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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects with Moderate to Severe Plaque Psoriasis

Summary
EudraCT number	2010-019992-30
Trial protocol	AT ES DE DK IT
Global end of trial date	30 Nov 2016

Results information
Results version number	v1(current)
This version publication date	17 Dec 2017
First version publication date	17 Dec 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CC-10004-PSOR-009

ISRCTN number

US NCT number

NCT01232283

WHO universal trial number (UTN)

Sponsor organisation name

Celgene Corporation

Sponsor organisation address

86 Morris Avenue, Summit, United States, 07901

Public contact

Clinical Trial Disclosure, Celgene Corporation, 01 888-260-1599, ClinicalTrialDisclosure@Celgene.com

Scientific contact

Weimin Wendy Zhang, Celgene Corporation, 01 908-514-9788, weizhang@celgene.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

03 Jun 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Nov 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the clinical efficacy of apremilast 30 mg BID, compared with placebo, in subjects with moderate to severe plaque psoriasis.

Protection of trial subjects

Patient Confidentiality, Personal Data Protection

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Nov 2010

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 206

Country: Number of subjects enrolled

Canada: 92

Country: Number of subjects enrolled

Austria: 6

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Germany: 52

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

Spain: 17

Country: Number of subjects enrolled

Switzerland: 7

Worldwide total number of subjects

411

EEA total number of subjects

106

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

375

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 46 study centers in 9 countries.

Screening details

Subjects were eligible who had moderate to severe plaque psoriasis.

Period 1 title

Placebo Controlled Phase (Weeks 0-16)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Treatment assignment blinding remained in effect; the blind was broken when all subjects completed their week 52 visit

Are arms mutually exclusive

Yes

Apremilast

Arm description

Participants initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16)

Placebo

Arm description

Participants initially randomized to identically matching placebo tablets (PBO) BID during the Placebo controlled Phase (Weeks 0-16)

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo (identically-matching) tablets BID during the Placebo-controlled Phase (Weeks 0-16).

Number of subjects in period 1	Apremilast	Placebo
Started	274	137
Received apremilast	272	136
Completed	239	112
Not completed	35	25
Consent withdrawn by subject	9	7
Adverse event, non-fatal	12	8
Not specified	2	1
Noncompliance with study drug	1	-
Lost to follow-up	6	6
Lack of efficacy	3	2
Protocol deviation	2	1

Period 2 title

Maintenance Phase (Weeks 16-32)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Treatment assignment blinding remained in effect; the blind was broken when all subjects completed their week 52 visit

Are arms mutually exclusive

Yes

Apremilast-Apremilast

Arm description

Participants who were initially randomized to apremilast 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16) remained on apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32).

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Maintenance Phase (Weeks 16-32)

Placebo-Apremilast

Arm description

Participants who were initially randomized to placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32)

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Maintenance Phase (Weeks 16-32)

Number of subjects in period 2 ^[1]	Apremilast-Apremilast	Placebo-Apremilast
Started	234	108
Completed	194	100
Not completed	40	8
Consent withdrawn by subject	7	1
Adverse event, non-fatal	8	2
Non-compliance with study drug	1	-
Unspecified	2	-
Lost to follow-up	3	2
Lack of efficacy	19	3

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The Study PSOR-009 protocol allowed subjects to withdraw from the clinical trial at any time. Of the 351 subjects who completed the Placebo-controlled Phase, 9 subjects withdrew from the study for diverse reasons including adverse events, protocol violations and withdrawal by subject. Consequently, a total of 342 subjects entered the Maintenance Phase of the trial.

Period 3 title

Randomized Withdrawal Phase(Weeks 32-52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Assessor

Blinding implementation details

Treatment assignment blinding remained in effect; the blind was broken when all subjects completed their 52 week visit

Are arms mutually exclusive

Yes

APR-APR-Re-randomized to PBO

Arm description

Participants who were initially randomized to apremilast 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with apremilast 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered responders (ie, having a ≥PASI-50 response) were re-randomized to placebo during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who lost PASI-50 response achieved at Week 32, were switched back to apremilast 30 mg BID at the time the loss was observed. Those participants who did not lose at least 50% of the PASI response remained on placebo until Week 52. All participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and received apremilast 30 mg BID for the remainder of their participation.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo (identically-matching) tablets BID during the Randomized Withdrawal Phase (Weeks 32-52).

APR-APR Re-randomized to APR

Arm description

Participants who were initially randomized to apremilast 30 mg tablets BID during the 16-week Placebo-controlled Phase continued dosing with apremilast 30 mg BID through the Maintenance Phase (Weeks 16-32). At week 32, those participants who were considered responders (ie, having a ≥PASI-50 response) were re-randomized to apremilast during the Randomized Withdrawal Phase (Weeks 32-52). Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on APR 30 mg BID for the remainder of their participation.

