Trial Outcomes & Findings for Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis (NCT NCT02289417)

Last Updated: 2020-05-07

Results Overview

Clinical remission was defined as a total Mayo score ≤ 2 points, with no individual subscore exceeding 1 point. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore (RBS) * Endoscopy Subscore * Physician's Global Assessment (PGA). Two-sided 95% confidence intervals (CI) for the within-group percentages are based on the Wilson score method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

170 participants

Primary outcome timeframe

Week 12

Results posted on

2020-05-07

Participant Flow

The study was conducted at 61 sites in Australia (3 sites) and New Zealand (1 site); Bulgaria (6 sites), Czech Republic (2 sites), Hungary (3 sites), Poland (9 sites), Russia (1 site), and Ukraine (10 sites); Canada (2 sites) and United States (13 sites); and France (4 sites), Germany (1 site), Italy (4 sites), and the Netherlands (2 sites).

A total of 170 participants were randomized in a 1:1:1 ratio and received apremilast (30 mg BID or 40 mg BID), or identically appearing placebo and stratified based on concomitant use of oral corticosteroids and previous exposure to immunosuppressants.

Participant milestones

Participant milestones
Measure	Placebo Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the total Mayo score (TMS) continued to receive 30 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Apremilast 40 mg Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Placebo/Apremilast 30 mg Participants initially randomized to placebo capsules in the placebo-controlled period were re-randomized at week 12 to receive 30 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Placebo/Apremilast 40 mg Participants initially randomized to placebo in the placebo-controlled period were re-randomized at week 12 to receive 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Apremilast 30 mg/Apremilast 40 mg Participants initially randomized to 30 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS were re-assigned to 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Apremilast 40 mg/ Apremilast 40 mg Participants initially randomized to 40 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Extension Phase: Apremilast 30 mg Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 30 mg apremilast BID for an additional 52 weeks. This includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4.	Extension Phase Apremilast 40 mg Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4 participants were switched to 30 mg apremilast BID for the remainder of the extension phase.
Placebo-Controlled Phase Weeks 0-12 STARTED	58	57	55	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-12 COMPLETED	51	53	52	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-12 NOT COMPLETED	7	4	3	0	0	0	0	0	0
Active Treatment Phase Weeks 12-52 STARTED	0	41	42	26	25	12	7	0	0
Active Treatment Phase Weeks 12-52 COMPLETED	0	39	32	17	20	7	5	0	0
Active Treatment Phase Weeks 12-52 NOT COMPLETED	0	2	10	9	5	5	2	0	0
Extension Phase Weeks 52-104 STARTED	0	0	0	0	0	0	0	45	54
Extension Phase Weeks 52-104 COMPLETED	0	0	0	0	0	0	0	38	48
Extension Phase Weeks 52-104 NOT COMPLETED	0	0	0	0	0	0	0	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the total Mayo score (TMS) continued to receive 30 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Apremilast 40 mg Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase. At week 12, participants who achieved at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Placebo/Apremilast 30 mg Participants initially randomized to placebo capsules in the placebo-controlled period were re-randomized at week 12 to receive 30 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Placebo/Apremilast 40 mg Participants initially randomized to placebo in the placebo-controlled period were re-randomized at week 12 to receive 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Apremilast 30 mg/Apremilast 40 mg Participants initially randomized to 30 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS were re-assigned to 40 mg apremilast capsules BID for 40 weeks during the active treatment phase.	Apremilast 40 mg/ Apremilast 40 mg Participants initially randomized to 40 mg apremilast capsules BID in the placebo-controlled phase who did not achieve at least a 20% decrease from baseline in the TMS continued to receive 40 mg apremilast capsules BID for an additional 40 weeks during the active treatment phase.	Extension Phase: Apremilast 30 mg Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 30 mg apremilast BID for an additional 52 weeks. This includes participants assigned to 30 mg apremilast BID at week 12, and participants who entered the extension phase after implementation of Protocol Amendment 4.	Extension Phase Apremilast 40 mg Participants who completed 52 weeks of treatment and had a Mayo endoscopy score ≤ 1 at week 52 were eligible to participate in the 52-week extension phase and receive 40 mg apremilast BID for an additional 52 weeks. After implementation of Protocol Amendment 4 participants were switched to 30 mg apremilast BID for the remainder of the extension phase.
Placebo-Controlled Phase Weeks 0-12 Adverse Event	3	0	1	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-12 Withdrawal by Subject	1	3	2	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-12 Lost to Follow-up	0	1	0	0	0	0	0	0	0
Placebo-Controlled Phase Weeks 0-12 Lack of Efficacy	3	0	0	0	0	0	0	0	0
Active Treatment Phase Weeks 12-52 Adverse Event	0	1	4	2	2	1	0	0	0
Active Treatment Phase Weeks 12-52 Pregnancy	0	0	1	0	0	0	0	0	0
Active Treatment Phase Weeks 12-52 Lack of Efficacy	0	1	4	6	2	3	0	0	0
Active Treatment Phase Weeks 12-52 Withdrawal by Subject	0	0	1	0	1	1	0	0	0
Active Treatment Phase Weeks 12-52 Lost to Follow-up	0	0	0	0	0	0	1	0	0
Active Treatment Phase Weeks 12-52 Miscellaneous	0	0	0	1	0	0	1	0	0
Extension Phase Weeks 52-104 Adverse Event	0	0	0	0	0	0	0	2	3
Extension Phase Weeks 52-104 Lack of Efficacy	0	0	0	0	0	0	0	2	2
Extension Phase Weeks 52-104 Withdrawal by Subject	0	0	0	0	0	0	0	2	1
Extension Phase Weeks 52-104 Miscellaneous	0	0	0	0	0	0	0	1	0

