Trial Outcomes & Findings for Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis (NCT NCT01194219)

NCT ID: NCT01194219

Last Updated: 2022-03-15

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

844 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2022-03-15

Participant Flow

The study was conducted at 76 study centers in 8 countries

Participant milestones

Participant milestones
Measure	Apremilast Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)	Apremilast-Apremilast Participants who were initially randomized to APR 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16) remained on APR 30 mg BID during the Maintenance Phase (Weeks 16-32).	Placebo-Apremilast Participants who were initially randomized to identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32)	APR-APR-Re-randomized to PBO Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders \[ie, having a ≥ Psoriasis Area and Severity Index score of 75 (PASI-75) response\] were re-randomized to PBO during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who retained their ≥PASI-75 response through the Randomized Withdrawal Phase remained on PBO until week 52. Those participants who lost their PASI-75 improvement achieved at week 32, were switched back to APR 30 mg BID at the time loss of effect was observed. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260, and received APR 30 mg BID for the remainder of their participation.	APR-APR-Re-randomized to APR Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders (ie, having a ≥PASI-75 response) were re-randomized to APR 30 mg BID during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	APR-APR-APR + Optional Topicals/UVB Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) and non-responders (ie, having a response of \<PASI-50), remained on APR 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. Those participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	PBO-APR-APR + Optional Topicals/ UVB Participants who were initially randomized to placebo BID during the 16-week Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to APR 30 mg BID and continued dosing with APR 30 mg BID during the Maintenance Phase (Weeks 16-32). At week 32, all participants continued to receive APR 30mg BID. Those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) or non-responders (ie, having a response of \< PASI-50) were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these partial or non-responders received additional topical or phototherapy. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Apremilast (Long-term Extension) Participants who were initially randomized to APR 30 mg BID during the 16-week placebo-controlled phase (Weeks 0-16) continued receiving APR 30 mg BID through the Maintenance Phase (Weeks 16-32) and were re-randomized to APR 30 mg tablets or placebo tablets BID during the Randomized Withdrawal Phase; participants were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and received APR 30 mg BID for the remainder of their participation.	Placebo-Apremilast (Long-term Extension) Participants who were initially randomized to identically matching placebo BID during the placebo-controlled phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32) and Randomized Withdrawal Phase were eligible to participate in the Long-term Extension phase from Weeks 52-260 and continued on apremilast 30 mg tablets BID for the remainder of their participation.
Placebo-Controlled Phase Weeks 0-16 STARTED	562	282	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Received Apremilast	560	282	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 COMPLETED	503	249	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 NOT COMPLETED	59	33	0	0	0	0	0	0	0	0
Maintenance Phase Weeks16-32 STARTED	0	0	494	245	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Received Apremilast	0	0	493	244	0	0	0	0	0	0
Maintenance Phase Weeks16-32 COMPLETED	0	0	424	215	0	0	0	0	0	0
Maintenance Phase Weeks16-32 NOT COMPLETED	0	0	70	30	0	0	0	0	0	0
Randomized Withdrawal Phase-Weeks 32-52 STARTED	0	0	0	0	77	77	245	208	0	0
Randomized Withdrawal Phase-Weeks 32-52 Received Topical + Light Therapy	0	0	0	0	0	0	126	91	0	0
Randomized Withdrawal Phase-Weeks 32-52 COMPLETED	0	0	0	0	73	73	184	163	0	0
Randomized Withdrawal Phase-Weeks 32-52 NOT COMPLETED	0	0	0	0	4	4	61	45	0	0
Long-Term Extension Weeks 52 to 260 STARTED	0	0	0	0	0	0	0	0	306	153
Long-Term Extension Weeks 52 to 260 Received at Least 1 Dose of IP	0	0	0	0	0	0	0	0	304	153
Long-Term Extension Weeks 52 to 260 COMPLETED	0	0	0	0	0	0	0	0	86	41
Long-Term Extension Weeks 52 to 260 NOT COMPLETED	0	0	0	0	0	0	0	0	220	112

