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Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects with Active Psoriatic Arthritis.

Summary
EudraCT number	2010-018385-23
Trial protocol	DE HU AT FR GB ES
Global end of trial date	27 Oct 2016

Results information
Results version number	v1(current)
This version publication date	12 Nov 2017
First version publication date	12 Nov 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-PSA-002

ISRCTN number

US NCT number

NCT01172938

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

Nikolay Delev, Senior Director, Clinical Research and Development, M.D., Celgene Corporation, 01 908-897-5662, ndelev@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

16 Feb 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

To evaluate the clinical efficacy of 2 doses of apremilast (20 mg or 30 mg orally twice per day [BID]), compared with placebo, on the signs and symptoms of psoriatic arthritis (PsA) after 16 weeks’ administration.

Protection of trial subjects

Patient Confidentiality, Personal Data Protection and Biomarker Consent

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Jun 2010

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Ethical reason, Regulatory reason

Long term follow-up duration

5 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 21

Country: Number of subjects enrolled

Austria: 5

Country: Number of subjects enrolled

Canada: 88

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Germany: 10

Country: Number of subjects enrolled

Hungary: 30

Country: Number of subjects enrolled

New Zealand: 20

Country: Number of subjects enrolled

Poland: 45

Country: Number of subjects enrolled

Russian Federation: 44

Country: Number of subjects enrolled

South Africa: 74

Country: Number of subjects enrolled

Spain: 15

Country: Number of subjects enrolled

United Kingdom: 14

Country: Number of subjects enrolled

United States: 135

Worldwide total number of subjects

504

EEA total number of subjects

122

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)

452

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was a multicenter study with 83 study sites from the US, Canada, Europe, Russia, Australia, New Zealand and South Africa.

Screening details

The study population was restricted to male and female subjects ≥ 18 years of age with moderate to severe Psoriatic Arthritis (PsA). Participants must have had a diagnosis of PsA by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, including peripheral joint involvement.

Period 1 title

Placebo-controlled Phase (Week 0-24)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Blinding to treatment assignment was maintained at all sites until after the Week 52 database lock at Year 1, after all Week 52 analyses were completed and the results were released. At that time, active medication was provided. The blind was otherwise not to be broken during the study unless, in the opinion of the doctor, it was necessary to safely treat the subject.

Are arms mutually exclusive

Yes

Placebo

Arm description

Subjects initially randomized to receive placebo tablets twice daily in the 24-week placebo-controlled phase. Subjects who did not have at least 20% improvement in swollen and tender joint counts at Week 16 were re-randomized to either 20 mg or 30 mg apremilast twice daily (early escape).

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

Identically matched placebo tablets BID during the placebo controlled phase.

Apremilast 20 mg

Arm description

Subjects initially randomized to receive 20 mg apremilast tablets twice daily in the placebo-controlled phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets BID during the placebo controlled phase.

Apremilast 30 mg

Arm description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID during the placebo controlled phase.

Number of subjects in period 1	Placebo	Apremilast 20 mg	Apremilast 30 mg
Started	168	168	168
Received Treatment	168	168	168
Completed Week (Wk) 16	158	158	154
Early Escape (EE) at Week 16	107 ^[1]	78 ^[2]	58 ^[3]
Completed	150	146	148
Not completed	18	22	20
Adverse event, serious fatal	-	1	-
Consent withdrawn by subject	2	5	3
Adverse event, non-fatal	11	8	10
Not specified	-	2	1
Non-compliance with study drug	-	1	2
Lack of efficacy	4	5	4
Protocol deviation	1	-	-

Notes
[1] - 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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.
[2] - 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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.
[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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.

Period 2 title

Active Treatment Phase (Weeks 25-52)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

Yes

Apremilast 20 mg

Arm description

Subjects initially randomized to 20 mg apremilast tablets twice daily (BID) in the placebo-controlled phase continued to receive 20 mg apremilast tablets BID in the active treatment.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Apremilast 30 mg

Arm description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 30 mg apremilast tablets BIDin the active treatment phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID

Placebo / Apremilast 20 mg EE

Arm description

Subjects initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 continued to receive 20 mg apremilast during the active-treatment phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets BID

Placebo / Apremilast 20 mg XO

Arm description

Subjects initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) continued to receive 20 mg apremilast tablets BID during the active-treatment phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets BID

Placebo / Apremilast 30 mg EE

Arm description

Subjects initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 continued to receive 30 mg apremilast tablets BID during the active-treatment phase

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID

Placebo / Apremilast 30 mg XO

Arm description

Subjects initially randomized to receive placebo twice daily who were re-randomized at Week 24 continued to receive 30 mg apremilast tablets BID during the active-treatment phase

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets BID

Number of subjects in period 2 ^[4]	Apremilast 20 mg	Apremilast 30 mg	Placebo / Apremilast 20 mg EE	Placebo / Apremilast 20 mg XO	Placebo / Apremilast 30 mg EE	Placebo / Apremilast 30 mg XO
Started	136	145	51	23	49	24
Completed	124	130	44	19	34	22
Not completed	12	15	7	4	15	2
Consent withdrawn by subject	5	1	2	2	9	1
Adverse event, non-fatal	2	5	1	1	2	-
Not specified	-	-	-	-	1	1
Non-compliance with study drug	-	1	-	-	-	-
Lost to follow-up	1	1	1	-	-	-
Lack of efficacy	4	7	3	1	3	-

Notes
[4] - 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 number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.

Period 3 title

Active-Treatment Phase (Weeks 52-104)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Apremilast 20 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Apremilast 30 mg

Arm description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 30 mg apremilast tablets BID in the active treatment / long-term safety phase

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Arm description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast at Week 16 or Week 24 and continued receiving apremilast 20 mg BID in the active treatment / long-term safety phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast at Week 16 or Week 24 and continued receiving apremilast 20 mg BID for up to 4.5 years in the active treatment / long-term safety phase.

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Arm description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast 30 mg tablets BID at Week 16 or Week 24 and continued receiving apremilast 30 mg BID in the active treatment / long-term safety phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Number of subjects in period 3 ^[5]	Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)	Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)
Started	118	121	61	49
Completed	95	100	46	45
Not completed	23	21	15	4
Adverse event, serious fatal	-	1	-	-
Consent withdrawn by subject	10	8	5	2
Adverse event, non-fatal	2	1	3	1
Miscellaneous	2	-	-	1
Non-compliance with study drug	-	2	-	-
Lost to follow-up	1	1	3	-
Missing	1	-	-	-
Lack of efficacy	7	8	4	-

Notes
[5] - 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 number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.

