Study of Apremilast to Treat Subjects With Active Ankylosing Spondylitis (POSTURE)

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ClinicalTrials.gov Identifier: NCT01583374

Recruitment Status : Completed

First Posted : April 24, 2012

Results First Posted : March 17, 2015

Last Update Posted : May 12, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Amgen

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition	Ankylosing Spondyloarthritis
Interventions	Drug: Apremilast tablet 20 mg Drug: Apremilast tablet 30 mg BID Drug: Placebo
Enrollment	490

Participant Flow

Recruitment Details

The study enrolled participants at 88 study sites and in 18 countries (Australia, Austria, Bulgaria, Czech Republic, Estonia, France, Germany, Hungary, the Netherlands, Poland, Romania, Russia, Slovakia, Spain, the United Kingdom, Canada, Sweden, and the United States [US]).

Pre-assignment Details

Randomized participants were stratified by the following 2 parameters:

C-Reactive Protein (CRP) concentration (normal: ≤ 1.5 mg/dL or elevated: > 1.5 mg/dL) at screening;
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score < 6.0 or BASDAI score ≥ 6.0 at baseline.


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg	Placebo / Apremilast 30 mg Early Escape (EE)	Placebo/Apremilast 30 mg Crossover (XO)	Apremilast 30 mg /Apremilast 30 mg EE	Apremilast 20 mg /Apremilast 30 mg EE	Apremilast 30 mg /Apremilast 30 mg Second Escape (SE)	Apremilast 20 mg/Apremilast 30 mg SE
Arm/Group Description	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase continued to receive 20 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase, continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to receive placebo tablets BID who did not have at least 20% improvement or ≥ 1 unit improvement from baseline in 2 out of 4 of the Assessment of SpondyloArthritis International Society (ASAS) domains at Week 16 were transitioned to 30 mg apremilast tablets BID and continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to placebo tablets BID in the 24-week placebo controlled phase were transitioned to 30 mg apremilast tablets BID at Week 24 and continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase who did not have at least 20% improvement or a ≥ 1-unit improvement from baseline in 2 of the 4 ASAS domains at Week 16 continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 20 mg apremilast tablets BID who did not have at least 20% improvement or ≥ 1 unit improvement from baseline in 2 out of 4 of the ASAS domains at Week 16 were transitioned to 30 mg apremilast tablets BID and continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 30 mg apremilast tablets BID who did not have at least 20% improvement or ≥ 1 unit improvement from baseline in 2 out of 4 of the ASAS domains from baseline at Week 24 continued to receive 30 mg apremilast tablets BID (second escape) for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 20 mg apremilast tablets BID who did not have at least 20% improvement or ≥ 1 unit improvement from baseline in 2 out of 4 of the ASAS domains at Week 24 were transitioned to 30 mg apremilast tablets BID (second escape) and continued to receive 30 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.
Period Title: Placebo-controlled Phase (Week 0-24)
Started	164	163	163	0	0	0	0	0	0
Received Treatment	164	163	163	0	0	0	0	0	0
Completed Week 16	150	151	144	0	0	0	0	0	0
Early Escape at Week 16	51 ^[1]	49	49 ^[1]	0	0	0	0	0	0
Completed	145 ^[2]	147 ^[2]	138 ^[2]	0	0	0	0	0	0
Not Completed	19	16	25	0	0	0	0	0	0
Reason Not Completed
Adverse Event	6	7	12	0	0	0	0	0	0
Lack of Efficacy	3	2	5	0	0	0	0	0	0
Non-compliance with Study Drug	1	1	0	0	0	0	0	0	0
Withdrawal by Subject	8	3	5	0	0	0	0	0	0
Lost to Follow-up	1	2	0	0	0	0	0	0	0
Protocol Violation	0	0	3	0	0	0	0	0	0
Other	0	1	0	0	0	0	0	0	0
[1] One participant who escaped early did not complete Week 24 [2] Completed = participants who completed the Placebo-controlled Phase
Period Title: Extension Phase (Weeks 24 to 52)
Started ^[1]	0	74	65	47	91	48	48	25	23
Completed	0	69	61	41	85	43	43	22	21
Not Completed	0	5	4	6	6	5	5	3	2
Reason Not Completed
Lost to Follow-up	0	0	0	0	0	0	0	1	0
Adverse Event	0	1	2	0	1	1	0	1	0
Lack of Efficacy	0	2	0	6	3	2	5	1	2
Non-compliance study drug	0	2	1	0	1	0	0	0	0
Withdrawal by Subject	0	0	1	0	1	2	0	0	0
[1] 9 participants who completed Week 24 did not continue in the extension phase.
Period Title: Long-Term Extension Phase Weeks 52-260
Started ^[1]	0	66	61	35	81	39	38	21	20
Completed	0	40	41	22	50	22	20	12	10
Not Completed	0	26	20	13	31	17	18	9	10
Reason Not Completed
Adverse Event	0	5	2	2	6	2	2	3	1
Lack of Efficacy	0	4	6	7	10	7	4	2	4
Noncomplinace with Study Drug	0	0	0	0	1	0	0	1	1
Withdrawal by Subject	0	11	11	1	12	7	5	3	3
Death	0	0	0	0	1	0	1	0	0
Lost to Follow-up	0	1	0	1	1	0	1	0	0
Miscellaneous	0	5	1	2	0	1	5	0	1
[1] 24 participants who completed Week 52 did not continue in the Week 52-260 study period

