
≥ 1 Serious TEAE	11 13.1%	2 2.4%
Any Serious Drug-related TEAE	5 6%	0 0%
≥ 1 TEAE leading to Drug Interruption	6 7.1%	2 2.4%
≥ 1 TEAE Leading to Drug Withdrawal	19 22.6%	10 11.8%
≥ 1 TEAE Leading to Death	1 1.2%	0 0%

Adverse Events

Time Frame	AEs are reported for the 16-week placebo-controlled phase and up to 68 weeks for those who received apremilast during the study; TEAEs were recorded from the date of the first dose of IP received to no later than 28 days after the last dose of IP
Arm/Group Title	Placebo (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-16)		Apremilast 30mg BID (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-68)		Apremilast 30mg BID (Weeks 0-68)
Arm/Group Description	Participants initially randomized to identically matching placebo (PBO) by mouth (PO) twice a day (BID) during the Placebo-controlled Phase (Weeks 0-16).		Participants initially randomized to receive apremilast 20 mg BID PO during the Placebo-controlled Phase (Weeks 0-16).		Participants initially randomized to apremilast 30 mg BID PO during the Placebo-controlled Phase (Weeks 0-16).		Participants who received 20 mg PO BID apremilast, regardless of when the apremilast exposure started (at Week 0 or at Week 16 up until Week 68.		Participants who received 30 mg PO BID apremilast, regardless of when the apremilast exposure started (at Week 0 or at Week 16 up until Week 68
All Cause Mortality
	Placebo (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-16)		Apremilast 30mg BID (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-68)		Apremilast 30mg BID (Weeks 0-68)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-16)		Apremilast 30mg BID (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-68)		Apremilast 30mg BID (Weeks 0-68)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		4/85 (4.7%)		0/85 (0%)		11/121 (9.1%)		2/120 (1.7%)
Cardiac disorders
Cardiac failure congestive	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Coronary artery stenosis	0/84 (0%)		1/85 (1.2%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Gastrointestinal disorders
Periodontitis	0/84 (0%)		0/85 (0%)		0/85 (0%)		0/121 (0%)		1/120 (0.8%)
Hepatobiliary disorders
Bile duct stone	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Cholelithiasis	0/84 (0%)		1/85 (1.2%)		0/85 (0%)		2/121 (1.7%)		0/120 (0%)
Infections and infestations
Arthritis bacterial	0/84 (0%)		1/85 (1.2%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Pneumonia	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Investigations
Intraocular pressure increased	0/84 (0%)		0/85 (0%)		0/85 (0%)		0/121 (0%)		1/120 (0.8%)
Metabolism and nutrition disorders
Diabetes mellitus	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Colon cancer metastatic	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Lung cancer metastatic	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Nervous system disorders
Cerebral haemorrhage	0/84 (0%)		1/85 (1.2%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Renal and urinary disorders
Renal infarct	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/84 (0%)		0/85 (0%)		0/85 (0%)		1/121 (0.8%)		0/120 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-16)		Apremilast 30mg BID (Weeks 0-16)		Apremilast 20mg BID (Weeks 0-68)		Apremilast 30mg BID (Weeks 0-68)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/84 (10.7%)		16/85 (18.8%)		18/85 (21.2%)		35/121 (28.9%)		40/120 (33.3%)
Gastrointestinal disorders
Abdominal discomfort	1/84 (1.2%)		1/85 (1.2%)		6/85 (7.1%)		3/121 (2.5%)		8/120 (6.7%)
Diarrhoea	1/84 (1.2%)		7/85 (8.2%)		8/85 (9.4%)		10/121 (8.3%)		12/120 (10%)
Infections and infestations
Nasopharyngitis	7/84 (8.3%)		10/85 (11.8%)		10/85 (11.8%)		28/121 (23.1%)		35/120 (29.2%)

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 12 months 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.