Period 4 title

Active-Treatment Phase Weeks (104-156)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Apremilast 20 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Apremilast 30 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Arm description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast at Week 16 or Week 24 and continued to receive apremilast 20 mg BID in the active treatment / long-term safety phase. After 30 mg apremilast BID was identified as the optimal dose, all subjects originally receiving 20 mg apremilast BID were switched to the 30 mg apremilast BID dose.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Number of subjects in period 4	Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)	Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)
Started	95	100	46	45
Completed	84	93	41	41
Not completed	11	7	5	4
Adverse event, serious fatal	-	-	1	-
Consent withdrawn by subject	6	3	2	1
Adverse event, non-fatal	-	-	-	1
Miscellaneious	-	2	-	-
Lost to follow-up	1	-	-	-
Lack of efficacy	4	2	2	2

Period 5 title

Active-Treatment Phase (Weeks 156-208)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Apremilast 20 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Apremilast 30 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Arm description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast 30 mg tablets BID at Week 16 or Week 24 and continued to receive apremilast 30 mg BID in the active treatment / long-term safety phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Number of subjects in period 5	Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)	Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)
Started	84	93	41	41
Completed	75	88	32	34
Not completed	9	5	9	7
Consent withdrawn by subject	4	2	2	4
Adverse event, non-fatal	4	1	3	-
Miscellaneous	-	-	1	-
Lost to follow-up	-	1	-	1
Lack of efficacy	1	1	3	2

Period 6 title

Active-Treatment Phase (Weeks 208-260)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Apremilast 20 mg

Arm description

Subjects initially randomized to 20 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 20 mg apremilast tablets BID in the active treatment / long-term safety phase. After 30 mg apremilast BID was identified as the optimal dose, all subjects originally receiving 20 mg apremilast BID were switched to the 30 mg apremilast BID dose

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Apremilast 30 mg

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Arm description

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 20 mg tablets PO BID

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Arm description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast 30 mg tablets BID at Week 16 or Week 24 and continued to receive apremilast 30 mg BID in the active treatment / long-term safety phase.

Arm type

Experimental

Investigational medicinal product name

CC-10004

Investigational medicinal product code

Other name

Otezla

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Apremilast 30 mg tablets PO BID

Number of subjects in period 6	Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)	Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)
Started	75	88	32	34
Switched from 20 mg to 30 mg BID	62 ^[6]	0 ^[7]	25 ^[8]	0 ^[9]
Completed	72	80	29	32
Not completed	3	8	3	2
Adverse event, serious fatal	-	1	-	-
Consent withdrawn by subject	2	3	1	-
Adverse event, non-fatal	-	1	1	1
Non-compliance with study drug	1	-	1	-
Lost to follow-up	-	1	-	-
Lack of efficacy	-	2	-	-
Protocol deviation	-	-	-	1

Notes
[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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.
[7] - 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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.
[8] - 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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.
[9] - 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: The number of subjects starting the subsequent period will be less than or equal to the number completing the preceding period, this is because not all subjects who completed the preceding period will enter the subsequent period.

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Apremilast 20 mg

Reporting group description

Subjects initially randomized to receive 20 mg apremilast tablets twice daily in the placebo-controlled phase.

Reporting group title

Apremilast 30 mg

Reporting group description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase.

Reporting group values	Placebo	Apremilast 20 mg	Apremilast 30 mg	Total
Number of subjects	168	168	168	504
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	149	157	146	452
From 65-84 years	19	11	22	52
85 years and over	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.1 ( 12.13 )	48.7 ( 10.99 )	51.4 ( 11.72 )	-
Gender, Male/Female
Units: Subjects
Female	80	83	92	255
Male	88	85	76	249
Study Specific Characteristic \| Duration of psoriatic arthritis
Units: years
arithmetic mean (standard deviation)	7.31 ( 7.118 )	7.18 ( 6.842 )	8.09 ( 8.092 )	-

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

Apremilast 20 mg

Reporting group description

Subjects initially randomized to receive 20 mg apremilast tablets twice daily in the placebo-controlled phase.

Reporting group title

Apremilast 30 mg

Reporting group description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase.

Reporting group title

Apremilast 20 mg

Reporting group description

Subjects initially randomized to 20 mg apremilast tablets twice daily (BID) in the placebo-controlled phase continued to receive 20 mg apremilast tablets BID in the active treatment.

Reporting group title

Apremilast 30 mg

Reporting group description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID) in the placebo-controlled phase and continued to receive 30 mg apremilast tablets BIDin the active treatment phase.

Reporting group title

Placebo / Apremilast 20 mg EE

Reporting group description

Subjects initially randomized to receive placebo twice daily who were re-randomized due to early escape (EE) at Week 16 continued to receive 20 mg apremilast during the active-treatment phase.

Reporting group title

Placebo / Apremilast 20 mg XO

Reporting group description

Subjects initially randomized to receive placebo twice daily who were re-randomized at Week 24 (XO) continued to receive 20 mg apremilast tablets BID during the active-treatment phase.

Reporting group title

Placebo / Apremilast 30 mg EE

Reporting group description

Reporting group title

Placebo / Apremilast 30 mg XO

Reporting group description

Subjects initially randomized to receive placebo twice daily who were re-randomized at Week 24 continued to receive 30 mg apremilast tablets BID during the active-treatment phase

Reporting group title

Apremilast 20 mg

Reporting group description

Reporting group title

Apremilast 30 mg

Reporting group description

Reporting group title

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Apremilast 20 mg

Reporting group description

Reporting group title

Apremilast 30 mg

Reporting group description

Reporting group title

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Apremilast 20 mg

Reporting group description

Reporting group title

Apremilast 30 mg

Reporting group description

Reporting group title

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast 30 mg tablets BID at Week 16 or Week 24 and continued to receive apremilast 30 mg BID in the active treatment / long-term safety phase.

Reporting group title

Apremilast 20 mg

Reporting group description

Reporting group title

Apremilast 30 mg

Reporting group description

Reporting group title

Placebo/Apremilast 20 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Reporting group title

Placebo/Apremilast 30 mg (Active-Treatment/Long-Term Safety)

Reporting group description

Subjects initially randomized to placebo tablets BID during the placebo controlled phase and were re-randomized to apremilast 30 mg tablets BID at Week 16 or Week 24 and continued to receive apremilast 30 mg BID in the active treatment / long-term safety phase.

Subject analysis set title

Placebo / Apremilast 20 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 20 mg apremilast twice daily.

Subject analysis set title

Placebo / Apremilast 30 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects who received placebo twice daily up to Week 16 or Week 24 and were then re-randomized to receive 30 mg apremilast twice daily.

Subject analysis set title

Apremilast 20 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects initially randomized to 20 mg apremilast tablets twice daily (BID).

Subject analysis set title

Apremilast 30 mg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subjects initially randomized to 30 mg apremilast tablets twice daily (BID).

Subject analysis set title

Apremilast 20 mg (Pre-switch)

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects randomized or re-randomized to apremilast 20 mg BID ; only the Only the TEAEs that occurred during apremilast 20 mg BID treatment (before the switch to 30 mg apremilast) were included.

Subject analysis set title

Apremilast 20 mg/30 mg BID (post-switch)

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who switched from apremilast 20 mg BID to apremilast 30 mg BID. Only the TEAEs that occurred during APR 30 mg BID treatment were counted.

Subject analysis set title

Apremilast 30 mg BID

Subject analysis set type

Safety analysis

Subject analysis set description

Participants who were treated with apremilast 30 mg BID throughout the study regardless of when their apremilast-exposure started (at Weeks 0, 16, or 24).

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16

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End point title

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16

End point description

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set (FAS) consisting of all participants randomized as specified in the protocol. Participants who withdrew early or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

End point type

Primary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	19.0	30.4	38.1

Statistical Analysis 1

Statistical analysis description

In order to maintain the Type 1 error at the 0.05 significance level, the Hochberg procedure was to be used. The results of the endpoint were to be considered statistically significant if both the 30 mg apremilast dose versus placebo comparison and the 20 mg versus placebo comparison were statistically significant at the 0.05 significance level, or one of the comparisons was statistically significant at the 0.025 level.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

28.3

Notes
[1] - Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% confidence interval (CI) is based on a normal approximation to the weighted average.
[2] - 2-sided p-value is based on the Cochran-Mantel-Haenszel (CMH) test adjusting for baseline disease modifying antirheumatic drug (DMARD) use.