Baseline Characteristics

Arm/Group Title		Placebo	Apremilast 20 mg	Apremilast 30 mg	Total
Arm/Group Description		Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...	Total of all reporting groups
Arm/Group Description		Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase continued to receive 20 mg apremilast tablets BID for up to 4.5 years in the long-term extension phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Total of all reporting groups
Overall Number of Baseline Participants		164	163	163	490
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The modified Intent to Treat (mITT) population included all participants who were randomized and received at least one dose of investigational product (IP); Five participants did not have a baseline SF-36 Physical Component Summary score.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
		44.0 (12.89)	45.2 (11.90)	44.8 (11.75)	44.7 (12.18)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
	Female	40 24.4%	42 25.8%	56 34.4%	138 28.2%
	Male	124 75.6%	121 74.2%	107 65.6%	352 71.8%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
	Hispanic or Latino	5 3.0%	1 0.6%	1 0.6%	7 1.4%
	Not Hispanic or Latino	158 96.3%	159 97.5%	162 99.4%	479 97.8%
	Unknown or Not Reported	1 0.6%	3 1.8%	0 0.0%	4 0.8%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	2 1.2%	2 1.2%	0 0.0%	4 0.8%
	Black or African American	1 0.6%	2 1.2%	2 1.2%	5 1.0%
	Native Hawaiian or Other Pacific Islander	1 0.6%	0 0.0%	0 0.0%	1 0.2%
	White	158 96.3%	154 94.5%	158 96.9%	470 95.9%
	Other	1 0.6%	2 1.2%	3 1.8%	6 1.2%
	Missing	1 0.6%	3 1.8%	0 0.0%	4 0.8%
Duration of Ankylosing Spondylitis (Lower Back Pain and Stiffness) Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
		10.40 (10.375)	11.06 (11.302)	10.32 (9.887)	10.60 (10.521)
Duration of Ankylosing Spondylitis Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
	≤ 2 years	41 25.0%	48 29.4%	40 24.5%	129 26.3%
	>2 to ≤ 5 years	29 17.7%	23 14.1%	26 16.0%	78 15.9%
	>5 to ≤ 10 years	33 20.1%	29 17.8%	33 20.2%	95 19.4%
	>10 years	61 37.2%	63 38.7%	64 39.3%	188 38.4%
Baseline Bath Ankylosing Spondylitis Functional Index (BASFI) Score (0 - 10 NRS) ^[1] Mean (Standard Deviation) Unit of measure: Units on a Scale
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
		5.76 (2.194)	5.75 (2.061)	5.65 (2.100)	5.72 (2.115)
		[1] Measure Description: The BASFI is a composite score based on a self-administered survey of 10 questions using a 0 to 10 unit numerical rating scale (NRS) that assesses the degree of mobility and functional ability. The survey consists of 8 questions regarding function in AS and the last 2 reflect the ability to manage everyday life. The patient marks a box with an X on a 0 to 10 unit NRS for 10 questions; the left-hand box of 0 = easy; the right-hand box = impossible. The resulting 0 to 100 score is divided by 10 to give a final 0 to 10 BASFI score. A higher score correlates to reduced functional ability.
Baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score (0 - 10 NRS) ^[1] Mean (Standard Deviation) Unit of measure: Units on a Scale
	Number Analyzed	164 participants	163 participants	163 participants	490 participants
		6.45 (1.319)	6.46 (1.352)	6.37 (1.357)	6.42 (1.341)
		[1] Measure Description: The BASDAI is a composite score based on a self-administered survey of 6 questions using a 0 to 10 unit NRS that assesses for 5 major symptoms of AS: fatigue; spinal pain; peripheral joint pain/swelling; areas of localized tenderness; morning stiffness severity upon wakening; morning stiffness duration upon wakening. To give each of the 5 symptoms equal weighting, the mean of the 2 scores relating to morning stiffness is taken. The resulting 0 to 50 score is divided by 5 to give a final 0 to 10 BASDAI score. A score of 4 or greater is considered to be indicative of active AS disease.
Baseline Bath Ankylosing Spondylitis Metrology Index (BASMI)-Linear Score (0 - 10 NRS) ^[1] [2] Mean (Standard Deviation) Unit of measure: Units on a Scale
	Number Analyzed	163 participants	163 participants	161 participants	487 participants
		4.36 (1.608)	4.63 (1.721)	4.41 (1.700)	4.47 (1.678)
		[1] Measure Description: The BASMI-Linearis designed to assess axial status (ie, cervical, dorsal and lumbar spine, hips, and pelvic soft tissue) and to define clinically significant changes in spinal movement. 5 dimensions of movement (lateral lumbar flexion, tragus to wall, forward lumbar flexion, maximal intermalleolar distance, and cervical rotation) were measured and normalized on 0 to 10 unit NRS. The average of these scores is the total BASMI score, with a higher value indicating more severe limitation in spinal mobility. [2] Measure Analysis Population Description: Three participants did not have baseline BASMI data.
Baseline Ankylosing Spondylitis Quality of Life (ASQoL) Summary Score (0-18) ^[1] [2] Mean (Standard Deviation) Unit of measure: Units on a Scale
	Number Analyzed	164 participants	162 participants	160 participants	486 participants
		9.10 (4.639)	8.38 (4.548)	8.62 (4.935)	8.50 (4.738)
		[1] Measure Description: The ASQoL is a validated disease specific patient reported outcomes instrument to assess the impact of ankylosing spondylitis on the QoL of individuals with emphasis on the ability of the person to fulfill his or her needs. It consisted of 18 items requesting a yes (score=1) or no (score=0) response to questions related to the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. The summary score ranges 0-18 with higher scores indicating worse quality of life. [2] Measure Analysis Population Description: Four participants did not have a baseline ASQoL score.
Baseline Physical Component Summary Score of Medical Outcome Study Short Form 36-Item Survey ^[1] [2] Mean (Standard Deviation) Unit of measure: Units on a Scale
	Number Analyzed	164 participants	162 participants	159 participants	485 participants
		32.57 (7.821)	31.89 (8.561)	32.16 (8.846)	32.20 (8.402)
		[1] Measure Description: The SF- 36 is a self-administered instrument that measures the impact of disease and consists of 36 questions in 8 domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Two overall summary scores can also be obtained-a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). The PCS and MCS scores are transformed to have a mean of 50 and standard deviation of 10, with higher scores indicating better health. Scale scores range from 0 to 100, with higher scores indicating better health. [2] Measure Analysis Population Description: Five participants did not have a baseline SF-36 Physical Component Summary score.