Baseline Characteristics

Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Total n=170 Participants Total of all reporting groups
Age, Continuous	42.9 Years STANDARD_DEVIATION 14.04 • n=5 Participants	40.1 Years STANDARD_DEVIATION 13.50 • n=7 Participants	43.4 Years STANDARD_DEVIATION 14.92 • n=5 Participants	42.1 Years STANDARD_DEVIATION 14.15 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	64 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	39 Participants n=7 Participants	34 Participants n=5 Participants	106 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=5 Participants	54 Participants n=7 Participants	46 Participants n=5 Participants	155 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	54 Participants n=5 Participants	52 Participants n=7 Participants	45 Participants n=5 Participants	151 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported or Collected	3 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants
Duration of Ulcerative Colitis	6.85 Years STANDARD_DEVIATION 7.043 • n=5 Participants	6.15 Years STANDARD_DEVIATION 5.432 • n=7 Participants	8.63 Years STANDARD_DEVIATION 10.278 • n=5 Participants	7.19 Years STANDARD_DEVIATION 7.832 • n=4 Participants
Baseline Total Mayo Score (TMS)	8.2 units on a scale STANDARD_DEVIATION 1.68 • n=5 Participants	8.5 units on a scale STANDARD_DEVIATION 1.62 • n=7 Participants	8.1 units on a scale STANDARD_DEVIATION 1.67 • n=5 Participants	8.3 units on a scale STANDARD_DEVIATION 1.65 • n=4 Participants
Modified Mayo Score (MMS)	6.1 units on a scale STANDARD_DEVIATION 1.51 • n=5 Participants	6.4 units on a scale STANDARD_DEVIATION 1.48 • n=7 Participants	6.0 units on a scale STANDARD_DEVIATION 1.47 • n=5 Participants	6.2 units on a scale STANDARD_DEVIATION 1.49 • n=4 Participants
Partial Mayo Score (PMS)	5.6 units on a scale STANDARD_DEVIATION 1.46 • n=5 Participants	5.8 units on a scale STANDARD_DEVIATION 1.44 • n=7 Participants	5.5 units on a scale STANDARD_DEVIATION 1.57 • n=5 Participants	5.6 units on a scale STANDARD_DEVIATION 1.49 • n=4 Participants
Mayo Endoscopic Subscore (MES)	2.6 units on a scale STANDARD_DEVIATION 0.49 • n=5 Participants	2.7 units on a scale STANDARD_DEVIATION 0.45 • n=7 Participants	2.6 units on a scale STANDARD_DEVIATION 0.49 • n=5 Participants	2.6 units on a scale STANDARD_DEVIATION 0.48 • n=4 Participants
Baseline Use of Oral Corticosteroids	17 Participants n=5 Participants	14 Participants n=7 Participants	12 Participants n=5 Participants	43 Participants n=4 Participants
Previous Exposure to Use of Immunosuppressants	17 Participants n=5 Participants	18 Participants n=7 Participants	16 Participants n=5 Participants	51 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The intent to treat (ITT) population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved a Clinical Remission by Total Mayo Score (TMS) at Week 12	12.1 Percentage of Participants Interval 6.0 to 22.9	31.6 Percentage of Participants Interval 21.0 to 44.5	21.8 Percentage of Participants Interval 12.9 to 34.4