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.0166 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

11.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

20.4

Notes
[3] - Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the CMH weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
[4] - 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16

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End point title

Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; Last observation carried forward (LOCF) imputation was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	165	163	159
Units: units on a scale
least squares mean (standard error)	-0.086 ( 0.0360 )	-0.198 ( 0.0364 )	-0.244 ( 0.0364 )

Statistical Analysis 1

Statistical analysis description

Pairwise comparisons (30 mg vs placebo and 20 mg vs placebo) were conducted conditional on the primary endpoint results. If the primary endpoint was statistically significant for both apremilast dose groups, pairwise comparisons for the HAQ-DI were to be evaluated at the 0.05 level using the Hochberg procedure. If only one apremilast dose was statistically significant, then only the comparison between that apremilast dose and placebo was conducted for the HAQ-DI score, at the 0.025 level.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017 ^[5]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.159

Confidence interval

level

95%

sides

2-sided

lower limit

-0.258

upper limit

-0.06

Notes
[5] - Based on an ANCOVA model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0252 ^[6]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.113

Confidence interval

level

95%

sides

2-sided

lower limit

-0.211

upper limit

-0.014

Notes
[6] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Secondary: Percentage of Participants With an ACR 20 Response at Week 24

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End point title

Percentage of Participants With an ACR 20 Response at Week 24

End point description

Percentage of participants with an American College of Rheumatology 20% (ACR20) response at Week 24. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	13.1	25.6	35.1

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

< 0.0001 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

22.2

Confidence interval

level

95%

sides

2-sided

lower limit

13.4

upper limit

30.9

Notes
[7] - Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
[8] - The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.

Statistical Analysis 2

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.0038 ^[10]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

12.4

Confidence interval

level

95%

sides

2-sided

lower limit

4.2

upper limit

20.7

Notes
[9] - Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
[10] - The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24

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End point title

Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	165	163	161
Units: units on a scale
least squares mean (standard error)	-0.076 ( 0.0369 )	-0.211 ( 0.0373 )	-0.258 ( 0.0371 )

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005 ^[11]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.182

Confidence interval

level

95%

sides

2-sided

lower limit

-0.283

upper limit

-0.08

Notes
[11] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate

Statistical Analysis 2

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0091 ^[12]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-0.135

Confidence interval

level

95%

sides

2-sided

lower limit

-0.236

upper limit

-0.034

Notes
[12] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Secondary: Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

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End point title

Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

End point description

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	163	163	159
Units: units on a scale
least squares mean (standard error)	1.81 ( 0.621 )	3.50 ( 0.625 )	4.23 ( 0.625 )

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0056 ^[13]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

2.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

4.13

Notes
[13] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0504 ^[14]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

3.4

Notes
[14] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

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End point title

Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

End point description

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase, respectively, from baseline by ≥ 20 mm VAS. Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	29.8	38.7	46.4

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

P-value

= 0.0017 ^[16]

Method

Cochran-Mantel-Haenszel

Parameter type

Adjusted Difference

Point estimate

16.7

Confidence interval

level

95%

sides

2-sided

lower limit

6.6

upper limit

26.8

Notes
[15] - Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.
[16] - The 2-sided p-value is based on the CMH test adjusting for baseline DMARD use.

Statistical Analysis 2

Statistical analysis description

Adjusted difference is the weighted average of the treatment differences across the 2 strata of baseline DMARD use with the Cochran-Mantel-Haenszel (CMH) weights. The 2-sided 95% CI is based on a normal approximation to the weighted average.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

18.9

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 16

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End point title

Change From Baseline in Patient’s Assessment of Pain at Week 16

End point description

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	165	163	159
Units: mm
least squares mean (standard error)	-5.7 ( 1.83 )	-11.5 ( 1.85 )	-13.5 ( 1.85 )

Statistical Analysis 1

Statistical analysis description

Secondary endpoints from the placebo-controlled period (Weeks 16 and 24) were analyzed in a hierarchical fashion to control the Type I error rate as described above.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0023 ^[17]

Method

ANCOVA

Parameter type

LS Mean Difference

Point estimate

-7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-12.9

upper limit

-2.8

Notes
[17] - Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Statistical Analysis 2

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

-0.7

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16

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End point title

Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16

End point description

The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) and at least 1 postbaseline value at or prior to Week 16 are included; LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	95	100	108
Units: units on a scale
least squares mean (standard error)	-0.9 ( 0.30 )	-1.4 ( 0.29 )	-1.3 ( 0.28 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.4

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.3

Secondary: Change From Baseline in Dactylitis Severity Score at Week 16

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End point title

Change From Baseline in Dactylitis Severity Score at Week 16

End point description

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Full analysis set. Participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	63	56	66
Units: units on a scale
least squares mean (standard error)	-1.4 ( 0.28 )	-1.9 ( 0.31 )	-1.7 ( 0.28 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

129

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

0.4

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

0.3

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16

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End point title

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16

End point description

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0 to 76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	158	160	158
Units: units on a scale
least squares mean (standard error)	-3.84 ( 0.929 )	-8.24 ( 0.926 )	-8.72 ( 0.923 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

316

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-4.88

Confidence interval

level

95%

sides

2-sided

lower limit

-7.41

upper limit

-2.34

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

318

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-4.39

Confidence interval

level

95%

sides

2-sided

lower limit

-6.92

upper limit

-1.86

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 16

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End point title

Change From Baseline in the Disease Activity Score (DAS28) at Week 16

End point description

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the distal interphalangeal (DIP) joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	159	161	154
Units: units on a scale
least squares mean (standard error)	-0.26 ( 0.082 )	-0.73 ( 0.082 )	-0.79 ( 0.083 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

313

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.53

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

-0.31

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.47

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.25

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16

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End point title

Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16

End point description

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 16 are included. LOCF was used.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	162	163	159
Units: units on a scale
least squares mean (standard error)	1.55 ( 0.693 )	1.68 ( 0.696 )	3.88 ( 0.695 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

321

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

2.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

4.23

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

-1.77

upper limit

2.03

Secondary: Change from Baseline in SF-36 Physical Function at Week 24

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End point title

Change from Baseline in SF-36 Physical Function at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	163	163	161
Units: units on a scale
least squares mean (standard error)	1.45 ( 0.671 )	3.49 ( 0.675 )	5.01 ( 0.671 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.72

upper limit

5.4

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

3.88

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24

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End point title

Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	18.5	31.0	42.9

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

15.2

upper limit

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

12.4

Confidence interval

level

95%

sides

2-sided

lower limit

3.4

upper limit

21.5

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 24

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End point title

Change From Baseline in Patient’s Assessment of Pain at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	165	163	162
Units: mm
least squares mean (standard error)	-4.2 ( 1.78 )	-11.2 ( 1.79 )	-14.7 ( 1.77 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

327

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

-10.6

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

-5.7

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-12

upper limit

-2.2

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24

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End point title

Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	96	100	110
Units: units on a scale
least squares mean (standard error)	-0.8 ( 0.31 )	-1.6 ( 0.30 )	-1.6 ( 0.29 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

206

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean DIfference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

0.1

Secondary: Change From Baseline in Dactylitis Severity Score at Week 24

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End point title

Change From Baseline in Dactylitis Severity Score at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	56	66
Units: units on a scale
least squares mean (standard error)	-1.3 ( 0.27 )	-2.0 ( 0.30 )	-1.8 ( 0.27 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

130

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.2

upper limit

0.3

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

120

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

0.1

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

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End point title

Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

End point description

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8; Low Disease Activity: > 2.8 and ≤ 10; Moderate Disease Activity: > 10 and ≤ 22; High Disease Activity: > 22. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	158	161	161
Units: units on a scale
least squares mean (standard error)	-3.14 ( 0.965 )	-7.55 ( 0.958 )	-9.52 ( 0.949 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean Difference