Reasons for withdrawal

Reasons for withdrawal
Measure	Apremilast Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)	Apremilast-Apremilast Participants who were initially randomized to APR 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16) remained on APR 30 mg BID during the Maintenance Phase (Weeks 16-32).	Placebo-Apremilast Participants who were initially randomized to identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32)	APR-APR-Re-randomized to PBO Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders \[ie, having a ≥ Psoriasis Area and Severity Index score of 75 (PASI-75) response\] were re-randomized to PBO during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who retained their ≥PASI-75 response through the Randomized Withdrawal Phase remained on PBO until week 52. Those participants who lost their PASI-75 improvement achieved at week 32, were switched back to APR 30 mg BID at the time loss of effect was observed. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260, and received APR 30 mg BID for the remainder of their participation.	APR-APR-Re-randomized to APR Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered responders (ie, having a ≥PASI-75 response) were re-randomized to APR 30 mg BID during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	APR-APR-APR + Optional Topicals/UVB Participants who were initially randomized to APR 30 mg BID during the 16-week Placebo-controlled Phase (Weeks 0-16) continued dosing with APR 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) and non-responders (ie, having a response of \<PASI-50), remained on APR 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. Those participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	PBO-APR-APR + Optional Topicals/ UVB Participants who were initially randomized to placebo BID during the 16-week Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to APR 30 mg BID and continued dosing with APR 30 mg BID during the Maintenance Phase (Weeks 16-32). At week 32, all participants continued to receive APR 30mg BID. Those participants who were considered partial responders (ie, having a response of PASI-50 to PASI-74) or non-responders (ie, having a response of \< PASI-50) were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these partial or non-responders received additional topical or phototherapy. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.	Apremilast (Long-term Extension) Participants who were initially randomized to APR 30 mg BID during the 16-week placebo-controlled phase (Weeks 0-16) continued receiving APR 30 mg BID through the Maintenance Phase (Weeks 16-32) and were re-randomized to APR 30 mg tablets or placebo tablets BID during the Randomized Withdrawal Phase; participants were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and received APR 30 mg BID for the remainder of their participation.	Placebo-Apremilast (Long-term Extension) Participants who were initially randomized to identically matching placebo BID during the placebo-controlled phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg tablets BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32) and Randomized Withdrawal Phase were eligible to participate in the Long-term Extension phase from Weeks 52-260 and continued on apremilast 30 mg tablets BID for the remainder of their participation.
Placebo-Controlled Phase Weeks 0-16 Adverse Event	23	5	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Lack of Efficacy	2	7	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Noncompliance with study drug	7	0	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Withdrawal by Subject	12	9	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Death	0	1	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Lost to Follow-up	7	9	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Protocol Violation	7	1	0	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-16 Miscellaneous	1	1	0	0	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Adverse Event	0	0	8	9	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Lack of Efficacy	0	0	37	15	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Non-compliance with Study Drug	0	0	2	1	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Withdrawal by Subject	0	0	12	3	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Lost to Follow-up	0	0	9	0	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Protocol Violation	0	0	0	1	0	0	0	0	0	0
Maintenance Phase Weeks16-32 Other	0	0	2	1	0	0	0	0	0	0
Randomized Withdrawal Phase-Weeks 32-52 Adverse Event	0	0	0	0	0	1	6	5	0	0
Randomized Withdrawal Phase-Weeks 32-52 Lack of Efficacy	0	0	0	0	1	1	35	33	0	0
Randomized Withdrawal Phase-Weeks 32-52 Non-compliance with Study Drug	0	0	0	0	1	0	2	0	0	0
Randomized Withdrawal Phase-Weeks 32-52 Withdrawal by Subject	0	0	0	0	1	0	12	6	0	0
Randomized Withdrawal Phase-Weeks 32-52 Lost to Follow-up	0	0	0	0	1	2	5	0	0	0
Randomized Withdrawal Phase-Weeks 32-52 Protocol Violation	0	0	0	0	0	0	0	1	0	0
Randomized Withdrawal Phase-Weeks 32-52 Other	0	0	0	0	0	0	1	0	0	0
Long-Term Extension Weeks 52 to 260 Adverse Event	0	0	0	0	0	0	0	0	25	14
Long-Term Extension Weeks 52 to 260 Lack of Efficacy	0	0	0	0	0	0	0	0	81	49
Long-Term Extension Weeks 52 to 260 Noncompliance with IP	0	0	0	0	0	0	0	0	9	4
Long-Term Extension Weeks 52 to 260 Withdrawal by Subject	0	0	0	0	0	0	0	0	66	32
Long-Term Extension Weeks 52 to 260 Death	0	0	0	0	0	0	0	0	1	1
Long-Term Extension Weeks 52 to 260 Lost to Follow-up	0	0	0	0	0	0	0	0	24	10
Long-Term Extension Weeks 52 to 260 Protocol Violation	0	0	0	0	0	0	0	0	3	0
Long-Term Extension Weeks 52 to 260 Miscellaneous	0	0	0	0	0	0	0	0	11	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apremilast n=562 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)	Total n=844 Participants Total of all reporting groups
Age, Continuous	45.8 years STANDARD_DEVIATION 13.07 • n=5 Participants	46.5 years STANDARD_DEVIATION 12.72 • n=7 Participants	46.0 years STANDARD_DEVIATION 12.95 • n=5 Participants
Sex: Female, Male Female	183 Participants n=5 Participants	88 Participants n=7 Participants	271 Participants n=5 Participants
Sex: Female, Male Male	379 Participants n=5 Participants	194 Participants n=7 Participants	573 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=5 Participants	5 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Asian	28 participants n=5 Participants	16 participants n=7 Participants	44 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	18 participants n=5 Participants	10 participants n=7 Participants	28 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized White	507 participants n=5 Participants	250 participants n=7 Participants	757 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Duration of Plaque Psoriasis <10 years	150 years n=5 Participants	85 years n=7 Participants	235 years n=5 Participants
Duration of Plaque Psoriasis 10 to < 20 years	159 years n=5 Participants	73 years n=7 Participants	232 years n=5 Participants
Duration of Plaque Psoriasis ≥ 20 years	253 years n=5 Participants	122 years n=7 Participants	375 years n=5 Participants
Duration of Plaque Psoriasis Missing	0 years n=5 Participants	2 years n=7 Participants	2 years n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=562 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline	33.1 percentage of participants	5.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=562 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With At Least 2 Points Reduction From Baseline	21.7 percentage of participants	3.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