Outcome Measures

1.Primary Outcome


Title	Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) Response at Week 16
Description	ASAS 20 was defined as achieving an improvement from baseline of Ͱ...
Description	ASAS 20 was defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are: Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = "no pain" and the right-hand box = "most severe pain" Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)
Time Frame	Baseline and Week 16

Outcome Measure Data

Analysis Population Description

The mITT population included participants who were randomized and received at least one dose of investigation product (IP). Participants who discontinued early due to lack of efficacy were counted as nonresponders, and last observation carried forward (LOCF) imputation was used for participants who discontinued for other reasons.


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	164	163	163
Measure Type: Number Unit of Measure: Percentage of Participants
	36.6	35.0	32.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4383
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	2 sided p-value was based on CMH test adjusting for C-reactive protein (CRP) category and baseline BASDAI score category

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95% -14.3 to 6.2
	Estimation Comments	Adjusted difference is the weighted average of the treatment differences across the 4 strata of screening CRP category and baseline BASDAI score category with the Cochran-Mantel-Haenszel (CMH) weights

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7427
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	2 sided p-value was based on CMH test adjusting for C-reactive protein (CRP) category and baseline BASDAI score category

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-1.7
	Confidence Interval	(2-Sided) 95% -12.0 to 8.5
	Estimation Comments	Adjusted difference in proportions is the weighted average of the treatment differences across the 4 strata of screening CRP category and baseline BASDAI score category with the Cochran-Mantel-Haenszel weights.

2.Secondary Outcome


Title	Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 24
Description	The BASFI is a composite score based on a self-administered survey of ...
Description	The BASFI is a composite score based on a self-administered survey of 10 questions using a 0 to 10 unit numerical rating scale (NRS) that assesses the degree of mobility and functional ability. The survey consists of 8 questions regarding function in AS and the last 2 reflect the ability to manage everyday life. The patient marks a box with an X on a 0 to 10 unit NRS for 10 questions; the left-hand box of 0 = easy; the right-hand box = impossible. The resulting 0 to 100 score is divided by 10 to give a final 0 to 10 BASFI score. The overall score is the mean of the 10 items and ranges from 0 to 10. A higher score correlates to reduced functional ability.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The mITT population included those who were randomized and received at least one dose of IP. Missing data were imputed as baseline carried forward for participants who escaped early or discontinued early (prior to Week 24) due to lack of efficacy and LOCF for other early discontinuations