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Randomized Withdrawal Phase (Weeks 32-52)

APR-APR-APR + optional topicals/phototherapy

Arm description

Participants who were initially randomized to apremilast 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with apremilast 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered non-responders (ie, having a response of <PASI-50), remained on apremilast 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these non-responders received additional topicals or phototherapy. Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on apremilast 30 mg BID for the remainder of their participation.

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Randomized Withdrawal Phase (Weeks 32-52)

PBO-APR-APR + optional topicals/phototherapy

Arm description

Participants who were initially randomized to placebo BID during the 16-week Placebo-controlled Phase (Weeks 0-16) were switched after 16 weeks of treatment to apremilast 30 mg BID and continued dosing with apremilast 30 mg BID during the Maintenance Phase (Weeks 16-32). At week 32, all participants were to maintain apremilast 30 mg BID; those who were non-responders (having a response of <PASI-50), remained on apremilast 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these non-responders received additional topical or phototherapy. All participants who completed the Randomized Withdrawal Phase at week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on apremilast 30 mg BID for the remainder of their participation.

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Randomized Withdrawal Phase (Weeks 32-52)

Number of subjects in period 3 ^[2]	APR-APR-Re-randomized to PBO	APR-APR Re-randomized to APR	APR-APR-APR + optional topicals/phototherapy	PBO-APR-APR + optional topicals/phototherapy
Started	62	61	58	96
Treated with APR+ topicals/phototherapy	0 ^[3]	0 ^[4]	28 ^[5]	17 ^[6]
Completed	50	56	41	84
Not completed	12	5	17	12
Adverse event, serious fatal	1	-	-	-
Consent withdrawn by subject	3	3	3	4
Adverse event, non-fatal	2	1	-	1
Unspecified	-	1	-	-
Lost to follow-up	2	-	1	1
Lack of efficacy	4	-	13	5
Protocol deviation	-	-	-	1

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The Study PSOR-009 protocol allowed subjects to withdraw from the clinical trial at any time. Of the 294 subjects who completed the Maintenance Phase, 17 subjects withdrew from the study for diverse reasons including lack of efficacy and withdrawal by subject. Consequently, a total of 277 subjects entered the Randomized Withdrawal Phase of the trial.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Of the 123 subjects who were originally randomized to APR and who achieved a PASI-75 response at Week 32, 62 subjects were re-randomized to placebo and 50 subjects in this group completed the Randomized Withdrawal Phase. Subjects in this treatment group were not permitted to receive topical and/or phototherapy during the Randomization Withdrawal Phase.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Of the 123 subjects who were originally randomized to APR and who achieved a PASI-75 response at Week 32, 61 subjects were re-randomized to APR and 56 subjects in this group completed the Randomized Withdrawal Phase. Subjects in this treatment group were not permitted to receive topical and/or phototherapy during the Randomization Withdrawal Phase.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Of the 194 subjects who were originally randomized to APR and completed the Maintenance Phase, 13 withdrew from the study for diverse reasons including lack of efficacy and withdrawal by subject. Consequently, a total of 181 subjects entered the Randomized Withdrawal Phase. Among them, 123 subjects were re-randomized (62 to PBO, 61 to APR) and 58 subjects entered this arm. Of the 58 subjects, 28 were treated with topicals and/or phototherapy, and 30 did not receive topical and/or phototherapy
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Of the 100 subjects who were originally randomized to PBO, switched to APR and completed the Maintenance Phase with APR, 4 subjects withdrew from the study for diverse reasons including lack of efficacy and withdrawal by subject. Consequently, a total of 96 subjects entered the Randomization Withdrawal Phase of the trial. Of the 96 subjects in the PBO-APR-APR arm, 17 subjects were treated with topical therapy and/or phototherapy, and 79 subjects did not receive topical and/or phototherapy.

Period 4 title

Long-Term Extension Phase (Weeks 52-260)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Apremilast (Long-Term Extension Phase)

Arm description

Participants who were initially randomized to APR 30 mg BID during the 16-week placebo-controlled phase (Weeks 0-16) continued receiving APR 30 mg BID through the Maintenance Phase (weeks 16-32) and apremilast 30 mg tablets or placebo during the Randomized Withdrawal Phase were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and remained on APR 30 mg BID for the remainder of their participation.

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Long-Term Extension Phase (Weeks 52-260)

Placebo-Apremilast (Long-term extension)

Arm description

Participants who were initially randomized to identically matching placebo BID during the Placebo-controlled Phase (Weeks 0-16) were switched at Week 16 to apremilast 30 mg BID during the Maintenance Phase, received apremilast 30 mg PO BID during the Randomized Withdrawal Phase and then continued to receive apremilast 30 mg tablets BID in the long-term extension phase from weeks 52-260.