Point estimate

-6.38

Confidence interval

level

95%

sides

2-sided

lower limit

-9

upper limit

-3.75

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

319

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean Difference

Point estimate

-4.41

Confidence interval

level

95%

sides

2-sided

lower limit

-7.03

upper limit

-1.79

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 24

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End point title

Change From Baseline in the Disease Activity Score (DAS28) at Week 24

End point description

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. Full analysis set; participants with a baseline value and at least 1 postbaseline value at or prior to Week 24 are included; LOCF imputation was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	161	161	159
Units: units on a scale
least squares mean (standard error)	-0.20 ( 0.087 )	-0.66 ( 0.087 )	-0.90 ( 0.087 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

-0.46

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

322

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean Difference

Point estimate

-0.46

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.22

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24

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End point title

Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24

End point description

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	163	163	161
Units: units on a scale
least squares mean (standard error)	1.12 ( 0.691 )	1.52 ( 0.696 )	3.33 ( 0.690 )

Statistical Analysis 1

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

324

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS mean Difference

Point estimate

2.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

4.1

Statistical Analysis 2

Statistical analysis description

Based on an analysis of covariance (ANCOVA) model with treatment group and baseline DMARD use as factors, and the baseline value as a covariate.

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

326

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

LS Mean DIfference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.29

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 16

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End point title

Percentage of Participants With MASES Improvement ≥ 20% at Week 16

End point description

Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	98	103	114
Units: percentage of participants
number (not applicable)	49.0	56.3	52.6

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

16.7

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

21.1

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16

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End point title

Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Full analysis set; participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	68	59	68
Units: percentage of participants
number (not applicable)	57.4	66.1	60.3

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13.4

upper limit

19.3

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

24.6

Secondary: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16

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End point title

Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16

End point description

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	29.8	46.4	48.8

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

19.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

29.3

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

16.6

Confidence interval

level

95%

sides

2-sided

lower limit

6.4

upper limit

26.8

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 24

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End point title

Percentage of Participants With MASES Improvement ≥ 20% at Week 24

End point description

Percentage of subjects with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. FAS; subjects with a baseline MASES > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for those who escaped early at subjects who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	98	103	114
Units: percentage of participants
number (not applicable)	46.9	58.3	60.5

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

13.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

26.5

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

11.3

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24

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End point title

Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Full analysis set; participants with a baseline dactylitis severity score > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	68	59	68
Units: percentage of participants
number (not applicable)	60.3	69.5	69.1

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

8.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.8

upper limit

24.6

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

24.2

Secondary: Percentage of Participants With Good or Moderate EULAR Response at Week 24

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End point title

Percentage of Participants With Good or Moderate EULAR Response at Week 24

End point description

EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	16.1	30.4	42.3

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

26.3

Confidence interval

level

95%

sides

2-sided

lower limit

17.1

upper limit

35.5

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

14.2

Confidence interval

level

95%

sides

2-sided

lower limit

5.4

upper limit

23.1

Secondary: Percentage of Participants With a ACR 50 Response at Week 16

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End point title

Percentage of Participants With a ACR 50 Response at Week 16

End point description

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	6.0	15.5	16.1

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

10.3

Confidence interval

level

95%

sides

2-sided

lower limit

3.7

upper limit

16.8

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

9.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

Secondary: Percentage of Participants With an ACR 70 Response at Week 16

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End point title

Percentage of Participants With an ACR 70 Response at Week 16

End point description

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set; Participants who discontinued early, or who did not have sufficient data for a definitive determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	1.2	6.0	4.2

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

6.5

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

8.7

Secondary: Percentage of Participants With an ACR 50 Response at Week 24

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End point title

Percentage of Participants With an ACR 50 Response at Week 24

End point description

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	4.2	14.3	19.0

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

14.9

Confidence interval

level

95%

sides

2-sided

lower limit

8.3

upper limit

21.5

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

10.1

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

16.1

Secondary: Percentage of Participants With a ACR 70 Response at Week 24

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End point title

Percentage of Participants With a ACR 70 Response at Week 24

End point description

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Full analysis set; Participants who discontinued early, escaped early at Week 16 or who did not have sufficient data for a definitive determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Baseline and week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: percentage of participants
number (not applicable)	0.6	5.4	10.1

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

9.5

Confidence interval

level

95%

sides

2-sided

lower limit

4.8

upper limit

14.2

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

8.3

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 16

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End point title

Percentage of Participants Achieving a MASES Score of Zero at Week 16

End point description

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 16 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Full analysis set; participants with a baseline MASES > 0 (i.e., pre-existing enthesopathy) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	98	103	114
Units: percentage of participants
number (not applicable)	15.3	27.2	22.8

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

17.9

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

11.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16

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End point title

Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 16 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Full analysis set; participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) are included; LOCF was used. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 16 were counted as non-responders.

End point type

Secondary

End point timeframe

Week 16

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	68	59	68
Units: percentage of participants
number (not applicable)	39.7	42.4	38.2

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

-1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

14.8

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14.8

upper limit

19.6

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 24

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End point title

Percentage of Participants Achieving a MASES Score of Zero at Week 24

End point description

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks of treatment. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. FAS; subjects with a baseline MASES > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for subjects who escaped early at Week 16. Subjects who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	98	103	114
Units: percentage of participants
number (not applicable)	14.3	31.1	31.6

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

212

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

17.4

Confidence interval

level

95%

sides

2-sided

lower limit

6.6

upper limit

28.2

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

16.8

Confidence interval

level

95%

sides

2-sided

lower limit

5.6

upper limit

27.9

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24

Top of page

End point title

Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 24 weeks of treatment. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Full analysis set; participants with a baseline dactylitis severity score > 0 are included; LOCF was used. The Week 16 value was carried over to Week 24 for participants who escaped early at Week 16. Participants who did not have sufficient data (observed or imputed) for a determination of response status at Week 24 were counted as non-responders.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	68	59	68
Units: percentage of participants
number (not applicable)	39.7	49.2	45.6

Statistical Analysis 1

Statistical analysis description

Comparison groups

Placebo v Apremilast 30 mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

22.4

Statistical Analysis 2

Statistical analysis description

Comparison groups

Placebo v Apremilast 20 mg

Number of subjects included in analysis

127

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Difference

Point estimate

8.8

Confidence interval

level

95%

sides

2-sided

lower limit

-8.5

upper limit

26.2

Secondary: Number of Participants with Adverse Events During the Placebo-Controlled Period

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End point title

Number of Participants with Adverse Events During the Placebo-Controlled Period

End point description

A Treatment Emergent Adverse Event (TEAE) is an AE with a start date on or after the date of the first dose of Investigational Product (IP). An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

End point type

Secondary

End point timeframe

Week 0 to Week 16 for placebo participants who entered early escape at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID)

End point values	Placebo	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	168	168	168
Units: participants
Treatment Emergent Adverse Events	81	101	103
Drug-related TEAE	32	54	70
Severe TEAE	6	8	11
Serious TEAE (SAE)	7	8	9
Drug-related Serious AE	2	0	3
TEAE Leading to Drug Interruption	9	10	17
TEAE Leading to Drug Withdrawal	8	10	12
TEAE Leading to Death	0	1	0

No statistical analyses for this end point

Secondary: Number of Participants with Adverse Events During the Apremilast-Exposure Period

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End point title

Number of Participants with Adverse Events During the Apremilast-Exposure Period

End point description

A TEAE is an AE with a start date on or after the date of the first dose of Investigational Product (IP) and no later than 28 days after the last dose of IP. An AE is any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