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	162	163	160
Least Squares Mean (Standard Error) Unit of Measure: Units on a Scale
	-0.94 (0.136)	-1.11 (0.137)	-0.99 (0.138)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8032
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95% -0.41 to 0.32
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3624
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95% -0.53 to 0.19
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
Description	The BASDAI is a composite score based on a participant self-administer...
Description	The BASDAI is a composite score based on a participant self-administered survey of six questions measured using a 0 to 10 unit numerical rating scale (NRS) that assessed the participants' five major symptoms of AS: 1) fatigue; 2) spinal pain; 3) peripheral joint pain/swelling; 4) areas of localized tenderness; 5a) morning stiffness severity upon wakening; 5b) morning stiffness duration upon wakening. The participant was asked to mark the box with an X on a 0 to 10 unit NRS for each of the 6 questions. To give each of the five symptoms equal weighting, the mean of the two scores relating to morning stiffness was taken. The resulting 0 to 50 score was divided by 5 to give a final 0 to 10 BASDAI score. A BASDAI score of 4 or greater was considered to be indicative of active AS disease.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	164	162	160
Least Squares Mean (Standard Error) Unit of Measure: Units on a Scale
	-1.21 (0.136)	-1.30 (0.136)	-1.18 (0.137)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.8618
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95% -0.33 to 0.40
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6262
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95% -0.45 to 0.27
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS) Response at Week 24
Description	ASAS 20 was defined as achieving an improvement from baseline of Ͱ...
Description	ASAS 20 was defined as achieving an improvement from baseline of ≥ 20% and ≥ 1 unit in at least 3 of 4 ASAS domains on a scale of 0 to 10 units and no worsening from baseline of ≥ 20% and ≥ 1 unit in the remaining ASAS domain on a scale of 0 to 10 units. The 4 ASAS domains are: Patient Global Assessment of Disease (0 - 10 unit Numerical Rating Scale [NRS]); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = not active and the right-hand box = very active Total Back Pain (0 to 10 unit NRS); participant marks a box with an X on a 0 - 10 unit NRS; the left-hand box of 0 = "no pain" and the right-hand box = "most severe pain" Function (Bath AS Functional Index [BASFI] NRS 0 - 10 unit); participant provides a self-administered survey of 10 questions assessing for degree of mobility and functional ability Inflammation domain is determined by the mean of 2 Bath AS Disease Activity Index NRS Questions #5 and #6 for morning stiffness) (0 - 10 unit)
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	164	163	163
Measure Type: Number Unit of Measure: Percentage of Participants
	31.7	36.2	33.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6958
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	2 sided p-value was based on the CMH test adjusting for C-reactive protein (CRP) category and baseline BASDAI score category.

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95% -8.1 to 12.2
	Estimation Comments	Adjusted difference is the weighted average of the treatment differences across the 4 strata of screening CRP category and baseline BASDAI score category with the Cochran-Mantel-Haenszel weights.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4051
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	2 sided p-value was based on the CMH test adjusting for C-reactive protein (CRP) category and baseline BASDAI score category.

Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.4
	Confidence Interval	(2-Sided) 95% -5.8 to 14.5
	Estimation Comments	Adjusted difference is the weighted average of the treatment differences across the 4 strata of screening CRP category and baseline BASDAI score category with the Cochran-Mantel-Haenszel weights.

5.Secondary Outcome


Title	Change From Baseline in the Ankylosing Spondylitis Quality of Life (ASQoL) Summary Score at Week 24
Description	The ASQoL is a validated disease specific patient reported outcomes in...
Description	The ASQoL is a validated disease specific patient reported outcomes instrument to assess the impact of ankylosing spondylitis on the quality of life of individuals with emphasis on the ability of the person to fulfill his or her needs. It consisted of 18 items requesting a yes (score=1) or no (score=0) response to questions related to the impact of pain on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. The summary score ranges 0-18 with higher scores indicating worse quality of life.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

The mITT included those who were randomized and received at least one dose of IP. Missing data were imputed as baseline carried forward for participants who escaped early or discontinued early (prior to Week 24) due to lack of efficacy and LOCF for other early discontinuations.


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	160	161	156
Least Squares Mean (Standard Error) Unit of Measure: Units on a Scale
	-1.77 (0.278)	-1.50 (0.278)	-1.52 (0.281)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5126
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.25
	Confidence Interval	(2-Sided) 95% -0.49 to 0.99
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.4624
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95% -0.46 to 1.01
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Change From Baseline in the Physical Component Summary Score (PCS) of Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) at Week 24
Description	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 ...
Description	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) was 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 (based on US general population with mean of 50 and standard deviation of 10) were used in analyses. Higher scores indicate a higher level of functioning. The PCS encompasses physical functioning, role-physical, and bodily pain, as well as general health and vitality. A positive change from baseline score indicates an improvement
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	160	161	155
Least Squares Mean (Standard Error) Unit of Measure: Units on a Scale
	3.50 (0.553)	3.46 (0.551)	3.79 (0.559)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.6997
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95% -1.18 to 1.76
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.9587
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95% -1.50 to 1.42
	Estimation Comments	[Not Specified]