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

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=559 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=278 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percent Change From Baseline in Percent of Affected Body Surface Area (BSA) at Week 16	-47.77 percent change Standard Error 1.634 • Interval -44.56 to -50.98	-6.99 percent change Standard Error 2.317 • Interval -2.54 to -11.54

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=559 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=278 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16	-52.1 percent change Standard Error 1.37	-16.8 percent change Standard Error 1.94

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=562 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline	58.7 Percentage of Participants	17.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline and Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=559 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=277 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Change From Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16	-31.5 units on a scale Standard Error 1.30	-7.3 units on a scale Standard Error 1.85

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=556 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=274 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16	-6.6 units on a scale Standard Error 0.27	-2.1 units on a scale Standard Error 0.38

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=556 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=273 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Change From Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16	2.28 units on a scale Standard Error 0.371	-0.81 units on a scale Standard Error 0.529

SECONDARY outcome

Timeframe: Baseline to Week 16

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=562 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline	20.3 percentage of participants	3.5 percentage of participants

SECONDARY outcome

Timeframe: Week 32 to Week 52

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

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=77 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=77 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Kaplan Meier Estimate of Time to Loss of PASI-75 Response (Loss of Effect) at Week 32 During the Re-Randomized Treatment Withdrawal Phase	17.7 Weeks Interval 13.0 to The upper limit was not available since there were not enough participants who lost response by the end of the Randomized Withdrawal Phase for the estimation.	5.1 Weeks Interval 4.1 to 8.1

SECONDARY outcome

Timeframe: Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.

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

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.