End point type

Secondary

End point timeframe

Baseline to Week 260; median total exposure to Apremilast was 170 weeks

End point values	Apremilast 20 mg (Pre-switch)	Apremilast 20 mg/30 mg BID (post-switch)	Apremilast 30 mg BID
Number of subjects analysed	245	87	245
Units: participants
Treatment Emergent Adverse Events (TEAEs)	203	39	213
Drug-related TEAE	96	5	131
Severe TEAE	35	1	30
Serious TEAE (SAE)	41	6	49
Drug-related SAE	4	1	9
TEAE leading to drug interruption	47	3	49
TEAE leading to drug withdrawal	27	0	30
TEAE leading to death	1	0	2

No statistical analyses for this end point

Secondary: Percentage of Participants With a ACR 20 Response at Week 52

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End point title

Percentage of Participants With a ACR 20 Response at Week 52

End point description

Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	60	119	130
Units: Participants
number (confidence interval 95%)	53.1 (40.2 to 65.7)	50.0 (36.8 to 63.2)	63.0 (53.7 to 71.7)	54.6 (45.7 to 63.4)

No statistical analyses for this end point

Secondary: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52

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End point title

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52

End point description

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability. The Apremilast Subjects as Randomized/Re-randomized (AAR) Population.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	61	120	132
Units: units on a scale
arithmetic mean (standard deviation)	-0.27 ( 0.562 )	-0.29 ( 0.590 )	-0.37 ( 0.479 )	-0.32 ( 0.547 )

No statistical analyses for this end point

Secondary: Change From Baseline in the SF-36 Physical Functioning Domain at Week 52

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End point title

Change From Baseline in the SF-36 Physical Functioning Domain at Week 52

End point description

The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning. The physical functioning domain assesses limitations in physical activities because of health problems. A positive change from Baseline score indicates an improvement. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	61	120	130
Units: units on a scale
arithmetic mean (standard deviation)	4.46 ( 8.8877 )	4.62 ( 9.979 )	6.98 ( 9.425 )	5.69 ( 8.995 )

No statistical analyses for this end point

Secondary: Percentage of Participants With a Modified PsARC Response at Week 52

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End point title

Percentage of Participants With a Modified PsARC Response at Week 52

End point description

Modified PsARC response is defined as improvement in at least 2 of the 4 measures, at least one of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • 78 tender joint count, • 76 swollen joint count, • Patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • Physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest. Improvement or worsening in joint counts is defined as decrease or increase, respectively, from Baseline by ≥ 30%, and improvement or worsening in global assessments is defined as decrease or increase,from Baseline by ≥ 20 mm VAS. 2-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; includes those who had sufficient data of response status at Week 52

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	61	59	120	129
Units: subjects
number (confidence interval 95%)	73.8 (60.9 to 84.2)	71.2 (57.9 to 82.2)	77.5 (69.0 to 84.6)	73.6 (65.2 to 81.0)

No statistical analyses for this end point

Secondary: Change From Baseline in the Patient Assessment of Pain at Week 52

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End point title

Change From Baseline in the Patient Assessment of Pain at Week 52

End point description

The participant was asked to place a vertical line on a 100-mm visual analog scale on which the left-hand boundary (score = 0 mm) represents "no pain," and the right-hand boundary (score = 100 mm) represents "pain as severe as can be imagined." The distance from the mark to the left-hand boundary was recorded in millimeters. The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	60	120	131
Units: mm
arithmetic mean (standard deviation)	-20.2 ( 26.76 )	-21.0 ( 25.83 )	-17.8 ( 24.50 )	-20.3 ( 23.37 )

No statistical analyses for this end point

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52

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End point title

Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52

End point description

End point type

Secondary

End point timeframe

Baseline and week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	36	36	69	89
Units: units on a scale
arithmetic mean (standard deviation)	-2.2 ( 4.03 )	-1.9 ( 3.89 )	-2.7 ( 2.41 )	-1.9 ( 2.93 )

No statistical analyses for this end point

Secondary: Change From Baseline in the Dactylitis Severity Score at Week 52

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End point title

Change From Baseline in the Dactylitis Severity Score at Week 52

End point description

Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet will be rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a baseline value > 0 (i.e., pre-existing dactylitis) and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	23	26	48	49
Units: units on a scale
arithmetic mean (standard deviation)	-0.8 ( 2.10 )	-2.4 ( 3.58 )	-2.7 ( 3.79 )	-1.8 ( 3.23 )

No statistical analyses for this end point

Secondary: Change From Baseline in the CDAI Score at Week 52

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End point title

Change From Baseline in the CDAI Score at Week 52

End point description

The Clinical Disease Activity Index (CDAI) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: ≤ 2.8 Low Disease Activity: > 2.8 and ≤ 10 Moderate Disease Activity: > 10 and ≤ 22 High Disease Activity: > 22. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	61	59	120	129
Units: units on a scale
arithmetic mean (standard deviation)	-15.00 ( 11.137 )	-14.03 ( 14.900 )	-15.41 ( 13.039 )	-14.54 ( 12.009 )

No statistical analyses for this end point

Secondary: Change From Baseline in the DAS28 at Week 52

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End point title

Change From Baseline in the DAS28 at Week 52

End point description

The DAS28 measures the severity of disease at a specific time and is derived from the following variables: • 28 tender joint count • 28 swollen joint count, which do not include the DIP joints, the hip joint, or the joints below the knee; • C-reactive protein (CRP) • Patient's global assessment of disease activity. DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	60	120	129
Units: units on a scale
arithmetic mean (standard deviation)	-1.47 ( 1.103 )	-1.15 ( 1.272 )	-1.40 ( 1.125 )	-1.31 ( 1.114 )

No statistical analyses for this end point

Secondary: Change From Baseline in the FACIT-Fatigue Scale Score at Week 52

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End point title

Change From Baseline in the FACIT-Fatigue Scale Score at Week 52

End point description

The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from Baseline score indicates an improvement. The Apremilast Subjects as Randomized/Re-randomized (AAR) Population; participants with a Baseline value and a Week 52 value are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	63	61	120	128
Units: units on a scale
arithmetic mean (standard deviation)	4.33 ( 8.183 )	4.15 ( 11.712 )	4.27 ( 8.488 )	3.67 ( 9.078 )

No statistical analyses for this end point

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 52

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End point title

Percentage of Participants With MASES Improvement ≥ 20% at Week 52

End point description

Percentage of participants with pre-existing enthesopathy whose MASES improved by ≥ 20% from Baseline after 52 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	36	36	69	89
Units: percentage of subjects
number (confidence interval 95%)	69.4 (51.9 to 83.7)	55.6 (38.1 to 72.1)	84.1 (73.3 to 91.8)	75.3 (65.0 to 83.8)

No statistical analyses for this end point

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52

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End point title

Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improved by ≥ 1 after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	23	26	48	49
Units: percentage of subjects
number (confidence interval 95%)	65.2 (42.7 to 83.6)	73.1 (52.2 to 88.4)	85.4 (72.2 to 93.9)	77.6 (63.4 to 88.2)

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52

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End point title

Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52

End point description

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS-28 score. A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score less than or equal to 3.2. A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 score of less than or equal to 5.1 or, • an improvement (decrease) in the DAS28 of more than 1.2 and attainment of a DAS28 score of greater than 3.2. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	64	60	120	129
Units: percentage of subjects
number (not applicable)	82.8	70.0	75.0	74.4