7.Secondary Outcome


Title	Change From Baseline in Bath Ankylosing Spondylitis Metrology Index-Linear (BASMI-Linear) at Week 24
Description	The BASMI-Linear was designed to assess axial status (ie, cervical, do...
Description	The BASMI-Linear was designed to assess axial status (ie, cervical, dorsal and lumbar spine, hips, and pelvic soft tissue) and to define clinically significant changes in spinal movement. Five dimensions of movement (lateral lumbar flexion, tragus to wall, forward lumbar flexion, maximal intermalleolar distance, and cervical rotation) were measured and normalized on 0 to 10 unit NRS. The average of these scores was the total BASMI score, ranging from 0-10 with higher values indicating more severe limitation in spinal mobility.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	163	162	158
Least Squares Mean (Standard Error) Unit of Measure: Units on a Scale
	-0.19 (0.042)	-0.16 (0.043)	-0.13 (0.043)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 30 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.3307
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95% -0.06 to 0.17
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Apremilast 20 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5938
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Based on an ANCOVA model for change from baseline with treatment group, CRP and baseline BASDAI score as factors and baseline value as covariate.

Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95% -0.08 to 0.14
	Estimation Comments	[Not Specified]

8.Secondary Outcome


Title	Change From Baseline in the Radiographic Score Using the Modified Stoke Ankylosing Spondylitis Spine Score (m-SASSS) at Week 104 and Week 260
Description	The Modified Stoke Ankylosing Spondylitis Spine Score is a scoring met...
Description	The Modified Stoke Ankylosing Spondylitis Spine Score is a scoring method used to determine the amount or degree of ankylosing spondylitis disease that is in the spine based on x-ray radiographs of the spine. The m-SASSS scores 0-3. 0 = No abnormality, 1 = Erosion, Sclerosis or Squaring, 2 = Syndesmophyte, 3 = Total bony Bridging at each Site. An increase in the m-SASSS indicated a worsening of AS disease.
Time Frame	Baseline to Week 104 and 260

Outcome Measure Data

Analysis Population Description

The radiograph subset analysis population included randomized participants who received at least one dose of IP and had at least a baseline radiograph available. Includes apremilast participants as treated who had a baseline and at least one post-baseline score. Missing scores were imputed using the LOCF.


Arm/Group Title		Apremilast 20 mg	Apremilast 30 mg	Placebo/Apremilast 30 mg	Apremilast 20 mg/ Apremilast 30 mg	Apremilast 20 mg/Apremilast 20 mg
Arm/Group Description:		Participants initially randomized t...	Participants initially randomized a...	Participants who initially received...	Participants who were initially ran...	Participants who were initially ran...
Arm/Group Description:		Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase, and continued to receive apremilast 20 mg or 30 mg during weeks 24 to 260.	Participants initially randomized at Week 0 to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase, and continued to receive apremilast 30 mg during weeks 24 to 260.	Participants who initially received placebo tablets BID during the placebo controlled phase were transitioned to 30 mg apremilast tablets BID either at Week 16 or Week 24 through to Week 260.	Participants who were initially randomized to 20 mg apremilast tablets BID at Week 0 and transitioned to 30 mg apremilast tablets BID at either Week 16 or Week 24 through to Week 260.	Participants who were initially randomized to receive 20 mg apremilast PO BID at Week 0 and continued to receive 20 mg apremilast PO BID through to Week 260 without the transition to 30 mg apremilast PO BID.
Overall Number of Participants Analyzed		83	84	79	35	48
Mean (Standard Deviation) Unit of Measure: Units on a Scale
Week 104	Number Analyzed	81 participants	81 participants	74 participants	35 participants	46 participants
Week 104		0.99 (3.018)	0.65 (2.453)	0.98 (3.768)	0.82 (2.435)	1.12 (3.417)
Week 260	Number Analyzed	83 participants	84 participants	79 participants	35 participants	48 participants
Week 260		3.14 (8.292)	1.79 (6.997)	1.92 (7.363)	2.21 (5.959)	3.83 (9.652)

9.Secondary Outcome


Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Placebo Controlled Phase
Description	A TEAE was an adverse event (AE) with a start date on or after the dat...
Description	A TEAE was an adverse event (AE) with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. A serious AE = results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; or constitutes an important medical event. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = symptoms causing severe pain discomfort.
Time Frame	From Week 0 to Week 24; the median duration of exposure was 23.57 weeks for the placebo arm, 23.71 weeks for the apremilast 20 mg arm and 24.00 weeks for the apremilast 30 mg arm.

