Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01583374
Recruitment Status : Completed
First Posted : April 24, 2012
Results First Posted : March 17, 2015
Last Update Posted : May 12, 2020
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
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:

  1. C-Reactive Protein (CRP) concentration (normal: ≤ 1.5 mg/dL or elevated: > 1.5 mg/dL) at screening;
  2. 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
Hide 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
Arm/Group Title Placebo Apremilast 20 mg Apremilast 30 mg Total
Hide 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
Hide 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.
1.Primary Outcome
Title Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society 20 (ASAS 20) Response at Week 16
Hide 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:

  1. 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
  2. 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"
  3. 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
  4. 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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:

  1. 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
  2. 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"
  3. 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
  4. 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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.
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
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
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
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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%
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)
Hide 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%) 
Hide 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
Hide 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
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
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Study Manager
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: ClinicalTrialDisclosure@Celgene.com
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