No statistical analyses for this end point

Secondary: Percentage of Participants With an ACR 50 Response at Week 52

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End point title

Percentage of Participants With an ACR 50 Response at Week 52

End point description

Percentage of participants with an American College of Rheumatology 50% (ACR50) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in 78 tender joint count; • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	63	61	117	130
Units: percentage of subjects
number (confidence interval 95%)	25.4 (15.3 to 37.9)	27.9 (17.1 to 40.8)	24.8 (17.3 to 33.6)	24.6 (17.5 to 32.9)

No statistical analyses for this end point

Secondary: Percentage of Participants With an ACR 70 Response at Week 52

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End point title

Percentage of Participants With an ACR 70 Response at Week 52

End point description

Percentage of participants with an American College of Rheumatology 70% (ACR70) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in 78 tender joint count; • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein. Two-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Baseline and Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	62	61	117	130
Units: percentage of subjects
number (confidence interval 95%)	4.8 (1.0 to 13.5)	14.8 (7.0 to 26.2)	15.4 (9.4 to 23.2)	13.8 (8.4 to 21.0)

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 52

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End point title

Percentage of Participants Achieving a MASES Score of Zero at Week 52

End point description

Percentage of participants with pre-existing enthesopathy whose MASES improves to 0 after 24 weeks. The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. Two-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; only those participants with a baseline value > 0 (i.e., pre-existing enthesopathy) and who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	36	36	69	89
Units: percentage of subjects
number (confidence interval 95%)	33.3 (18.6 to 51.0)	27.8 (14.2 to 45.2)	50.7 (38.4 to 63.0)	38.2 (28.1 to 49.1)

No statistical analyses for this end point

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52

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End point title

Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52

End point description

Percentage of participants with pre-existing dactylitis whose dactylitis severity score improves to zero after 52 weeks. Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as zero for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present. Two-sided 95% confidence interval is based on the Clopper-Pearson method. Apremilast Subjects as Randomized/Re-randomized (AAR) Population; Participants with a baseline dactylitis severity score > 0 (i.e., pre-existing dactylitis) and who had sufficient data for a definitive determination of response status at Week 52 are included.

End point type

Secondary

End point timeframe

Week 52

End point values	Placebo / Apremilast 20 mg	Placebo / Apremilast 30 mg	Apremilast 20 mg	Apremilast 30 mg
Number of subjects analysed	23	26	48	49
Units: percentage of subjects
number (confidence interval 95%)	52.2 (30.6 to 73.2)	53.8 (33.4 to 73.4)	68.8 (53.7 to 81.3)	68.3 (48.3 to 76.6)

No statistical analyses for this end point

Secondary: Number of Subjects with Adverse Events During the Apremilast-Exposure Period

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End point title

Number of Subjects with Adverse Events During the Apremilast-Exposure Period

End point description

End point type

Secondary

End point timeframe

Baseline to Week 260; median total exposure to Apremilast was 170 weeks

End point values	Apremilast 20 mg (Pre-switch)	Apremilast 20 mg/30 mg BID (post-switch)	Apremilast 30 mg BID
Number of subjects analysed	245	87	245
Units: subjects
Treatment Emergent Adverse Events (TEAEs)	203	39	213
Drug-related TEAE	96	5	131
Severe TEAE	35	1	30
Serious TEAE (SAE)	41	6	49
Drug-related SAE	4	1	9
TEAE Leading to Drug Interruption	47	3	49
TEAE Leading to Drug Withdrawal	27	0	30
TEAE Leading to Death	1	0	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Placebo-controlled Phase: Week 0 to Week 16 for placebo subjects who entered early escape at Week 16 and up to Week 24 for all other subjects. Apremilast-exposure Phase: Baseline to Week 260; median total exposure to Apremilast was 170 weeks

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

V14.0

Reporting group title

Week 0-24: Placebo (Placebo-Controlled Phase)

Reporting group description

Subjects received placebo tablets twice daily during the placebo-controlled phase. Includes data through Week 16 for subjects who escaped early, and through Week 24 for all other subjects.

Reporting group title

Week 0-24: Apremilast 20 mg (Placebo- Controlled Phase)

Reporting group description

Subjects received 20 mg apremilast tablets BID during the 24-week placebo-controlled phase.

Reporting group title

Week 0-24: Apremilast 30 mg (Placebo- Controlled Phase)

Reporting group description

Subjects received 30 mg apremilast tablets BID during the 24-week placebo-controlled phase.

Reporting group title

Apremilast Exposure up to 5 Years: Apremilast 20 mg

Reporting group description

Subjects randomized or re-randomized to apremilast 20 mg BID. Only the TEAEs that occurred during apremilast 20 mg BID treatment (before the switch to 30 mg apremilast) were included

Reporting group title

Apremilast Exposure Up to 5 Years: Apremilast 20/30 mg BID

Reporting group description

Subjects who switched from apremilast 20 mg BID to apremilast 30 mg BID. Only the TEAEs that occurred during APR 30 mg BID treatment were counted.

Reporting group title

Apremilst Exposure up to 5 Years: Apremilast 30 mg BID

Reporting group description

Subjects who were treated with apremilast 30 mg BID throughout the study regardless of when their apremilast-exposure started (at Weeks 0, 16, or 24).