SECONDARY outcome

Timeframe: Week 12

Clinical response was defined as a decrease from baseline in the TMS of at least 3 points and at least 30%, along with a reduction in the rectal bleeding subscore (RBS) of at least 1 point or an absolute RBS of ≤ 1. The TMS is an instrument designed to measure disease activity of UC. The Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. * Stool Frequency Subscore (SFS) * Rectal Bleeding Subscore * Endoscopy Subscore * Physician's Global Assessment (PGA) Rectal bleeding (subscore 0-3) was defined as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool 3. = Blood alone passes Two-sided 95% CI for the within-group percentages are based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved a Clinical Response by Total Mayo Score and the Reduction in the Rectal Bleeding Subscore at Week 12	46.6 Percentage of Participants Interval 34.3 to 59.2	61.4 Percentage of Participants Interval 48.4 to 72.9	67.3 Percentage of Participants Interval 54.1 to 78.2

SECONDARY outcome

Timeframe: Week 12

Population: The intent to treat population included all participants who received at least one dose of IP. Participants with insufficient data for response determination were considered non-responders.

An endoscopic remission was defined as a Mayo endoscopic subscore (MES) of 0 at Week 12. The MES subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3. = Severe Disease (spontaneous bleeding, ulceration) The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved an Endoscopic Remission at Week 12	3.4 Percentage of Participants Interval 1.0 to 11.7	8.8 Percentage of Participants Interval 3.8 to 18.9	7.3 Percentage of Participants Interval 2.9 to 17.3

SECONDARY outcome

Timeframe: Week 12

An endoscopic response is defined as a decrease from baseline of at least 1 point in the MES at Week 12. The Mayo endoscopy subscore findings were defined as: 0 = Normal or inactive disease 1. = Mild Disease (erythema, decreased vascular pattern, mild friability) 2. = Moderate Disease (marked erythema, lack of vascular pattern, friability erosions) 3 = Severe Disease (spontaneous bleeding, ulceration). The endoscopy subscores consisted of findings that were centrally read through proctosigmoidoscopy, graded from 0 to 3 with higher scores indicating more severe disease. Two-sided 95% CIs for the within-group percentage were based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved an Endoscopic Response at Week 12	41.4 Percentage of Participants Interval 29.6 to 54.2	73.7 Percentage of Participants Interval 61.0 to 83.4	47.3 Percentage of Participants Interval 34.7 to 60.2

SECONDARY outcome

Timeframe: Week 12

The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved a Rectal Bleeding Subscore (RBS) of ≤ 1 at Week 12	72.4 Percentage of Participants Interval 59.8 to 82.2	84.2 Percentage of Participants Interval 72.6 to 91.5	87.3 Percentage of Participants Interval 76.0 to 93.7

SECONDARY outcome

Timeframe: Week 12

Clinical remission was defined as a modified Mayo score of ≤ 2, with no individual subscore \> 1, at Week 12. The MMS was based on a modification of the total Mayo score (TMS) which included the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the Physician's Global Assessment (PGA) subscore, since this was a global measure that is subjective in nature. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved Clinical Remission in the Modified Mayo Subscore (MMS) at Week 12	19.0 Percentage of Participants Interval 10.9 to 30.9	43.9 Percentage of Participants Interval 31.8 to 56.7	27.3 Percentage of Participants Interval 17.3 to 40.2