Arm type

Experimental

Investigational medicinal product name

Apremilast

Investigational medicinal product code

CC-10004

Other name

Otzela

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the Long-term Extension Phase (Weeks 50-260)

Number of subjects in period 4 ^[7]	Apremilast (Long-Term Extension Phase)	Placebo-Apremilast (Long-term extension)
Started	137	80
Completed	29	19
Not completed	108	61
Adverse event, serious fatal	1	-
Consent withdrawn by subject	30	14
Adverse event, non-fatal	11	6
Miscellaneous	7	3
Non-compliance	3	2
Lost to follow-up	9	6
Lack of efficacy	46	30
Protocol deviation	1	-

Notes
[7] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The Study PSOR-009 protocol allowed subjects to withdraw from the clinical trial at any time. Of the 231 subjects who completed the Randomized Withdrawal Phase, 14 subjects withdrew from the study for diverse reasons including adverse events, lack of efficacy, non-compliance and withdrawal by subject. Consequently, a total of 217 subjects entered the Long-Term Extension of the trial.

Baseline characteristics

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Reporting group title

Apremilast

Reporting group description

Participants initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)

Reporting group title

Placebo

Reporting group description

Participants initially randomized to identically matching placebo tablets (PBO) BID during the Placebo controlled Phase (Weeks 0-16)

Reporting group values	Apremilast	Placebo	Total
Number of subjects	274	137	411
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	252	123	375
From 65-84 years	22	14	36
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	45.3 ± 13.05	45.7 ± 13.38	-
Gender, Male/Female
Units: Subjects
Female	98	37	135
Male	176	100	276
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	1	1	2
Asian	8	6	14
Black or African American	13	2	15
Native Hawaiian or Other Pacific Islander	1	0	1
White	250	128	378
Other-not specified	1	0	1
Study Specific Characteristic \| Duration of Plaque Psoriasis
All participants enrolled were required to have a diagnosis of plaque psoriasis at least 12 months prior to screening, but the duration was not required for enrollment. Overall baseline population for duration of plaque psoriasis in the apremilast arm were 271 participants and 135 for those in the placebo arm.
Units: years
arithmetic mean (standard deviation)	17.94 ± 11.367	18.68 ± 12.088	-

Subject analysis set title

APR: Subjects with TEAEs during the APR-Exposure Phase

Subject analysis set type

Safety analysis

Subject analysis set description

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

Subject analysis set title

APR: Subjects with Psoriasis Flare in the APR-Exposure Phase

Subject analysis set type

Safety analysis

Subject analysis set description

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

Subject analysis sets values	APR: Subjects with TEAEs during the APR-Exposure Phase	APR: Subjects with Psoriasis Flare in the APR-Exposure Phase
Number of subjects	380	380
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age Continuous
Units: years
arithmetic mean (standard deviation)	45.3 ± 13.05	45.7 ± 13.38
Gender, Male/Female
Units: Subjects
Female
Male
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native
Asian
Black or African American
Native Hawaiian or Other Pacific Islander
White
Other-not specified
Study Specific Characteristic \| Duration of Plaque Psoriasis
All participants enrolled were required to have a diagnosis of plaque psoriasis at least 12 months prior to screening, but the duration was not required for enrollment. Overall baseline population for duration of plaque psoriasis in the apremilast arm were 271 participants and 135 for those in the placebo arm.
Units: years
arithmetic mean (standard deviation)	17.94 ± 11.37	18.68 ± 12.088

End points

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Reporting group title

Apremilast

Reporting group description

Participants initially randomized to apremilast (APR) 30 mg tablets twice daily (BID) during the Placebo-controlled Phase (Weeks 0-16)

Reporting group title

Placebo

Reporting group description

Participants initially randomized to identically matching placebo tablets (PBO) BID during the Placebo controlled Phase (Weeks 0-16)

Reporting group title

Apremilast-Apremilast

Reporting group description

Reporting group title

Placebo-Apremilast

Reporting group description

Reporting group title

APR-APR-Re-randomized to PBO

Reporting group description

Reporting group title

APR-APR Re-randomized to APR

Reporting group description

Reporting group title

APR-APR-APR + optional topicals/phototherapy

Reporting group description

Participants who were initially randomized to apremilast 30 mg BID during the 16-week Placebo-controlled Phase continued dosing with apremilast 30 mg BID through the Maintenance Phase (Weeks 16-32). At Week 32, those participants who were considered non-responders (ie, having a response of <PASI-50), remained on apremilast 30 mg BID and were given the option of adding topical therapies and/or phototherapy to their regimen. A subset of these non-responders received additional topicals or phototherapy. Those participants who completed the Randomized Withdrawal Phase at Week 52 were eligible to participate in the Long-term Extension Phase from Weeks 52-260 and continued on apremilast 30 mg BID for the remainder of their participation.

Reporting group title

PBO-APR-APR + optional topicals/phototherapy

Reporting group description

Reporting group title

Apremilast (Long-Term Extension Phase)

Reporting group description

Reporting group title

Placebo-Apremilast (Long-term extension)

Reporting group description

Subject analysis set title

APR: Subjects with TEAEs during the APR-Exposure Phase

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

APR: Subjects with Psoriasis Flare in the APR-Exposure Phase

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Percentage of participants Who Achieved at least a 75% improvement (response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 from Baseline

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End point title

Percentage of participants Who Achieved at least a 75% improvement (response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 from Baseline

End point description

PASI-75 response is the percentage of subjects who achieved at least a 75% reduction (improvement) from baseline in PASI score 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). Full Analysis Set (FAS) consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group in which they were randomized. Last observation carried forward.

End point type

Primary

End point timeframe

Baseline to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	274	137
Units: percentage of participants
number (not applicable)	28.8	5.8

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

16.3

upper limit

29.6

Secondary: Percentage of Participants who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) with at Least 2 Points Reduction from Baseline

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End point title

Percentage of Participants who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) with at Least 2 Points Reduction from Baseline

End point description

The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator must have factored in areas that have already been cleared (ie, have scores of 0) and not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score. The FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	274	137
Units: percentage of participants
number (not applicable)	20.4	4.4

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

16.1

Confidence interval

level

95%

sides

2-sided

lower limit

10.2

upper limit

21.9

Secondary: Percent Change from Baseline in the Affected Body Surface Area (BSA) at Week 16

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End point title

Percent Change from Baseline in the Affected Body Surface Area (BSA) at Week 16

End point description

BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant’s hand (entire palmar surface or “handprint” including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA – baseline BSA) / baseline BSA (%). The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Subjects were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. Subjects with a baseline value and at least 1 post-baseline value were included. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	269	136
Units: percent change
least squares mean (standard error)	-48.40 ± 2.636	-6.25 ± 3.710

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.0001

Method

ANCOVA

Parameter type

Difference in LS Mean

Point estimate

-42.15

Confidence interval

level

95%

sides

2-sided

lower limit

-51.11

upper limit

-33.2

Notes
[1] - The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.

Secondary: Percent Change from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 16

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End point title

Percent Change from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 16

End point description

PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. LOCF imputation was used. Subjects with a baseline value and at least 1 post-baseline value are included.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	269	136
Units: percent change
least squares mean (standard error)	-50.8 ± 2.23	-16.0 ± 3.15

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-34.8

Confidence interval

level

95%

sides

2-sided

lower limit

-42.4

upper limit

-27.2

Notes
[2] - The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.

Secondary: Percentage of Participants Who Achieved a 50% Improvement (response) in the PASI Score (PASI-50) at Week 16 from Baseline

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End point title

Percentage of Participants Who Achieved a 50% Improvement (response) in the PASI Score (PASI-50) at Week 16 from Baseline

End point description

PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The 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. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	274	137
Units: Percentage of Participants
number (not applicable)	55.5	19.7

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

35.8

Confidence interval

level

95%

sides

2-sided

lower limit

26.9

upper limit

44.7

Secondary: Change from Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16

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End point title

Change from Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16

End point description

The Pruritus Visual Analog Scores (VAS) were used to measure the amount of itching and discomfort a participant experiences. Subject's assessment of Pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? All VAS values range from 0 to 100. Higher scores correspond to more severe symptom or disease. Change from baseline was calculated for the VAS scale, where change = visit value − baseline value. The FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. LOCF imputation was used. Subjects with a baseline value and at least 1 post-baseline value are included.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	268	133
Units: units on a scale
least squares mean (standard error)	-33.5 ± 2.08	-12.2 ± 2.95

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

401

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-21.3

Confidence interval

level

95%

sides

2-sided

lower limit

-28.4

upper limit

-14.2

Notes
[3] - The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) total score at Week 16

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End point title

Change from Baseline in Dermatology Life Quality Index (DLQI) total score at Week 16

End point description

DLQI is a practical questionnaire to assess limitations related to the impact of skin disease. DLQI contains 10 items dealing with the subject’s skin. With the exception of Item Number 7, the subject responds on a 4-point scale, ranging from “Very Much” (score 3) to “Not at All” or “Not relevant” (score 0). Item Number 7 is a multi-part item, the first part of which ascertains whether the subjects skin prevented them from working or studying, 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 responses being “A lot,” “A little,” or “Not at all” (scores 2, 1, or 0 respectively). The DLQI total score was derived by summing all item scores, having a range of 0 to 30, with 30 corresponding to the worst quality of life, and 0 to the best. The FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized for the FAS. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	267	131
Units: units on a scale
least squares mean (standard error)	-6.7 ± 0.37	-2.7 ± 0.53

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.0001

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

-2.8

Notes
[4] - The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate.