Serious adverse events	Week 0-24: Placebo (Placebo-Controlled Phase)	Week 0-24: Apremilast 20 mg (Placebo- Controlled Phase)	Week 0-24: Apremilast 30 mg (Placebo- Controlled Phase)	Apremilast Exposure up to 5 Years: Apremilast 20 mg	Apremilast Exposure Up to 5 Years: Apremilast 20/30 mg BID	Apremilst Exposure up to 5 Years: Apremilast 30 mg BID
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 168 (4.17%)	8 / 168 (4.76%)	9 / 168 (5.36%)	41 / 245 (16.73%)	6 / 87 (6.90%)	49 / 245 (20.00%)
number of deaths (all causes)	0	1	0	1	0	2
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	2 / 245 (0.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to lymph nodes
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Morton's neuroma
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine tumour
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Shock
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Varicose vein
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Multi-organ failure
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Adnexa uteri cyst
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Benign prostatic hyperplasia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endometriosis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst ruptured
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine haemorrhage
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiectasis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Borderline personality disorder
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	3 / 245 (1.22%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thinking abnormal
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Chest X-ray abnormal
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Chest injury
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Femoral neck fracture
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Joint dislocation
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus lesion
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Traumatic fracture
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 168 (0.60%)	1 / 168 (0.60%)	0 / 168 (0.00%)	2 / 245 (0.82%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	1 / 168 (0.60%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	2 / 245 (0.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Left ventricular dysfunction
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sick sinus syndrome
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Carpal tunnel syndrome
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Convulsion
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Demyelinating polyneuropathy
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sciatica
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Polycythaemia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Conjunctival haemorrhage
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colonic polyp
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	1 / 87 (1.15%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Erythema nodosum
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psoriasis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	5 / 245 (2.04%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 5	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure acute
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Urinary retention
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Goitre
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	2 / 245 (0.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bursitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	1 / 87 (1.15%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	2 / 245 (0.82%)	0 / 87 (0.00%)	3 / 245 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	3 / 245 (1.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vertebral foraminal stenosis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chronic tonsillitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridial infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incision site infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Necrotising fasciitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Osteomyelitis
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 168 (0.60%)	2 / 245 (0.82%)	0 / 87 (0.00%)	2 / 245 (0.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 2	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia legionella
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia streptococcal
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Streptococcal bacteraemia
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	1 / 245 (0.41%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection bacterial
subjects affected / exposed	1 / 168 (0.60%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Yersinia infection
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	1 / 87 (1.15%)	0 / 245 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obesity
subjects affected / exposed	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 168 (0.00%)	0 / 245 (0.00%)	0 / 87 (0.00%)	1 / 245 (0.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Week 0-24: Placebo (Placebo-Controlled Phase)	Week 0-24: Apremilast 20 mg (Placebo- Controlled Phase)	Week 0-24: Apremilast 30 mg (Placebo- Controlled Phase)	Apremilast Exposure up to 5 Years: Apremilast 20 mg	Apremilast Exposure Up to 5 Years: Apremilast 20/30 mg BID	Apremilst Exposure up to 5 Years: Apremilast 30 mg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	43 / 168 (25.60%)	69 / 168 (41.07%)	80 / 168 (47.62%)	150 / 245 (61.22%)	17 / 87 (19.54%)	169 / 245 (68.98%)
Vascular disorders
Hypertension
subjects affected / exposed	2 / 168 (1.19%)	6 / 168 (3.57%)	2 / 168 (1.19%)	20 / 245 (8.16%)	4 / 87 (4.60%)	26 / 245 (10.61%)
occurrences all number	2	6	2	22	4	30
Nervous system disorders
Headache
subjects affected / exposed	8 / 168 (4.76%)	17 / 168 (10.12%)	18 / 168 (10.71%)	31 / 245 (12.65%)	2 / 87 (2.30%)	34 / 245 (13.88%)
occurrences all number	10	25	21	54	2	54
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 168 (2.38%)	1 / 168 (0.60%)	8 / 168 (4.76%)	11 / 245 (4.49%)	1 / 87 (1.15%)	13 / 245 (5.31%)
occurrences all number	5	1	9	12	2	15
Abdominal pain upper
subjects affected / exposed	2 / 168 (1.19%)	3 / 168 (1.79%)	7 / 168 (4.17%)	5 / 245 (2.04%)	0 / 87 (0.00%)	15 / 245 (6.12%)
occurrences all number	2	3	10	5	0	21
Diarrhoea
subjects affected / exposed	4 / 168 (2.38%)	20 / 168 (11.90%)	32 / 168 (19.05%)	33 / 245 (13.47%)	1 / 87 (1.15%)	51 / 245 (20.82%)
occurrences all number	6	20	37	39	1	62
Dyspepsia
subjects affected / exposed	4 / 168 (2.38%)	4 / 168 (2.38%)	6 / 168 (3.57%)	8 / 245 (3.27%)	1 / 87 (1.15%)	14 / 245 (5.71%)
occurrences all number	4	4	6	8	1	15
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 168 (0.60%)	1 / 168 (0.60%)	5 / 168 (2.98%)	10 / 245 (4.08%)	1 / 87 (1.15%)	19 / 245 (7.76%)
occurrences all number	1	1	6	14	1	23
Nausea
subjects affected / exposed	11 / 168 (6.55%)	16 / 168 (9.52%)	32 / 168 (19.05%)	30 / 245 (12.24%)	0 / 87 (0.00%)	41 / 245 (16.73%)
occurrences all number	12	18	41	35	0	56
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 168 (0.60%)	2 / 168 (1.19%)	0 / 168 (0.00%)	7 / 245 (2.86%)	0 / 87 (0.00%)	14 / 245 (5.71%)
occurrences all number	1	2	0	7	0	19
Depression
subjects affected / exposed	1 / 168 (0.60%)	4 / 168 (2.38%)	1 / 168 (0.60%)	17 / 245 (6.94%)	1 / 87 (1.15%)	10 / 245 (4.08%)
occurrences all number	1	4	1	21	1	11
Insomnia
subjects affected / exposed	3 / 168 (1.79%)	2 / 168 (1.19%)	3 / 168 (1.79%)	13 / 245 (5.31%)	0 / 87 (0.00%)	9 / 245 (3.67%)
occurrences all number	3	2	3	13	0	9
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 168 (0.60%)	1 / 168 (0.60%)	1 / 168 (0.60%)	12 / 245 (4.90%)	0 / 87 (0.00%)	15 / 245 (6.12%)
occurrences all number	1	1	1	16	0	17
Back pain
subjects affected / exposed	2 / 168 (1.19%)	2 / 168 (1.19%)	1 / 168 (0.60%)	14 / 245 (5.71%)	0 / 87 (0.00%)	13 / 245 (5.31%)
occurrences all number	2	2	1	15	0	14
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 168 (1.19%)	2 / 168 (1.19%)	0 / 168 (0.00%)	17 / 245 (6.94%)	3 / 87 (3.45%)	19 / 245 (7.76%)
occurrences all number	2	3	0	22	3	22
Gastroenteritis
subjects affected / exposed	0 / 168 (0.00%)	3 / 168 (1.79%)	3 / 168 (1.79%)	16 / 245 (6.53%)	0 / 87 (0.00%)	11 / 245 (4.49%)
occurrences all number	0	3	3	18	0	11
Nasopharyngitis
subjects affected / exposed	5 / 168 (2.98%)	7 / 168 (4.17%)	8 / 168 (4.76%)	30 / 245 (12.24%)	3 / 87 (3.45%)	31 / 245 (12.65%)
occurrences all number	5	8	10	58	3	58
Sinusitis
subjects affected / exposed	4 / 168 (2.38%)	4 / 168 (2.38%)	4 / 168 (2.38%)	21 / 245 (8.57%)	2 / 87 (2.30%)	21 / 245 (8.57%)
occurrences all number	5	4	4	29	2	34
Upper respiratory tract infection
subjects affected / exposed	6 / 168 (3.57%)	10 / 168 (5.95%)	7 / 168 (4.17%)	41 / 245 (16.73%)	3 / 87 (3.45%)	36 / 245 (14.69%)
occurrences all number	8	10	8	73	3	61
Urinary tract infection
subjects affected / exposed	3 / 168 (1.79%)	3 / 168 (1.79%)	2 / 168 (1.19%)	10 / 245 (4.08%)	3 / 87 (3.45%)	16 / 245 (6.53%)
occurrences all number	5	3	2	22	3	26

More information

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Were there any global substantial amendments to the protocol? Yes

13 May 2010

1. Modification of contraception requirements: Use of non-latex condoms (except those made of natural [animal] membrane) permitted to facilitate inclusion of subjects with latex allergies. For clarification, specified that contraceptive sponges must contain spermicide. Use of a cervical cap deleted according to regulatory agency advice. 2. Addition/modification of questionnaires: EQ-5D added to assess subjects’ health state. Licensed versions of the MOS Sleep Scale and the BASDAI replaced the versions found in publications. 3. Addition of Efficacy Results from Study CC-10004-PSA-001: The efficacy results from the Phase 2 study CC-10004-PSA-001 were added to support the rationale for the Phase 3 protocol. 4. Transfer of emergency contact information from the protocol to the Investigator Study Manual. 5. Clarification of handling of subjects who were assigned to PBO or apremilast during the EE at Week 16. 6. Revision of timing of transition of subjects to the final “optimal” dose of study medication from the time of regulatory approval to the time at which unblinded study data support this decision. 7. Addition of ACR 70 to study endpoints. 8. Focus of analysis of questionnaires on health-related quality of life, rather than pharmacoeconomics. 9. Clarification that subjects who participate in the PK/PD assessments must sign a separate informed consent for these assessments. 10. Clarification of handling of concomitant medications for PsA after Week 52 of the study.