Outcome Measure Data

Analysis Population Description

Safety population includes all participants who were randomized and received at least one dose of IP. Includes data through Week 16 for placebo-treated and apremilast 20 mg BID treated participants who escaped early and data up to Week 24 for all other participants.


Arm/Group Title	Placebo	Apremilast 20 mg	Apremilast 30 mg
Arm/Group Description:	Participants initially randomized t...	Participants initially randomized t...	Participants initially randomized t...
Arm/Group Description:	Participants initially randomized to receive placebo tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.
Overall Number of Participants Analyzed	164	163	163
Measure Type: Count of Participants Unit of Measure: Participants
Any Treatment Emergent Adverse Event	83 50.6%	91 55.8%	88 54.0%
Any Drug-related TEAE	24 14.6%	44 27.0%	51 31.3%
Any Severe TEAE	0 0.0%	2 1.2%	5 3.1%
Any Serious TEAE	1 0.6%	3 1.8%	6 3.7%
Any Serious Drug-related TEAE	0 0.0%	0 0.0%	3 1.8%
Any TEAE Leading to Drug Interruption	14 8.5%	13 8.0%	14 8.6%
Any TEAE Leading to Drug Withdrawal	7 4.3%	11 6.7%	13 8.0%
Any TEAE Leading to Death	0 0.0%	0 0.0%	0 0.0%

10.Secondary Outcome


Title	Number of Participants With Treatment Emergent Adverse Events During the Apremilast Exposure Period
Description	A TEAE was an adverse event (AE) with a start date on or after the dat...
Description	A TEAE was an adverse event (AE) with a start date on or after the date of the first dose of IP and no later than 28 days after the last dose of IP for participants who discontinued early. A serious AE = results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; or constitutes an important medical event. The severity of AEs was assessed based on the following scale: Mild = asymptomatic or mild symptoms, clinical or diagnostic observations only; Moderate = symptoms cause moderate discomfort; Severe = symptoms causing severe pain discomfort.
Time Frame	Week 0 to week 260; overall mean duration of exposure to apremilast 20 mg and 30 mg BID was 160.96 weeks

Outcome Measure Data

Analysis Population Description

Apremilast Subjects as Treated (AAT) were those who received at least 1 dose of apremilast at any time during the study. Participants were included in the treatment group corresponding to the apremilast dosing regimen they actually received, irrespective of the treatment group to which they were randomized or re-randomized.


Arm/Group Title	Apremilast 20 mg	Apremilast 20/30 mg	Apremilast 30 mg
Arm/Group Description:	Participants who received 20 mg apr...	Participants who initially received...	Participants initially randomized t...
Arm/Group Description:	Participants who received 20 mg apremilast tablets BID only in the study. This also includes participants who initially received APR 20 BID and switched to APR 30 BID treatment. Only the TEAEs that occurred during the 20 mg apremilast BID dose were included.	Participants who initially received 20 mg apremilast tablets BID at Week 0 who escaped to 30 mg apremilast BID. Only the TEAEs that occurred during the apremilast 30 mg BID dose were included.	Participants initially randomized to 30 mg apremilast tablets BID at Week 0 and participants who received placebo at Week 0 who escaped to 30 mg apremilast BID. Only the TEAEs that occurred during the APR 30 mg BID dose were included.
Overall Number of Participants Analyzed	163	72	305
Measure Type: Count of Participants Unit of Measure: Participants
Any Treatment Emergent Adverse Event	114 69.9%	47 65.3%	239 78.4%
Any Severe TEAE	5 3.1%	8 11.1%	23 7.5%
Any Serious TEAE	12 7.4%	8 11.1%	41 13.4%
Any TEAE Leading to Drug Interruption	22 13.5%	11 15.3%	51 16.7%
Any TEAE Leading to Drug Withdrawal	18 11.0%	4 5.6%	34 11.1%
Any TEAE Leading to Death	0 0.0%	1 1.4%	1 0.3%