Secondary: Change from Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16

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End point title

Change from Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16

End point description

The SF-36 was a health instrument consisting of 8 scales: physical function, role limitations–physical, vitality, general health perceptions, bodily pain, social function, role limitations–emotional and mental health. Scale scores range from 0 to 100, with higher scores indicating better health. 2 overall summary scores were obtained − a Physical Component Summary score (PCS) and a Mental Component Summary (MCS) score. Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value − baseline value. The FAS consisted of all subjects who were randomized per protocol. Subjects were included in the treatment group to which they were randomized. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	267	131
Units: units on a scale
least squares mean (standard error)	2.60 ± 0.563	-0.03 ± 0.804

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.0078

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

4.56

Notes
[5] - The model included treatment group as a factor and the baseline value as a covariate. The estimation and p-value were adjusted by the covariate

Secondary: Percentage of Participants Who Achieved Both a 75% Improvement (response) in the PASI and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction at Week 16 from Baseline

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End point title

Percentage of Participants Who Achieved Both a 75% Improvement (response) in the PASI and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction at Week 16 from Baseline

End point description

PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. See Outcome measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See Outcome Measure #2 for further description. The Full Analysis Set (FAS) consisted of all participants who were randomized per protocol. Participants were included in the treatment group to which they were randomized APR 30 BID or placebo for the FAS. LOCF imputation was used.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	274	137
Units: percentage of participants
number (not applicable)	18.6	4.4

Statistical Analysis 1

Comparison groups

Apremilast v Placebo

Number of subjects included in analysis

411

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Chi-squared

Parameter type

Risk difference (RD)

Point estimate

14.2

Confidence interval

level

95%

sides

2-sided

lower limit

8.5

upper limit

Secondary: Time to Loss of Effect (loss of 50% improvement in PASI score obtained at Week 32 compared to baseline) during the Randomized Treatment Withdrawal Phase

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End point title

Time to Loss of Effect (loss of 50% improvement in PASI score obtained at Week 32 compared to baseline) during the Randomized Treatment Withdrawal Phase

End point description

Time to loss was the time between the re-randomization date and the date of the first assessment with loss of 50% PASI improvement (event), or the time between the re-randomization date and the date of the last PASI assessment in the randomized withdrawal phase prior to addition of topical/phototherapy or other effective psoriasis therapies, or resumption of apremilast 30 mg BID, or discontinuation, or Week 52 if no loss (censored), whichever was earlier. Analysis population consisted of participants who were re-randomized to placebo or Apremilast 30mg BID at Week 32.

End point type

Secondary

End point timeframe

Weeks 32 to Week 52

End point values	APR-APR-Re-randomized to PBO	APR-APR Re-randomized to APR
Number of subjects analysed	62	61
Units: Weeks
median (confidence interval 95%)	12.4 (8.3 to 20.1)	21.9 (-99999 to 99999)

Statistical Analysis 1

Comparison groups

APR-APR-Re-randomized to PBO v APR-APR Re-randomized to APR

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

3.408

upper limit

17.399

Secondary: Number of Participants with Adverse Events (AE) in the Placebo Controlled Phase

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End point title

Number of Participants with Adverse Events (AE) in the Placebo Controlled Phase

End point description

An AE was any noxious, unintended, or untoward medical occurrence, that may worsen in a subject during the study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values regardless of cause. Any worsening (ie.,clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE is any untoward AE that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or require intervention to prevent one of the outcomes above. An AE is a treatment emergent if the AE start date is on or after the date of the lst dose of IP and no later than 28 days after the last dose. Safety population = subjects randomized and received at least 1 dose of IP.

End point type

Secondary

End point timeframe

Baseline to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	272	136
Units: participants
Any TEAE	185	82
Any drug related TEAE	106	29
Any Severe TEAE	12	6
Any Serious TEAE	5	3
Any TEAE leading to drug interruption	16	4
Any TEAE leading to drug withdrawal	15	7

No statistical analyses for this end point

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Placebo Controlled Phase

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End point title

Number of Participants with Psoriasis Flare or Rebound in the Placebo Controlled Phase

End point description

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

End point type

Secondary

End point timeframe

Week 0 to Week 16

End point values	Apremilast	Placebo
Number of subjects analysed	272	136
Units: participants
Participants with any psoriasis flare [1]	3	7
Participants with any psoriasis rebound [2]	1	0
PASI ≥ 125% of Baseline score after last dose [3]	1	2

No statistical analyses for this end point

Secondary: Number of Participants with TEAEs During the Apremilast-Exposure Period Through Week 260

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End point title

Number of Participants with TEAEs During the Apremilast-Exposure Period Through Week 260

End point description

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

End point type

Secondary

End point timeframe

Week 0 to Week 260; The mean duration of exposure was 100.66 weeks.

End point values	APR: Subjects with TEAEs during the APR-Exposure Phase
Number of subjects analysed	380
Units: participants
Any TEAE	316
Any Drug-Related TEAE	165
Any Severe TEAE	58
Any Serious TEAE	44
Any Serious Drug-Related TEAE	8
Any TEAE Leading to Drug Interruption	56
Any TEAE Leading to Drug Withdrawal	45
Any TEAE Leading to Death	1

No statistical analyses for this end point

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Apremilast-Exposure Period

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End point title

Number of Participants with Psoriasis Flare or Rebound in the Apremilast-Exposure Period

End point description

End point type

Secondary

End point timeframe

Week 0 to Week 260

End point values	APR: Subjects with Psoriasis Flare in the APR-Exposure Phase
Number of subjects analysed	380
Units: participants
Participants with any psoriasis flare [1]	25
Participants with any psoriasis rebound [2]	11
PASI ≥ 125% of Baseline score after last dose [3]	12

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs are reported at: 1. Weeks 0-16: PBO-controlled phase 2. Weeks 32-52 Randomized Withdrawal participants re-randomized to PBO at Week 32 3. Weeks 0-260 APR-exposure period for participants randomized or switched to APR at any time during the study

Adverse event reporting additional description

During the PBO-controlled Phase (Weeks 0-16), the mean duration of treatment for those randomized to APR 30 BID or PBO at Week 0, was 14.0 and 14.6, respectively; for those re-randomized to PBO at Week 32, the mean duration of PBO was 11.6 weeks; during the APR-Exposure Period (Weeks 0-260), the mean duration of exposure to APR was 100.66 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.0

Reporting group title

Placebo: Weeks 0-16 (PBO-Controlled Phase)

Reporting group description

Participants randomized to identically matching placebo tablets BID during the Placebo-controlled Phase (Weeks 0-16)

Reporting group title

APR-APR-PBO: Weeks 32-52 (Randomized Withdrawal Phase)

Reporting group description

Participants re-randomized to placebo tablets BID at Week 32. Includes data from Week 32 up to Week 52 when participants received placebo treatment.

Reporting group title

Apremilast: Weeks 0-260 (APR-Exposure Period)

Reporting group description

Participants who received apremilast 30 mg tablets BID, regardless of when the apremilast exposure started (at Week 0 or at Week 16), up until Week 260. Adverse events associated with apremilast 30 mg treatment up to Week 260 were included. AEs that started more than 28 days after Placebo treatment and prior to resuming apremilast were excluded for participants who were re-randomized to Placebo at Week 32

Reporting group title

Apremilast: Weeks 0-16 (PBO-Controlled Phase)

Reporting group description

Participants randomized to apremilast 30 mg tablets BID during the Placebo-controlled Phase (Weeks 0-16)