02 Aug 2010

1. Updating of safety information from completed studies: Information from recently completed psoriasis and PsA studies, included in the apremilast Investigator Brochure Version 8 (dated 18 May 2010), were incorporated into this amendment. 2. Removal of restrictions on as-needed NSAIDs and narcotic analgesics: Use of these medications was allowed, except within 48 hours of a study visit. 3. Expansion of Table of Events to clarify the assessments to be performed at each visit. 4. Clarification of handling of serum lipid values above the ULN. 5. Allowance of up to 25 mg/week of parenteral MTX. 6. Allowance of up to 325 mg per day of aspirin (acetylsalicylic acid) for cardiovascular prophylaxis. 7. Clarification in Inclusion Criterion 6 that study subjects must be therapeutic DMARD failures.

28 Jan 2011

1. Modification of protocol language for clarification. 2. Amended the protocol to clarify the language around contraception methods to ensure that we precisely describe acceptable methods of contraception given the global nature of our trials. Added a statement into the protocol to ensure that appropriate education regarding contraception methods is provided by the investigator to the subject. 3. Modification to protocol deleting annual CXRs, allowing local treatment guidelines to dictate when CXRs are performed. 4. Alignment of exclusion criteria related to past malignancies across the entire apremilast Phase 3 program, giving investigators responsibility for determining subject eligibility for previously successfully treated local lesions. 5. Modification of Reasons for Discontinuation to align with what is displayed in the InForm database.

10 Jun 2011

1. Provide correction regarding the Celgene Therapeutic Area Head of the study. 2. Addition of weight determination at the Screening Visit. 3. Addition of a serum pregnancy test at baseline for FCBP. 4. A clarification in Section 6.2, Contraception Education, which directs the investigator to Section 7.2 of the protocol where the specific details regarding acceptable contraception for this study may be found. 5. A clarification in Section 6.6.4, Clinical Laboratory Evaluations, to indicate that a microscopic evaluation will be performed on all urine samples. 6. Modification to Inclusion Criterion Number 14 – The Female Birth Control inclusion criterion was updated to clearly define single or multiple forms of contraception that are acceptable for this study. 7. Addition of a footnote to Inclusion Criterion Number 14 – The Female Birth Control inclusion criterion, which clarifies that the female subject’s chosen form of contraception must be fully effective by the time the female subject receives the first dose of study medication at randomization. 8. Modification to Inclusion Criterion Number 13 – Male Birth Control inclusion criterion, which clarifies that male subjects must use a “male” latex or nonlatex condom. 9. Descriptive text on how to record onset and end dates of SAEs on the SAE Report Form was deleted because it is no longer applicable.

20 Apr 2012

1. Updated the contact information for the Medical Monitor of the study. 2. Modification of Section 4.1 Study Design, Section 8.3 Treatment Administration and Schedule, and Section 10.1 Overview regarding site and subject blinding until completion of the 52 Week double-blind phase. 3. Revision of Section 4.1 regarding the replacement of the SRP with an independent external DMC. 4. Modification of Section 4.2 Study Design Rationale, 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 worsening skin psoriasis. 5. Addition of a footnote to the Adverse Events row in Table of Events, Section 5, (Tables 1 and 2) which reminds investigators to perform vasculitis assessments and/or psychiatric evaluations as appropriate, when adverse events are reported. 6. Revision of the Contraception Education in Section 6.2 and movement of footnote from Section 7.2 to Section 6.2. 7. Addition of Section 6.6.3.1 Vasculitis Assessment providing precautionary guidance to investigators. 8. Addition of Section 6.6.3.2 Psychiatric Evaluation to provide guidance to investigators for the management of subjects identified as having thoughts of suicide, attempted suicide or having major psychiatric illness. 9. Addition of Section 6.6.3.3 Risk Benefit for Long-term Active Treatment providing guidance to investigators regarding radiographs of symptomatic joints. 10. Change to the open-label IP packaging is described in Sections 6.10.1 and 8.5. 11. Addition of a note to Section 7.2, Inclusion Criterion 14, to refer investigators to Section 6.2, Contraception Education. 12. The term “CRF” was changed to “eCRF” globally throughout the document to reflect that data is captured in this study in electronic case report form pages (eCRF).

03 Jul 2012

1. The assessment of the primary efficacy endpoint (ACR 20) was made at Week 16 instead of Week 24. 2. Assessments of enthesitis and dactylitis (in subjects who present with these manifestations of PsA at baseline) were elevated to be secondary rather than exploratory outcome measures. 3. The secondary endpoints were assessed at Week 16, in addition to Weeks 24 and 52. 4. The order of secondary endpoints at Weeks 16, 24, and 52 was modified to coincide with the planned sequence of statistical testing. 5. The modified Psoriatic Arthritis Response Criteria (PsARC) and EULAR response were added as secondary efficacy endpoints. 6. The ACR-N was added as an exploratory endpoint. 7. The health-related quality of life endpoints were assessed at Week 16, in addition to Weeks 24 and 52. 8. Modification of Protocol Section 9.1 Permitted Concomitant Medications to allow use of systemic corticosteroids and DMARDs after the Week 52 study visit for worsening arthritic symptoms of PsA. 9. The statistical approaches for analysis of secondary endpoints were updated. 10. The statistical approaches for subgroup analyses were updated. 11. Citations were included to provide references for the modified PsARC and EULAR response that were added as secondary efficacy outcome measures in this amendment.

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, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects with Active Psoriatic Arthritis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16

Primary: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16

Secondary: Percentage of Participants With an ACR 20 Response at Week 24

Secondary: Percentage of Participants With an ACR 20 Response at Week 24

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24

Secondary: Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24

Secondary: Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

Secondary: Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 16

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 16

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16

Secondary: Change From Baseline in Dactylitis Severity Score at Week 16

Secondary: Change From Baseline in Dactylitis Severity Score at Week 16

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 16

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 16

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16

Secondary: Change from Baseline in SF-36 Physical Function at Week 24

Secondary: Change from Baseline in SF-36 Physical Function at Week 24

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24

Secondary: Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 24

Secondary: Change From Baseline in Patient’s Assessment of Pain at Week 24

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24

Secondary: Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24

Secondary: Change From Baseline in Dactylitis Severity Score at Week 24

Secondary: Change From Baseline in Dactylitis Severity Score at Week 24

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

Secondary: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 24

Secondary: Change From Baseline in the Disease Activity Score (DAS28) at Week 24

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24

Secondary: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 16

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 16

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16

Secondary: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16

Secondary: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 24

Secondary: Percentage of Participants With MASES Improvement ≥ 20% at Week 24

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24

Secondary: Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24

Secondary: Percentage of Participants With Good or Moderate EULAR Response at Week 24

Secondary: Percentage of Participants With Good or Moderate EULAR Response at Week 24

Secondary: Percentage of Participants With a ACR 50 Response at Week 16

Secondary: Percentage of Participants With a ACR 50 Response at Week 16

Secondary: Percentage of Participants With an ACR 70 Response at Week 16

Secondary: Percentage of Participants With an ACR 70 Response at Week 16

Secondary: Percentage of Participants With an ACR 50 Response at Week 24

Secondary: Percentage of Participants With an ACR 50 Response at Week 24

Secondary: Percentage of Participants With a ACR 70 Response at Week 24

Secondary: Percentage of Participants With a ACR 70 Response at Week 24

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 16

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 16

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 24

Secondary: Percentage of Participants Achieving a MASES Score of Zero at Week 24

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24

Secondary: Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24

Secondary: Number of Participants with Adverse Events During the Placebo-Controlled Period

Secondary: Number of Participants with Adverse Events During the Placebo-Controlled Period

Clinical Trial Results:
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects with Active Psoriatic Arthritis.