Adverse Events

Time Frame	AEs were reported for the placebo-controlled phase from Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants. AEs were reported for the apremilast (APR) exposure period from Week 0 to Week 260, irrespective of when the APR started (Week 0, 16 or 24). The median duration of treatment was 24, 163, and 216 weeks in the Apremilast 20 mg, Apremilast 20/30 mg and Apremilast 30 mg treatment groups respectively.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Placebo (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 30 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (APR Exposure Period)	Apremilast 20/30 mg BID (APR Exposure Period)	Apremilast 30 mg BID (APR Exposure Period)
Arm/Group Description	Participants randomized to placebo ...	Participants initially randomized t...	Participants initially randomized t...	Participants who received 20 mg apr...	Participants who initially received...	Participants initially randomized t...
Arm/Group Description	Participants randomized to placebo tablets twice daily (BID) in the 24-week placebo-controlled phase.	Participants initially randomized to 20 mg apremilast tablets (APR) BID in the 24-week placebo-controlled phase.	Participants initially randomized to 30 mg apremilast tablets BID in the 24-week placebo-controlled phase.	Participants who received 20 mg apremilast tablets BID only in the study. This also includes participants who initially received APR 20 BID and switched to APR 30 BID treatment. Only the TEAEs that occurred during the 20 mg apremilast BID dose were included.	Participants who initially received 20 mg apremilast tablets BID at Week 0 who escaped to 30 mg apremilast BID. Only the TEAEs that occurred during the 20 mg apremilast BID dose were included.	Participants initially randomized to 30 mg apremilast tablets BID at Week 0 and participants who received placebo at Week 0 who escaped to 30 mg apremilast tablets BID. Only the TEAEs that occurred during the 30 mg apremilast BID dose were included.
All-Cause Mortality
	Placebo (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 30 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (APR Exposure Period)	Apremilast 20/30 mg BID (APR Exposure Period)	Apremilast 30 mg BID (APR Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	1/305 (0.33%)
Serious Adverse Events Serious Adverse Events
	Placebo (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 30 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (APR Exposure Period)	Apremilast 20/30 mg BID (APR Exposure Period)	Apremilast 30 mg BID (APR Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/164 (0.61%)	3/163 (1.84%)	6/163 (3.68%)	12/163 (7.36%)	8/72 (11.11%)	41/305 (13.44%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Cardiac disorders
Cardiomyopathy ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Coronary artery disease ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Sick sinus syndrome ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Acute myocardial infarction ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	1/305 (0.33%)
Atrial fibrillation ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	1/72 (1.39%)	1/305 (0.33%)
Atrial tachycardia ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Cardio-respiratory arrest ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Ear and labyrinth disorders
Vertigo ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	1/72 (1.39%)	1/305 (0.33%)
Endocrine disorders
Goitre ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Eye disorders
Iridocyclitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	1/305 (0.33%)
Retinal vein occlusion ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Strabismus ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Uveitis ^† 1	0/164 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	2/305 (0.66%)
Gastrointestinal disorders
Abdominal hernia ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Abdominal pain ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Abdominal pain upper ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Anal fissure ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Diverticulum intestinal ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Duodenogastric reflux ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Inguinal hernia ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Jejunal perforation ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Pancreatitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Small intestinal obstruction ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Umbilical hernia ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Vomiting ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
General disorders
Chest pain ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Device failure ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Pyrexia ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Hepatobiliary disorders
Alcoholic liver disease ^† 1	0/164 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Cholelithiasis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Gallbladder polyp ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Infections and infestations
Appendicitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Bronchitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Chronic sinusitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Infected bites ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Peritonsillar abscess ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Injury, poisoning and procedural complications
Cardiac function disturbance postoperative ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Foot fracture ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Humerus fracture ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Lower limb fracture ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Pneumothorax traumatic ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Tibia fracture ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Musculoskeletal and connective tissue disorders
Ankylosing spondylitis ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Cervical spinal stenosis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Intervertebral disc protrusion ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Muscular weakness ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Musculoskeletal chest pain ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Osteoarthritis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	1/72 (1.39%)	1/305 (0.33%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	1/305 (0.33%)
Breast cancer in situ ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Malignant melanoma ^† 1	1/164 (0.61%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	0/305 (0.00%)
Prostate cancer ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Rectal cancer ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	1/305 (0.33%)
Uterine leiomyoma ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	1/305 (0.33%)
Nervous system disorders
Ischaemic stroke ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Presyncope ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Thrombotic cerebral infarction ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Transient ischaemic attack ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
VIIth nerve paralysis ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Vertebrobasilar insufficiency ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Psychiatric disorders
Depression ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Major depression ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Suicide attempt ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	1/305 (0.33%)
Renal and urinary disorders
Calculus ureteric ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	2/305 (0.66%)
Calculus urinary ^† 1	0/164 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Renal colic ^† 1	0/164 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Respiratory, thoracic and mediastinal disorders
Lung disorder ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	0/72 (0.00%)	0/305 (0.00%)
Lung infiltration ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Nasal septum deviation ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Nasal turbinate hypertrophy ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
Pulmonary embolism ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	1/72 (1.39%)	0/305 (0.00%)
Respiratory failure ^† 1	0/164 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/163 (0.00%)	0/72 (0.00%)	1/305 (0.33%)
1 Term from vocabulary, MedDRA 14.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 30 mg BID (Weeks 0-24) Placebo-Controlled Phase	Apremilast 20 mg BID (APR Exposure Period)	Apremilast 20/30 mg BID (APR Exposure Period)	Apremilast 30 mg BID (APR Exposure Period)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	37/164 (22.56%)	58/163 (35.58%)	57/163 (34.97%)	82/163 (50.31%)	38/72 (52.78%)	168/305 (55.08%)
Eye disorders
Iridocyclitis ^† 1	0/164 (0.00%)	1/163 (0.61%)	1/163 (0.61%)	2/163 (1.23%)	4/72 (5.56%)	8/305 (2.62%)
Gastrointestinal disorders
Abdominal pain upper ^† 1	4/164 (2.44%)	3/163 (1.84%)	9/163 (5.52%)	7/163 (4.29%)	1/72 (1.39%)	16/305 (5.25%)
Diarrhoea ^† 1	7/164 (4.27%)	22/163 (13.50%)	17/163 (10.43%)	26/163 (15.95%)	4/72 (5.56%)	38/305 (12.46%)
Frequent bowel movements ^† 1	2/164 (1.22%)	2/163 (1.23%)	3/163 (1.84%)	3/163 (1.84%)	4/72 (5.56%)	3/305 (0.98%)
Nausea ^† 1	7/164 (4.27%)	10/163 (6.13%)	14/163 (8.59%)	13/163 (7.98%)	6/72 (8.33%)	28/305 (9.18%)
Infections and infestations
Bronchitis ^† 1	1/164 (0.61%)	4/163 (2.45%)	2/163 (1.23%)	8/163 (4.91%)	6/72 (8.33%)	10/305 (3.28%)
Nasopharyngitis ^† 1	6/164 (3.66%)	9/163 (5.52%)	7/163 (4.29%)	25/163 (15.34%)	10/72 (13.89%)	55/305 (18.03%)
Sinusitis ^† 1	1/164 (0.61%)	2/163 (1.23%)	1/163 (0.61%)	7/163 (4.29%)	5/72 (6.94%)	10/305 (3.28%)
Upper respiratory tract infection ^† 1	8/164 (4.88%)	7/163 (4.29%)	8/163 (4.91%)	17/163 (10.43%)	8/72 (11.11%)	32/305 (10.49%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	0/164 (0.00%)	2/163 (1.23%)	1/163 (0.61%)	6/163 (3.68%)	4/72 (5.56%)	12/305 (3.93%)
Muscle spasms ^† 1	1/164 (0.61%)	4/163 (2.45%)	0/163 (0.00%)	5/163 (3.07%)	4/72 (5.56%)	4/305 (1.31%)
Musculoskeletal pain ^† 1	0/164 (0.00%)	0/163 (0.00%)	1/163 (0.61%)	2/163 (1.23%)	4/72 (5.56%)	3/305 (0.98%)
Osteoarthritis ^† 1	0/164 (0.00%)	1/163 (0.61%)	0/163 (0.00%)	2/163 (1.23%)	4/72 (5.56%)	5/305 (1.64%)
Nervous system disorders
Headache ^† 1	8/164 (4.88%)	9/163 (5.52%)	16/163 (9.82%)	11/163 (6.75%)	5/72 (6.94%)	28/305 (9.18%)
Vascular disorders
Hypertension ^† 1	4/164 (2.44%)	4/163 (2.45%)	6/163 (3.68%)	6/163 (3.68%)	2/72 (2.78%)	21/305 (6.89%)
1 Term from vocabulary, MedDRA 14.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation generally sixty (60) days in advance of the submission, (ii) delete any confidential information of the sponsor, and (iii) delay submission for generally up to ninety (90) days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.

Results Point of Contact

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Name/Title:	Anne McClain, Senior Study Manager
Organization:	Celgene Corporation
Phone:	888-260-1599
EMail:	ClinicalTrialDisclosure@Celgene.com

Publications:

Gladman DD, Kavanaugh A, Gomez-Reino JJ, Wollenhaupt J, Cutolo M, Schett G, Lespessailles E, Guerette B, Delev N, Teng L, Edwards CJ, Birbara CA, Mease PJ. Therapeutic benefit of apremilast on enthesitis and dactylitis in patients with psoriatic arthritis: a pooled analysis of the PALACE 1-3 studies. RMD Open. 2018 Jun 27;4(1):e000669. doi: 10.1136/rmdopen-2018-000669. eCollection 2018.

Kavanaugh A, Gladman DD, Edwards CJ, Schett G, Guerette B, Delev N, Teng L, Paris M, Mease PJ. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res Ther. 2019 May 10;21(1):118. doi: 10.1186/s13075-019-1901-3.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Taylor PC, van der Heijde D, Landewe R, McCue S, Cheng S, Boonen A. A Phase III Randomized Study of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, for Active Ankylosing Spondylitis. J Rheumatol. 2021 Aug;48(8):1259-1267. doi: 10.3899/jrheum.201088. Epub 2021 Feb 15.

Layout table for additonal information

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01583374
Other Study ID Numbers:	CC-10004-AS-001 2011-001555-37 ( EudraCT Number )
First Submitted:	April 20, 2012
First Posted:	April 24, 2012
Results First Submitted:	February 24, 2015
Results First Posted:	March 17, 2015
Last Update Posted:	May 12, 2020

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