Trial Outcomes & Findings for Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy (NCT NCT03721172)

NCT ID: NCT03721172

Last Updated: 2024-05-29

Results Overview

The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation. An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 595 participants
• Primary outcome timeframe: Baseline and Week 16 of the placebo-controlled phase
• Results posted on: 2024-05-29

Participant Flow

Participants were enrolled at 61 research centers in the United States and Canada from March 2019 to July 2020.

Participants were randomized in a 1:1 ratio to receive either apremilast or matched placebo for the first 16 weeks (placebo-controlled phase) of the study. At Week 16, eligible participants may have continued on active treatment by entering a 16 week extension phase (apremilast extension phase), total = 32 weeks.

Participant milestones

Measure	Extension Phase: Apremilast 30 mg Eligible participants who completed the placebo-controlled phase entered the extension phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).	Placebo-controlled Phase: Placebo Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
Placebo-controlled Phase STARTED	0	298	297
Placebo-controlled Phase Received at Least 1 Dose of Treatment	0	297	297
Placebo-controlled Phase COMPLETED	0	246	258
Placebo-controlled Phase NOT COMPLETED	0	52	39
Apremilast Extension Phase STARTED	503	0	0
Apremilast Extension Phase Received at Least 1 Dose	503	0	0
Apremilast Extension Phase COMPLETED	437	0	0
Apremilast Extension Phase NOT COMPLETED	66	0	0

Reasons for withdrawal

Measure	Extension Phase: Apremilast 30 mg Eligible participants who completed the placebo-controlled phase entered the extension phase and received apremilast 30 mg as oral tablets BID for up to an additional 16 weeks (Week 16 to Week 32).	Placebo-controlled Phase: Placebo Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).
Placebo-controlled Phase Adverse Event	0	7	7
Placebo-controlled Phase Lack of Efficacy	0	4	0
Placebo-controlled Phase Non-compliance with study drug	0	0	1
Placebo-controlled Phase Lost to Follow-up	0	15	13
Placebo-controlled Phase Withdrawal by Subject	0	23	18
Placebo-controlled Phase Other	0	3	0
Apremilast Extension Phase Adverse Event	10	0	0
Apremilast Extension Phase Lack of Efficacy	2	0	0
Apremilast Extension Phase Non-compliance with study drug	1	0	0
Apremilast Extension Phase Lost to Follow-up	20	0	0
Apremilast Extension Phase Protocol Violation	1	0	0
Apremilast Extension Phase Physician Decision	1	0	0
Apremilast Extension Phase Withdrawal by Subject	21	0	0
Apremilast Extension Phase Other	3	0	0
Apremilast Extension Phase Other (Related to COVID-19)	7	0	0

Baseline Characteristics

Apremilast as a Direct Treatment for Mild-to-moderate Plaque Psoriasis Versus Placebo: an Analysis of Clinical Safety and Efficacy

Baseline characteristics by cohort

Measure	Placebo-controlled Phase: Placebo n=298 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=297 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Total n=595 Participants Total of all reporting groups
Age, Continuous	48.3 years STANDARD_DEVIATION 14.45 • n=5 Participants	49.2 years STANDARD_DEVIATION 14.65 • n=7 Participants	48.7 years STANDARD_DEVIATION 14.55 • n=5 Participants
Sex: Female, Male Female	147 Participants n=5 Participants	123 Participants n=7 Participants	270 Participants n=5 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	174 Participants n=7 Participants	325 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	260 Participants n=5 Participants	264 Participants n=7 Participants	524 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	14 Participants n=7 Participants	31 Participants n=5 Participants
Race (NIH/OMB) White	257 Participants n=5 Participants	254 Participants n=7 Participants	511 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Static Physician Global Assessment (sPGA) Score 2 (mild)	91 Participants n=5 Participants	91 Participants n=7 Participants	182 Participants n=5 Participants
Static Physician Global Assessment (sPGA) Score 3 (moderate)	207 Participants n=5 Participants	206 Participants n=7 Participants	413 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: Intent-to-treat (ITT) analysis set: all participants who were randomized into the placebo controlled phase.

The sPGA is a 5-point scale where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, and 4 =severe. Scores incorporate an assessment by the Investigator of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation.

An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with at least a 2-point reduction from baseline at Week 16.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=298 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=297 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16 During the Placebo-Controlled Phase	4.1 Percentage of participants Interval 1.8 to 6.4	21.6 Percentage of participants Interval 16.7 to 26.4	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set: all participants who were randomized in the placebo-controlled phase.

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=298 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=297 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Percentage of Participants With a ≥ 75 Percent (%) Improvement From Baseline in Affected Body Surface Area (BSA) at Week 16	7.4 Percentage of participants Interval 4.2 to 10.6	33.0 Percentage of participants Interval 27.4 to 38.6	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with a baseline value and at least one post-baseline value at Week 16

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).

A negative change from baseline indicates a reduction of affected BSA.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=249 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=261 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Change From Baseline in Percentage of Affected BSA at Week 16	-0.07 Percentage change of affected BSA Standard Error 0.24	-3.45 Percentage change of affected BSA Standard Error 0.24	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with a baseline value and at least one post-baseline value at Week 16

The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.

PASI scores range from 0 to 72, with higher scores reflecting greater disease severity.

A negative change from baseline indicates an improvement of disease symptoms.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=249 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=261 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Change From Baseline in Total Psoriasis Area Severity Index (PASI) Score at Week 16	-0.54 Scores on a scale Standard Error 0.20	-3.47 Scores on a scale Standard Error 0.20	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with baseline BSA \> 3%.

The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total body surface area).