SECONDARY outcome

Timeframe: Week 12

Clinical response in the MMS was defined as a decrease from baseline in the MMS of at least 2 points and at least 25%, along with a reduction in the RBS of at least 1 point or an absolute RBS ≤ 1. The MMS was based on the stool frequency, rectal bleeding, and endoscopic subscores of the TMS and excluded the PGA subscore. The MMS ranges from 0 to 9 points with higher scores indicating greater disease severity. The RBS was measured as: 0 = No blood seen 1. = Streaks of blood with stool less than half the time 2. = Obvious blood with stool most of the time 3. = Blood alone passes The daily bleeding score represents the most severe bleeding of the day. The endoscopy subscores was centrally reviewed. Two-sided confidence intervals for the within-group percentage were based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved Clinical Response in the Modified Mayo Subscore (MMS) at Week 12	46.6 Percentage of Participants Interval 34.3 to 59.2	63.2 Percentage of Participants Interval 50.2 to 74.5	67.3 Percentage of Participants Interval 54.1 to 78.2

SECONDARY outcome

Timeframe: Week 8

Clinical remission in the partial Mayo subscore was defined as a PMS of 2 points or lower, with no individual subscore \>1. The PMS is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved Clinical Remission in the Partial Mayo Subscore (PMS) With no Individual Subscore >1 at Week 8	32.8 Percentage of Participants Interval 22.1 to 45.6	47.4 Percentage of Participants Interval 35.0 to 60.1	52.7 Percentage of Participants Interval 39.8 to 65.3

SECONDARY outcome

Timeframe: Week 8

Clinical response in the PMS was defined as a decrease from baseline in PMS of at least 2 points and at least 25%, with an accompanying decrease in the RBS of at least 1 point or an absolute RBS of 0 or 1. The PMS score is a discrete ordinal scale ranging from 0 (normal or inactive disease) to 9 (severe disease) and is a composite of 3 subscores: Stool Frequency Subscore, Rectal Bleeding Subscore, and Physician's Global Assessment Subscore, each of which ranges from 0 (normal) to 3 (severe disease). Two-sided 95% CI for the within-group proportions are based on the Wilson score method.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
Percentage of Participants Who Achieved Clinical Response in the Partial Mayo Subscore at Week 8	48.3 Percentage of Participants Interval 35.9 to 60.8	64.9 Percentage of Participants Interval 51.9 to 76.0	81.8 Percentage of Participants Interval 69.7 to 89.8

SECONDARY outcome

Timeframe: From the first dose of investigational product (IP) and no later than 28 days after the last dose of IP for those who had completed the study or discontinued (D/C) early; maximum duration of exposure to treatment was 12.00 weeks

Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product.

A TEAE was defined as any adverse event (AE) occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Serious IP-related TEAE	0 Participants	0 Participants	0 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE Leading to IP Withdrawal	5 Participants	0 Participants	1 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE	31 Participants	28 Participants	36 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any IP-related TEAE	12 Participants	13 Participants	20 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Severe TEAE	4 Participants	0 Participants	1 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any Serious TEAE	2 Participants	0 Participants	1 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE Leading to IP Interruption	1 Participants	0 Participants	0 Participants
The Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase Any TEAE Leading to Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early; median duration of exposure to treatment was 12.00 weeks

Population: Safety population included all participants who were enrolled and received at least 1 dose of investigational product.

A TEAE was defined as any AE occurring or worsening on or after the first treatment of apremilast and up to 28 days after the last apremilast dose or the last follow-up date, whichever occurred earlier. A serious AE = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was assessed by the investigator and based on the following scale: Mild = asymptomatic or mild symptoms; clinical or diagnostic observations only; Moderate = Symptoms cause moderate discomfort; Severe (could be non-serious or serious) = symptoms causing severe discomfort/pain.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=57 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=55 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
The Number of Participants Who Discontinued Apremilast Due to Treatment Emergent Adverse Events During the Placebo-Controlled Period	5 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From first dose of IP and no later than 28 days after last dose of IP for those who completed the active treatment phase or D/C early; median duration of exposure = 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms

Population: Apremilast exposure population included all participants who were randomized at Week 0 or assigned at Week 12 to an apremilast group and received at least 1 dose of apremilast.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=80 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg n=11 Participants Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any TEAE	60 Participants	67 Participants	8 Participants
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any Severe TEAE	5 Participants	6 Participants	0 Participants
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any Serious TEAE	6 Participants	8 Participants	1 Participants
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any TEAE Leading to Drug Withdrawal	3 Participants	9 Participants	1 Participants
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any TEAE Leading to Drug Interruption	1 Participants	4 Participants	0 Participants
The Number of Participants Who Experienced TEAEs During the Apremilast (APR) Exposure Period (Active Treatment Phase) Through Week 52 Any TEAE Leading to Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From the first dose of IP at Week 52 and no later than 28 days after the last dose of IP for those who completed the study or had discontinued early; median exposure of apremilast for the total apremilast group was 52 weeks.

Population: Participants who received at least 1 dose of apremilast after week 52.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants were randomized to identically matching placebo capsules and received placebo capsules by mouth (PO) twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg n=54 Participants Participants were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg Participants were randomized to 40 mg apremilast capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any Serious IP-related TEAE	0 Participants	1 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any TEAE	16 Participants	27 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any Severe TEAE	1 Participants	0 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any Serious TEAE	4 Participants	3 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any TEAE Leading to IP Withdrawal	2 Participants	1 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any TEAE Leading to IP Interruption	1 Participants	0 Participants	—
The Number of Participants Who Experienced TEAEs During Week 52 to Week 104 (Extension Phase) Any TEAE Leading to Death	0 Participants	0 Participants	—

Adverse Events

Placebo (Placebo Controlled Period)

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Apremilast 30 mg (Placebo Controlled Period)

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Apremilast 40 mg BID (Placebo Controlled Period)

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Apremilast 30 mg (Apremilast Exposure Period)

Serious events: 9 serious events

Other events: 49 other events

Deaths: 0 deaths

Apremilast 40 mg (Apremilast Exposure Period)

Serious events: 11 serious events

Other events: 53 other events

Deaths: 0 deaths

Apremilast 30/40 mg (Apremilast Exposure Period)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Placebo Controlled Period) n=58 participants at risk TEAEs for participants who were randomized to identically matching placebo capsules twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg (Placebo Controlled Period) n=57 participants at risk TEAEs for participants who were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg BID (Placebo Controlled Period) n=55 participants at risk TEAEs for participants who were randomized to apremilast 40 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg (Apremilast Exposure Period) n=83 participants at risk TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12.	Apremilast 40 mg (Apremilast Exposure Period) n=80 participants at risk TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12.	Apremilast 30/40 mg (Apremilast Exposure Period) n=11 participants at risk TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12. for participants who initially received 30 mg apremilast dosage and switched to 40 mg apremilast capsules BID at Week 12.
Gastrointestinal disorders Colitis ulcerative	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Cardiac disorders Acute myocardial infarction	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Abdominal hernia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Crohn's disease	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Diarrhoea	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Inguinal hernia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Pancreatitis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Hepatobiliary disorders Cholecystitis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Clostridium difficile infection	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Epididymitis tuberculous	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Pilonidal cyst	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Rectal abscess	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Urinary tract infection	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Epididymal neoplasm	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Renal and urinary disorders Nephrolithiasis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Renal and urinary disorders Renal colic	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Reproductive system and breast disorders Menorrhagia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.