Serious adverse events	Placebo: Weeks 0-16 (PBO-Controlled Phase)	APR-APR-PBO: Weeks 32-52 (Randomized Withdrawal Phase)	Apremilast: Weeks 0-260 (APR-Exposure Period)	Apremilast: Weeks 0-16 (PBO-Controlled Phase)
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 136 (2.21%)	2 / 62 (3.23%)	44 / 380 (11.58%)	5 / 272 (1.84%)
number of deaths (all causes)	0	1	1	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diffuse large B-cell lymphoma
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endometrial cancer
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lip and/or oral cavity cancer
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine cancer
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	1 / 136 (0.74%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Alcoholism
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Personality disorder
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Schizophrenia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Helicobacter test positive
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Laceration
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	1 / 136 (0.74%)	0 / 62 (0.00%)	0 / 380 (0.00%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachyarrhythmia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia paroxysmal
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Haemorrhage intracranial
subjects affected / exposed	0 / 136 (0.00%)	1 / 62 (1.61%)	0 / 380 (0.00%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Parkinson's disease
subjects affected / exposed	0 / 136 (0.00%)	1 / 62 (1.61%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 136 (0.74%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Angle closure glaucoma
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Maculopathy
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	2 / 380 (0.53%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pustular psoriasis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthropathy
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gouty arthritis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc degeneration
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	2 / 380 (0.53%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	2 / 380 (0.53%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung abscess
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	0 / 272 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	0 / 136 (0.00%)	0 / 62 (0.00%)	1 / 380 (0.26%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo: Weeks 0-16 (PBO-Controlled Phase)	APR-APR-PBO: Weeks 32-52 (Randomized Withdrawal Phase)	Apremilast: Weeks 0-260 (APR-Exposure Period)	Apremilast: Weeks 0-16 (PBO-Controlled Phase)
Total subjects affected by non serious adverse events
subjects affected / exposed	38 / 136 (27.94%)	17 / 62 (27.42%)	234 / 380 (61.58%)	128 / 272 (47.06%)
Nervous system disorders
Headache
subjects affected / exposed	1 / 136 (0.74%)	0 / 62 (0.00%)	28 / 380 (7.37%)	17 / 272 (6.25%)
occurrences all number	1	0	52	35
Tension headache
subjects affected / exposed	2 / 136 (1.47%)	0 / 62 (0.00%)	31 / 380 (8.16%)	20 / 272 (7.35%)
occurrences all number	2	0	52	25
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	8 / 136 (5.88%)	1 / 62 (1.61%)	62 / 380 (16.32%)	43 / 272 (15.81%)
occurrences all number	9	1	96	54
Nausea
subjects affected / exposed	9 / 136 (6.62%)	2 / 62 (3.23%)	68 / 380 (17.89%)	50 / 272 (18.38%)
occurrences all number	10	2	91	61
Vomiting
subjects affected / exposed	5 / 136 (3.68%)	0 / 62 (0.00%)	27 / 380 (7.11%)	14 / 272 (5.15%)
occurrences all number	7	0	30	15
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	7 / 136 (5.15%)	1 / 62 (1.61%)	24 / 380 (6.32%)	3 / 272 (1.10%)
occurrences all number	7	1	37	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 136 (1.47%)	2 / 62 (3.23%)	26 / 380 (6.84%)	5 / 272 (1.84%)
occurrences all number	2	3	30	5
Back pain
subjects affected / exposed	2 / 136 (1.47%)	2 / 62 (3.23%)	31 / 380 (8.16%)	6 / 272 (2.21%)
occurrences all number	2	2	42	11
Pain in extremity
subjects affected / exposed	2 / 136 (1.47%)	1 / 62 (1.61%)	19 / 380 (5.00%)	6 / 272 (2.21%)
occurrences all number	3	1	19	6
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 136 (0.00%)	1 / 62 (1.61%)	29 / 380 (7.63%)	4 / 272 (1.47%)
occurrences all number	0	1	39	4
Nasopharyngitis
subjects affected / exposed	6 / 136 (4.41%)	5 / 62 (8.06%)	69 / 380 (18.16%)	20 / 272 (7.35%)
occurrences all number	7	6	118	28
Upper respiratory tract infection
subjects affected / exposed	6 / 136 (4.41%)	1 / 62 (1.61%)	53 / 380 (13.95%)	13 / 272 (4.78%)
occurrences all number	6	1	76	13
Urinary tract infection
subjects affected / exposed	0 / 136 (0.00%)	1 / 62 (1.61%)	22 / 380 (5.79%)	5 / 272 (1.84%)
occurrences all number	0	1	26	6

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Were there any global substantial amendments to the protocol? Yes

05 Jan 2011

1. Clarified procedures for subjects who entered the Randomized Treatment Withdrawal Phase at Week 32 2. Clarified that Arthritis VAS only pertained to subjects with psoriatic arthritis 3. Clarified the language regarding contraception methods to ensure that acceptable methods of contraception by subjects were used and added a statement to ensure that appropriate education regarding contraception methods was provided by the investigator to the subjects 4. Limited sites to North America and Europe 5. Corrected the order of health-related quality of life (HRQoL) and VAS assessments to align with what is actually being done on the SitePad instrument 6. Aligned exclusion criteria related to past malignancies across the entire apremilast Phase 3 program in order to give investigators responsibility for determining subject eligibility for previously successfully treated local lesions 7. Clarified Statistical Efficacy Analysis deleting the “Per-protocol” analysis 8. Modified the Reasons for Discontinuation to align with what is displayed in the InForm database

10 Jun 2011

1. Provided updates to the contact information for the medical monitor of the study 2. Provide correction regarding the Celgene Therapeutic Area Head of the study 3. Clarified the Contraception Education that required the investigator to educate the subject on acceptable birth control any time when a subject’s contraceptive measures or ability to become pregnant changed; modified to direct the investigator to Section 7.2 of the protocol where details regarding the acceptable contraception for this study may be found 4. Modified Inclusion Criterion Number 9 (female birth control) to clearly define single or multiple forms of contraception that were acceptable for this study 5. Added a footnote to Inclusion Criterion Number 9 (female birth control) to clarify that the female subject’s chosen form of contraception must be fully effective by the time the female subject is randomized into the study 6. Modified Inclusion Criterion Number 10 (male birth control) to clarify that male subjects must use a “male” latex or non-latex condom 7. Deleted descriptive text on how to record onset and end dates of SAEs on the SAE Report Form because it is no longer applicable

19 Apr 2012

1. Provided updates to the contact information for the medical monitor of the study 2. Clarified Section 3.2.2, Efficacy, and in Section 3.3, Exploratory Endpoint(s), that the VAS scale endpoints were to be change from baseline rather than percent change 3. Modified Section 4.1, Study Design, to allow the use of topical corticosteroids, retinoids or vitamin D analog preparations and/or phototherapy after the Week 52 study visit for non-responders 4. Modified Section 4.1, Study Design, regarding the replacement of the Safety Review Panel with an independent external DMC 5. Added footnotes to the Tables of Events clarifying that vasculitis assessments and/or psychiatric evaluations were to be performed as appropriate when adverse events were reported 6. Revised the Contraception Education language in Section 6.2 and moved footnote from Section 7.2 to Section 6.2 7. Added Section 6.6.4.1, Vasculitis Assessment, providing guidance to investigators 8. Added Section 6.6.4.2, Psychiatric Evaluation, to provide precautionary guidance to investigators for the management of subjects identified as having thoughts of suicide, attempted suicide or having major psychiatric illness 9. Added open-label IP package description in Section 6.10.1, Investigational Product Dispensing and Counting for Compliance, and Section 8.4, Packaging and Labeling 10. Modified Section 9.1, Permitted Concomitant Medications, and Section 9.2, Prohibited Concomitant Medications, to allow the use of topical corticosteroids, retinoids, or vitamin D analog preparations and/or phototherapy after the Week 52 study visit for non-responders 11. Clarified that AE tables were to summarize treatment-emergent AE only 12. Changed “CRF” to “eCRF” globally throughout the document, to reflect that data captured in this study in electronic case report form pages (eCRF)

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects with Moderate to Severe Plaque Psoriasis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants Who Achieved at least a 75% improvement (response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 from Baseline

Primary: Percentage of participants Who Achieved at least a 75% improvement (response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 from Baseline

Secondary: Percentage of Participants who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) with at Least 2 Points Reduction from Baseline

Secondary: Percentage of Participants who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) with at Least 2 Points Reduction from Baseline

Secondary: Percent Change from Baseline in the Affected Body Surface Area (BSA) at Week 16

Secondary: Percent Change from Baseline in the Affected Body Surface Area (BSA) at Week 16

Secondary: Percent Change from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 16

Secondary: Percent Change from Baseline in the Psoriasis Area Severity Index (PASI) score at Week 16

Secondary: Percentage of Participants Who Achieved a 50% Improvement (response) in the PASI Score (PASI-50) at Week 16 from Baseline

Secondary: Percentage of Participants Who Achieved a 50% Improvement (response) in the PASI Score (PASI-50) at Week 16 from Baseline

Secondary: Change from Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16

Secondary: Change from Baseline in Pruritus Visual Analog Scale (VAS) Score at Week 16

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) total score at Week 16

Secondary: Change from Baseline in Dermatology Life Quality Index (DLQI) total score at Week 16

Secondary: Change from Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16

Secondary: Change from Baseline in the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16

Secondary: Percentage of Participants Who Achieved Both a 75% Improvement (response) in the PASI and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction at Week 16 from Baseline

Secondary: Percentage of Participants Who Achieved Both a 75% Improvement (response) in the PASI and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction at Week 16 from Baseline

Secondary: Time to Loss of Effect (loss of 50% improvement in PASI score obtained at Week 32 compared to baseline) during the Randomized Treatment Withdrawal Phase

Secondary: Time to Loss of Effect (loss of 50% improvement in PASI score obtained at Week 32 compared to baseline) during the Randomized Treatment Withdrawal Phase

Secondary: Number of Participants with Adverse Events (AE) in the Placebo Controlled Phase

Secondary: Number of Participants with Adverse Events (AE) in the Placebo Controlled Phase

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Placebo Controlled Phase

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Placebo Controlled Phase

Secondary: Number of Participants with TEAEs During the Apremilast-Exposure Period Through Week 260

Secondary: Number of Participants with TEAEs During the Apremilast-Exposure Period Through Week 260

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Apremilast-Exposure Period

Secondary: Number of Participants with Psoriasis Flare or Rebound in the Apremilast-Exposure Period

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Apremilast (CC-10004) in Subjects with Moderate to Severe Plaque Psoriasis