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=560 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=282 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE	388 participants	157 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Drug-Related TEAE	224 participants	58 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Severe TEAE	20 participants	9 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Serious TEAE	12 participants	8 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Serious Drug-Related TEAE	4 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE leading to Drug Interruption	37 participants	13 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE leading to drug withdrawal	29 participants	9 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE Leading to Death	1 participants	1 participants

SECONDARY outcome

Timeframe: Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks

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

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=804 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any Serious TEAE	74 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any Serious Drug-Related TEAE	12 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any At TEAE	675 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any Drug-Related TEAE	372 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any Severe TEAE	78 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any TEAE Leading to Drug Interruption	107 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any TEAE Leading to Drug withdrawal	98 participants	—
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260 Any TEAE Leading to Death	3 participants	—

SECONDARY outcome

Timeframe: Weeks 0 to Week 16

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

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=282 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) n=560 Participants Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase PASI ≥ 125% of Baseline score after last dose [3]	3 participants	3 participants
Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase Participants with any psoriasis flare [1]	7 participants	6 participants
Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase Participants with any psoriasis rebound [2]	1 participants	1 participants

SECONDARY outcome

Timeframe: Week 0 to Week 260

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

Outcome measures

Outcome measures
Measure	Placebo/Apremilast n=804 Participants Participants were initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)	Placebo (PBO) Participants were initially randomized to identically matching placebo (PBO) tablets twice daily BID during the Placebo-controlled Phase (Weeks 0-16)
Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260 Participants with any psoriasis flare [1]	35 participants	—
Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260 Participants with any psoriasis rebound [2]	12 participants	—
Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260 PASI ≥ 125% of Baseline score after last dose [3]	26 participants	—

Adverse Events

Placebo (Placebo-Controlled Phase) Weeks 0-16

Serious events: 8 serious events

Other events: 90 other events

Deaths: 0 deaths

Apremilast (Placebo-Controlled Phase) Weeks 0-16

Serious events: 12 serious events

Other events: 260 other events

Deaths: 0 deaths

APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Apremilast (Apremilast Exposure Period) Weeks 0-260

Serious events: 74 serious events

Other events: 503 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo (Placebo-Controlled Phase) Weeks 0-16 n=282 participants at risk Participants randomized and received identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16)	Apremilast (Placebo-Controlled Phase) Weeks 0-16 n=560 participants at risk Participants randomized and received apremilast 30 mg tablets BID during the Placebo-Controlled Phase (Weeks 0-16)	APR-APR-PBO Randomized Withdrawal Phase Weeks 32-52 n=77 participants at risk Participants re-randomized and received placebo tablets BID at Week 32. Data from Week 32 up to Week 52 when participants received placebo treatment.	Apremilast (Apremilast Exposure Period) Weeks 0-260 n=804 participants at risk Participants who received apremilast 30 mg tablets BID, regardless of when the apremilast exposure started (at Week 0 or at week 16), up until Week 260. Adverse events associated with apremilast treatment up to Week 260 were included. AEs that started more than 28 days after Placebo treatment and prior to resuming apremilast were excluded for participants who were re-randomized to Placebo at Week 32.
Gastrointestinal disorders Diarrhoea	7.1% 20/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	18.8% 105/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	0.00% 0/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	20.3% 163/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Gastrointestinal disorders Nausea	6.7% 19/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	15.7% 88/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	0.00% 0/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	16.2% 130/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Infections and infestations Gastroenteritis	2.1% 6/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	1.8% 10/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	0.00% 0/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	5.1% 41/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Infections and infestations Nasopharyngitis	8.2% 23/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	7.3% 41/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	3.9% 3/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	16.3% 131/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Infections and infestations Sinusitis	1.8% 5/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	2.9% 16/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	1.3% 1/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	5.6% 45/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Infections and infestations Upper respiratory tract infection	7.4% 21/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	10.2% 57/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	2.6% 2/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	22.8% 183/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Musculoskeletal and connective tissue disorders Arthralgia	1.8% 5/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	1.6% 9/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	2.6% 2/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	6.3% 51/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Musculoskeletal and connective tissue disorders Back pain	0.71% 2/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	2.5% 14/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	1.3% 1/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	6.2% 50/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Nervous system disorders Headache	4.6% 13/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	5.5% 31/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	0.00% 0/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	7.7% 62/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Nervous system disorders Tension headache	4.3% 12/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	7.3% 41/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	2.6% 2/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	10.4% 84/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks
Vascular disorders Hypertension	2.5% 7/282 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	1.8% 10/560 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	0.00% 0/77 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks	7.0% 56/804 • AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 15.0 and 14.8, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 8.1 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 97.83 weeks

Additional Information

Anne McClain

Celgene Corporation

Phone: 1-888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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