Other adverse events

Other adverse events
Measure	Placebo (Placebo Controlled Period) n=58 participants at risk TEAEs for participants who were randomized to identically matching placebo capsules twice a day (BID) for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg (Placebo Controlled Period) n=57 participants at risk TEAEs for participants who were randomized to apremilast 30 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 40 mg BID (Placebo Controlled Period) n=55 participants at risk TEAEs for participants who were randomized to apremilast 40 mg capsules PO BID for 12 weeks during the double-blind placebo-controlled phase.	Apremilast 30 mg (Apremilast Exposure Period) n=83 participants at risk TEAEs during the apremilast 30 mg BID treatment for participants who received 30 mg apremilast capsules BID only and participants who initially received 30 mg apremilast capsules BID and switched to 40 mg apremilast capsules BID at Week 12, and participants who initially received placebo capsules BID and switched to 30 mg apremilast capsules BID at Week 12.	Apremilast 40 mg (Apremilast Exposure Period) n=80 participants at risk TEAEs during the apremilast 40 mg BID treatment for participants who received 40 mg apremilast capsules BID only, and participants who initially received placebo BID and switched to 40 mg apremilast capsules BID at Week 12.	Apremilast 30/40 mg (Apremilast Exposure Period) n=11 participants at risk TEAEs during the apremilast 40 mg BID treatment for participants who initially received 30 mg apremilast BID and switched to apremilast 40 mg BID at Week 12. for participants who initially received 30 mg apremilast dosage and switched to 40 mg apremilast capsules BID at Week 12.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	6.2% 5/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Blood and lymphatic system disorders Anaemia	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	4.8% 4/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.0% 4/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Dyspepsia	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Nausea	8.6% 5/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.3% 3/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	10.9% 6/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.6% 8/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	11.2% 9/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	27.3% 3/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
General disorders Asthenia	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.3% 3/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	6.0% 5/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	18.2% 2/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Upper respiratory tract infection	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	4.8% 4/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.0% 4/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Metabolism and nutrition disorders Decreased appetite	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.5% 2/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Abdominal pain	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.3% 3/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	4.8% 4/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Anorectal discomfort	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Colitis ulcerative	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	7.5% 6/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Diarrhoea	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	6.0% 5/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	7.5% 6/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	18.2% 2/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Gastritis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.0% 4/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Inguinal hernia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Swollen tongue	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Gastrointestinal disorders Vomiting	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.5% 2/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.6% 2/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.6% 3/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	27.3% 3/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
General disorders Influenza like illness	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
General disorders Pyrexia	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	18.2% 2/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Gastroenteritis	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.6% 3/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Influenza	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Nasopharyngitis	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	7.0% 4/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.6% 2/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	8.4% 7/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	10.0% 8/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	18.2% 2/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Periodontitis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Pneumonia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Infections and infestations Sinusitis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	4.8% 4/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Investigations Blood lactate dehydrogenase increased	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Investigations Faecal calprotectin increased	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Musculoskeletal and connective tissue disorders Arthralgia	3.4% 2/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	6.0% 5/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	7.5% 6/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Musculoskeletal and connective tissue disorders Back pain	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.5% 3/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiomyolipoma	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Nervous system disorders Headache	6.9% 4/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	21.1% 12/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	25.5% 14/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	20.5% 17/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	31.2% 25/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	18.2% 2/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Nervous system disorders Migraine	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.8% 3/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Nervous system disorders Sciatica	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Nervous system disorders Sinus headache	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Psychiatric disorders Depressed mood	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.4% 2/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	5.0% 4/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Psychiatric disorders Depression	1.7% 1/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Psychiatric disorders Insomnia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.5% 2/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	3.6% 3/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Renal and urinary disorders Haematuria	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	2.5% 2/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Skin and subcutaneous tissue disorders Rash	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.
Vascular disorders Angiopathy	0.00% 0/58 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.8% 1/57 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/55 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	1.2% 1/83 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	0.00% 0/80 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.	9.1% 1/11 • From the first dose of IP and no later than 28 days after the last dose of IP for those who had completed the study or discontinued early. AEs are reported for the placebo-controlled phase from Week 0 to Week 12 and for the apremilast exposure period from Week 0 to Week 104. Median duration of study drug was 12 weeks in the placebo controlled phase, 41.00, 44.15 and 40.00 weeks respectively for 30 mg, 40 mg and 30 mg/40 mg APR arms in the active treatment phase and 52 weeks in the extension phase. MedDRA Version 20.1 was utilized in the placebo controlled phase and Version 22 in the active treatment and extension phase.

Additional Information

Anne McClain, Senior Manager, Clinical Trial Disclosure

Celgene Corporation

Phone: 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 \> 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 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
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