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=255 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=245 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Percentage of Participants Who Achieved BSA ≤ 3% for Participants With Baseline Affected BSA > 3% at Week 16	22.9 Percentage of participants Interval 17.4 to 28.4	61.0 Percentage of participants Interval 54.6 to 67.3	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with baseline whole body itch NRS score ≥ 4.

The whole body itch NRS is a self-reported measure where participants were asked to assess whole body itch and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A reduction in score from baseline represents an improvement in symptoms.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=249 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=253 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Percentage of Participants With ≥ 4-point Reduction From Baseline in Whole Body Itch Numeric Rating Scale (NRS) Score at Week 16 Who Had Baseline Whole Body Itch NRS ≥ 4	18.6 Percentage of participants Interval 13.4 to 23.7	43.2 Percentage of participants Interval 36.9 to 49.5	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with baseline ScPGA Score ≥ 2).

The ScPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an Investigator's assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation of the overall scalp.

An ScPGA response is defined as and ScPGA score clear (0) or almost clear (1) with at least a 2-point reduction from baseline among participants with a baseline ScPGA score ≥ 2.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=199 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=212 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Percentage of Participants With a Scalp Physician Global Assessment (ScPGA) Response at Week 16 Among Participants With Baseline scPGA Score ≥ 2 at Week 16	16.6 Percentage of participants Interval 11.1 to 22.2	44.0 Percentage of participants Interval 37.1 to 51.0	—

SECONDARY outcome

Timeframe: Baseline and Week 16 of the placebo-controlled phase

Population: ITT analysis set (all participants who were randomized) in the placebo-controlled phase with a baseline value and at least one post-baseline value at Week 16

The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if "No," then the subject is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot).

Total scores have a possible range of 0 to 30, with 30 corresponding to the worst health-related quality of life, and 0 corresponding to the best score.

A negative change from baseline indicates an improvement in health-related quality of life scores.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=249 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=261 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16	-2.4 Scores on a scale Standard Error 0.3	-5.2 Scores on a scale Standard Error 0.3	—

SECONDARY outcome

Timeframe: Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up)

Population: Safety analysis set: all randomized participants who received at least 1 dose of treatment. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.

An adverse event (AE) is An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A TEAE is any AE that occurs following administration of study treatment.

Frequency of TEAEs was assessed as well as severity and treatment relatedness.

A TEAE was considered severe based on the Investigator's assessment. A TEAE could be severe if it was serious or non-serious, had symptoms causing discomfort or pain, requiring medical or surgical attention or intervention, interfered with activities of daily life and if drug therapy was required.

Outcome measures

Measure	Placebo-controlled Phase: Placebo n=296 Participants Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=298 Participants Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase n=544 Participants All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any TEAE	139 Participants	195 Participants	351 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Severe TEAE	2 Participants	8 Participants	24 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Treatment-related TEAE	36 Participants	110 Participants	186 Participants

Adverse Events

Placebo-controlled Phase: Placebo

Serious events: 4 serious events

Other events: 51 other events

Deaths: 0 deaths

Placebo-controlled Phase: Apremilast 30 mg

Serious events: 1 serious events

Other events: 118 other events

Deaths: 0 deaths

Apremalist: Placebo-controlled Phase and Extension Phase

Serious events: 12 serious events

Other events: 208 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo-controlled Phase: Placebo n=296 participants at risk Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=298 participants at risk Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase n=544 participants at risk All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32).
Cardiac disorders Angina pectoris	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.34% 1/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Cardiac disorders Cardiac failure	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Cardiac disorders Cardiac failure congestive	0.34% 1/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Cardiac disorders Myocardial infarction	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Cardiac disorders Myocardial ischaemia	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.34% 1/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Gastrointestinal disorders Abdominal pain	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Gastrointestinal disorders Intestinal perforation	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Gastrointestinal disorders Oral disorder	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Infections and infestations Cellulitis	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Infections and infestations Pneumonia	0.34% 1/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.55% 3/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Infections and infestations Pneumonia pneumococcal	0.34% 1/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.18% 1/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Nervous system disorders Migraine without aura	0.34% 1/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.34% 1/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	0.00% 0/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.

Other adverse events

Measure	Placebo-controlled Phase: Placebo n=296 participants at risk Participants received placebo as oral tablets twice daily (BID) for up to 16 weeks (Week 0 to Week 16).	Placebo-controlled Phase: Apremilast 30 mg n=298 participants at risk Participants received apremilast 30 mg as oral tablets BID for up to 16 weeks (Week 0 to Week 16).	Apremalist: Placebo-controlled Phase and Extension Phase n=544 participants at risk All participants who received apremalist 30 mg as oral tablets BID in either the placebo-controlled phase (Week 0 to Week 16), the apremilast extension phase (Week 16 to Week 32), or both phases (Week 0 to Week 32).
Gastrointestinal disorders Diarrhoea	5.1% 15/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	16.4% 49/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	14.3% 78/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Gastrointestinal disorders Nausea	4.4% 13/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	12.8% 38/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	12.7% 69/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Infections and infestations Nasopharyngitis	2.7% 8/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	7.4% 22/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	6.8% 37/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Infections and infestations Upper respiratory tract infection	5.1% 15/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	5.7% 17/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	8.5% 46/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.
Nervous system disorders Headache	5.1% 15/296 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	13.1% 39/298 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.	12.9% 70/544 • Placebo: Day 1 to Week 16; Apremilast Day 1 to a maximum of Week 32 (plus 4 week safety follow-up) The safety analysis set includes all randomized participants who received at least 1 dose of investigational product. One participant randomized to the placebo group received apremilast and was therefore allocated to the apremilast group for the safety analysis.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER