Clinical Trial Results:
A Multi-Center, Open-Label Efficacy, Safety, and Pharmacokinetic Study of Adalimumab in Japanese Subjects with Active Ankylosing Spondylitis
Summary
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EudraCT number |
2014-004532-18 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 Jan 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Apr 2016
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First version publication date |
13 Jun 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M10-239
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00667355 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AbbVie
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Sponsor organisation address |
1 North Waukegan Road, North Chicago, IL, United States, 60064
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Public contact |
Global Medical Information, AbbVie, 001 800-633-9110,
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Scientific contact |
Hideyuki Hashiba, AbbVie, Hideyuki.Hashiba@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Jan 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jan 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate efficacy, safety and pharmacokinetics of adalimumab in Japanese subjects with active ankylosing spondylitis
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Protection of trial subjects |
Subject and/or legal guardian read and understood information provided about the study and gave written permission.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Mar 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 41
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Worldwide total number of subjects |
41
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
39
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
Pre-assignment
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Screening details |
The study included a 2-week screening period. | ||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Adalimumab | ||||||||||||||
Arm description |
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
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Other name |
ABT-D2E7, Humira
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
40 mg or 80 mg every other week, subcutaneous
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Baseline characteristics reporting groups
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Reporting group title |
Adalimumab
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Reporting group description |
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adalimumab
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Reporting group description |
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan. |
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End point title |
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 20 (ASAS 20) at Week 12 [1] | ||||||||||||||
End point description |
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = at least 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0 - 100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. For all non-responder imputation (NRI) analyses, subjects with a missing value at a visit were imputed as a non-responder for that visit. Observed cases is based on a total of 40 subjects analyzed (vs. 41 subjects for the study and all other analysis sets) due to 1 subject who discontinued prior to Week 12.
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End point type |
Primary
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End point timeframe |
Week 12
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were summarize for this end point per protocol. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving ASAS 20 | ||||||||||||||||||||||
End point description |
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute improvement ≥ 10 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. Analysis is based on non-responder imputation (NRI), for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving ASAS 50 | ||||||||||||||||||||||
End point description |
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = at least 50% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving ASAS 70 | ||||||||||||||||||||||
End point description |
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS has 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = at least 70% improvement (vs. baseline) and an absolute improvement ≥ 30 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening (defined as a worsening of ≥ 20% and a net worsening of ≥ 10 units) in the remaining domain. Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) | ||||||||||||||||||||||
End point description |
BASDAI is a validated self assessment tool used to determine disease activity in subjects with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) subjects answered 6 questions measuring discomfort, pain, fatigue, and morning stiffness. BASDAI 50 = at least 50% improvement (vs. baseline) in BASDAI. Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Patient's Global Assessment of Disease Activity | ||||||||||||||||||||||
End point description |
Subject's assessment of disease activity using a Visual Analog Scale (VAS) of 0 – 100 mm (0 = none and 100 = severe). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Total Back Pain | ||||||||||||||||||||||
End point description |
Subject assessed his/her back pain by using a Visual Analog Scale (VAS) of 0 – 100 mm (0 = no pain and 100 = most severe pain). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | ||||||||||||||||||||||
End point description |
BASFI is a validated self assessment tool that determines the degree of functional limitation in AS subjects. Utilizing a VAS of 0–100 mm (0=easy, 100=impossible), subjects answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions. Analysis is based on last observation carried forward (LOCF).
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in C-Reactive Protein (CRP) | ||||||||||||||||||||||
End point description |
CRP is a marker of inflammation and measured in mg/dL. A higher level is consistent with inflammation. Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6. | ||||||||||||||||||||||
End point description |
ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (patient global assessment of disease activity, pain, function, inflammation) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains (each domain measured on a 0 - 100 scale [0 = no disease activity; 100 = high disease activity]). Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving Assessment in Ankylosing Spondylitis 40 (ASAS 40) | ||||||||||||||||||||||
End point description |
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) subjects. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 40 = at least 40% improvement (vs. baseline) and an absolute improvement ≥ 20 units on a 0-100 scale (0 = no disease activity; 100 = high disease activity) for ≥ 3 domains, and no worsening in remaining domain. Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Number of Subjects Achieving Assessment in Ankylosing Spondylitis Partial Remission | ||||||||||||||||||||||
End point description |
Partial remission is defined as a score of less than 20 units (on a scale of 0–100; 0=no disease activity and 100=high disease activity) in each of the 4 Assessments in Ankylosing Spondylitis (ASAS) domains: patient global assessment of disease activity, pain, function, and inflammation. Analysis is based on NRI, for which subjects with a missing value at a visit were imputed as a non-responder for that visit.
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End point type |
Secondary
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End point timeframe |
Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) | ||||||||||||||||||||||
End point description |
BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: tragus to wall distance, lumbar flexion, cervical rotation, lumbar side flexion, and intermalleolar distance. Each measure was scored 0-2 (0=normal mobility/mild disease involvement, 1=moderate disease involvement, 2=severe disease involvement) to give a final total score ranging from 0 to 10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS. Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Chest Expansion | ||||||||||||||||||||||
End point description |
Chest expansion is the difference in centimeters between full expiration and full inspiration, measured at the 4th inter-costal space. An increase in chest expansion represents improvement. Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) | ||||||||||||||||||||||
End point description |
Assessment of enthesitis was performed in the following 7 domains: 1) 1st costochondral joint left and right, 2) 7th costochondral joint left and right, 3) posterior superior iliac spine left and right, 4) anterior superior iliac spine left and right, 5) iliac crest left and right, 6) 5th lumbar spinous process and 7) proximal insertion of Achilles tendon left and right. Each domain was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Nocturnal Pain | ||||||||||||||||||||||
End point description |
Nocturnal pain assessed by subjects using a Visual Analog Scale (VAS) of 0 – 100 mm (0 = no pain and 100 = worst possible pain). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Swollen Joint Count for 44 Joints (SJC 44) | ||||||||||||||||||||||
End point description |
The number of swollen joints among 22 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a swollen joint was scored as 1 and absence as 0. The total SJC was derived by the sum of the scores for a range of SJC from 0 (best possible score; no swollen joints) to 44 (worse possible score; all joints swollen). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in Tender Joint Count for 46 Joints (TJC 46) | ||||||||||||||||||||||
End point description |
The number of tender or painful joints among 23 anatomical joints for both the right and left side of the body were assessed by a joint evaluator where the presence of a tender or painful joint was scored as 1 and absence as 0. The total TJC was derived by the sum of the scores for a range of TJC from 0 (best possible score; no tender or painful joints) to 46 (worst possible score; all joints tender or painful). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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End point title |
Mean Change from Baseline in 36-Item Short Form (SF-36) Questionnaire | ||||||||||||||||||||||||||||||||||||
End point description |
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These are summarized in a physical component summary (PCS) and mental component summary (MCS) score. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=lowest level of functioning; 100=highest level of functioning). Analysis is based on LOCF.
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End point type |
Secondary
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End point timeframe |
Baseline, Weeks 12, 24, 48, 72, 96, 120, and Final Visit
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All adverse events reported from the time of first study drug administration until 70 days following discontinuation of study drug administration were collected.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
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Reporting groups
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Reporting group title |
Adalimumab
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Reporting group description |
Adalimumab 40 mg or 80 mg subcutaneously administered every other week until approval of adalimumab for Ankylosing Spondylitis (AS) in Japan. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Feb 2008 |
Added the maximal limited dose of codeine phosphate and dihydrocodeine phosphate for antitussive (prohibited medications); added transdermal NSAIDs preparation to the list of restricted therapy |
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19 Mar 2008 |
Added the procedure to confirm the reason in the case when a subject was not able to receive the maximal recommended dose of NSAIDs. |
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02 Apr 2009 |
Changed the procedure for protocol deviation and protocol change due to the change of GCP. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |