Long-term Treatment Study of Certolizumab Pegol Without Coadministration of Methotrexate in Japanese Rheumatoid Arthritis (RA) Patients
Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT00850343
Collaborator
UCB Japan Co. Ltd. (Industry)
208
8
2
50
26
0.5
Study Details
Study Description
Brief Summary
The objectives of this study are to evaluate the safety and efficacy of certolizumab pegol when administered without coadministration of methotrexate over the long term in Japanese RA patients who transferred from Study 275-08-003 (NCT00791921), and to evaluate the effects of different dosing regimens on the safety and efficacy of certolizumab pegol in American College of Rheumatology 20% (ACR20) responders who completed Study 275-08-003.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study was initiated by Otsuka Pharmaceutical Co., Ltd and transferred to Astellas on 12/04/2012.
Study Design
Study Type:
Interventional
Actual Enrollment
:
208 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Open-label, Long-term Safety Study of CDP870 to Evaluate the Safety and Efficacy of CDP870 Administered Without Coadministration of Methotrexate (MTX) Over the Long Term in Patients With Active Rheumatoid Arthritis Transferred From the Efficacy Confirmatory Study (Study 275-08-003)
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
May 1, 2013
Actual Study Completion Date
:
May 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Certolizumab pegol 200 mg Participants received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
Drug: Certolizumab pegol
Subcutaneous (SC) injection
Other Names:
|
| Experimental: Certolizumab pegol 400 mg Participants received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
Drug: Certolizumab pegol
Subcutaneous (SC) injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events [From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks.]
An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which did not necessarily have a causal relationship with the treatment. In this study, events that occurred between the time of informed consent and the start of study medication were included in the adverse events for Study 275-08-003. Any event existing prior to the initiation of study treatment that was aggravated after initiation of study treatment was handled as a new event. The investigator assessed the severity of each AE as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A serious adverse event is an AE that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect.
Secondary Outcome Measures
- Percentage of Participants With American College of Rheumatology 20% (ACR20) Response [Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)]
A participant was an ACR20 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP).
- Percentage of Participants With American College of Rheumatology 50% (ACR50) Response [Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)]
A participant was an ACR50 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP).
- Percentage of Participants With American College of Rheumatology 70% (ACR70) Response [Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)]
A participant was an ACR70 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP).
- Change From Baseline in Disease Activity Score (DAS) 28 [Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks)]
The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count; 28 swollen joint count; Erythrocyte sedimentation rate (ESR); Patient's global assessment of disease activity. To obtain the tender joint count and swollen joint count, 28 joints of the shoulder, elbow, wrist, metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, and knee joints were examined. The data before study drug administration of 275-08-003 Study was utilized for Baseline. DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 or less indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.
- Change From Baseline in Modified Total Sharp Score (mTSS) [Baseline (of Study 275-08-003), Week 0 (of this study) and Week 100]
X-ray images of extremities (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by at least two radiographic readers. The degree of joint destruction was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (complete collapse of bone). The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The mTSS ranges from 0 (normal) to 448 (worst).
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 74 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Subjects who participated in Study 275-08-003 and meet all of the criteria described below.
-
Patients who did not reach ACR20, and prematurely discontinued Study 275-08-003 at Week 16 or completed Study 275-08-003 by Week 24.
Exclusion Criteria:
-
Patients who experienced an important protocol deviation as mentioned below during Study 275-08-003.
-
Patients who received live or attenuated vaccines during Study 275-08-003 (Except for influenza or pneumococcal vaccines).
-
Patients who were found to have tuberculosis on a chest X-ray during Study 275-08-003.
-
Patients who required treatment for the same infection at two or more different times during Study 275-08-003
-
Women who are pregnant, are lactating, of childbearing potential and wish to conceive during the study and post-study 3 months.
-
Patients whom the investigator has decided to be inappropriate for participation in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chubu Region | Japan | |||
| 2 | Chugoku Region | Japan | |||
| 3 | Hokkaido Region | Japan | |||
| 4 | Kanto Region | Japan | |||
| 5 | Kinki Region | Japan | |||
| 6 | Kyushu Region | Japan | |||
| 7 | Shikoku Region | Japan | |||
| 8 | Tohoku Region | Japan |
Sponsors and Collaborators
- Astellas Pharma Inc
- UCB Japan Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00850343
Other Study ID Numbers:
- CDP870-275-08-004
- JapicCTI-090701
First Posted:
Feb 25, 2009
Last Update Posted:
Nov 2, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Astellas Pharma Inc
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Patients with rheumatoid arthritis (RA) who participated in Study 275-08-003 (NCT00791921) were eligible for this study. |
|---|---|
| Pre-assignment Detail | Participants were assigned to treatment groups based on whether they discontinued study 275-08-003 at Week 16 or completed Week 24 and based on American College of Rheumatology 20% (ACR20) response at Week 24. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Period Title: Overall Study | ||||
| STARTED | 110 | 12 | 43 | 43 |
| Completed Week 24 | 94 | 12 | 39 | 39 |
| Completed Week 52 | 88 | 11 | 37 | 37 |
| COMPLETED | 64 | 9 | 29 | 30 |
| NOT COMPLETED | 46 | 3 | 14 | 13 |
Baseline Characteristics
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Total of all reporting groups |
| Overall Participants | 110 | 12 | 43 | 43 | 208 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
55.4
(10.2)
|
59.3
(6.5)
|
54.6
(9.7)
|
55.9
(10.7)
|
55.5
(10.0)
|
| Age, Customized (participants) [Number] | |||||
| < 65 years |
90
81.8%
|
10
83.3%
|
35
81.4%
|
32
74.4%
|
167
80.3%
|
| ≧ 65 years |
20
18.2%
|
2
16.7%
|
8
18.6%
|
11
25.6%
|
41
19.7%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
91
82.7%
|
7
58.3%
|
28
65.1%
|
28
65.1%
|
154
74%
|
| Male |
19
17.3%
|
5
41.7%
|
15
34.9%
|
15
34.9%
|
54
26%
|
| Region of Enrollment (participants) [Number] | |||||
| Japan |
110
100%
|
12
100%
|
43
100%
|
43
100%
|
208
100%
|
| Body Weight (kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg] |
56.12
(10.84)
|
55.92
(9.55)
|
59.36
(11.11)
|
58.65
(11.83)
|
57.30
(11.06)
|
Outcome Measures
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | An adverse event (AE) is any untoward medical occurrence in a participant administered study drug which did not necessarily have a causal relationship with the treatment. In this study, events that occurred between the time of informed consent and the start of study medication were included in the adverse events for Study 275-08-003. Any event existing prior to the initiation of study treatment that was aggravated after initiation of study treatment was handled as a new event. The investigator assessed the severity of each AE as follows: Mild: No disruption of normal daily activities; Moderate: Affected normal daily activities; Severe: Inability to perform daily activities. A serious adverse event is an AE that results in death, is life-threatening, requires or prolongs inpatient hospitalization, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. |
| Time Frame | From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one study drug administration were included in the safety analysis population (SAF). |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 110 | 12 | 43 | 43 |
| Any adverse event |
102
92.7%
|
12
100%
|
41
95.3%
|
40
93%
|
| Mild adverse events |
16
14.5%
|
4
33.3%
|
7
16.3%
|
15
34.9%
|
| Moderate adverse events |
70
63.6%
|
6
50%
|
23
53.5%
|
18
41.9%
|
| Severe adverse events |
16
14.5%
|
2
16.7%
|
11
25.6%
|
7
16.3%
|
| Serious adverse events |
40
36.4%
|
3
25%
|
17
39.5%
|
16
37.2%
|
| Serious adverse events leading to death |
0
0%
|
1
8.3%
|
2
4.7%
|
0
0%
|
| Non-fatal serious adverse events |
40
36.4%
|
2
16.7%
|
16
37.2%
|
16
37.2%
|
| Adverse events leading to withdrawal |
16
14.5%
|
2
16.7%
|
6
14%
|
6
14%
|
| Infections induced by pathogen in study drug |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Overdoses |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Adverse events occurring within 2 hours of dosing |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With American College of Rheumatology 20% (ACR20) Response |
|---|---|
| Description | A participant was an ACR20 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 20% improvement in 68 tender joint count; ≥ 20% improvement in 66 swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). |
| Time Frame | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 110 | 12 | 43 | 43 |
| Week 24 |
60.9
55.4%
|
58.3
485.8%
|
90.7
210.9%
|
90.7
210.9%
|
| Week 52 |
70.0
63.6%
|
83.3
694.2%
|
76.7
178.4%
|
90.7
210.9%
|
| Final Assessment |
67.3
61.2%
|
75.0
625%
|
86.0
200%
|
88.4
205.6%
|
| Title | Percentage of Participants With American College of Rheumatology 50% (ACR50) Response |
|---|---|
| Description | A participant was an ACR50 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 50% improvement in 68 tender joint count; ≥ 50% improvement in 66 swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). |
| Time Frame | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 110 | 12 | 43 | 43 |
| Week 24 |
29.1
26.5%
|
41.7
347.5%
|
69.8
162.3%
|
74.4
173%
|
| Week 52 |
40.9
37.2%
|
58.3
485.8%
|
62.8
146%
|
69.8
162.3%
|
| Final Assessment |
47.3
43%
|
58.3
485.8%
|
67.4
156.7%
|
74.4
173%
|
| Title | Percentage of Participants With American College of Rheumatology 70% (ACR70) Response |
|---|---|
| Description | A participant was an ACR70 responder if the following 3 criteria for improvement from Baseline (before study drug administration in Study 275-08-003) were met: ≥ 70% improvement in 68 tender joint count; ≥ 70% improvement in 66 swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of arthritis pain (measured on a 100 mm visual analog scale [VAS]); Patient's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); C-Reactive Protein (CRP). |
| Time Frame | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 110 | 12 | 43 | 43 |
| Week 24 |
14.5
13.2%
|
16.7
139.2%
|
46.5
108.1%
|
48.8
113.5%
|
| Week 52 |
22.7
20.6%
|
16.7
139.2%
|
58.1
135.1%
|
46.5
108.1%
|
| Final Assessment |
29.1
26.5%
|
16.7
139.2%
|
60.5
140.7%
|
58.1
135.1%
|
| Title | Change From Baseline in Disease Activity Score (DAS) 28 |
|---|---|
| Description | The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count; 28 swollen joint count; Erythrocyte sedimentation rate (ESR); Patient's global assessment of disease activity. To obtain the tender joint count and swollen joint count, 28 joints of the shoulder, elbow, wrist, metacarpophalangeal joints, thumb interphalangeal joints, proximal interphalangeal joints, and knee joints were examined. The data before study drug administration of 275-08-003 Study was utilized for Baseline. DAS28(ESR) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible ESR. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 or less indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission. |
| Time Frame | Baseline (of Study 275-08-003), Week 24, Week 52 and at the final assessment (maximum was 208 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) included all randomized participants who received at least one dose of study drug with at least one post-baseline efficacy data point. Last observation carried forward (LOCF) was used. "N" indicates the number of participants with available data at each time point. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 110 | 12 | 43 | 43 |
| Week 24 [N=110, 12, 43, 43] |
-1.87
(1.31)
|
-2.46
(1.18)
|
-3.10
(1.28)
|
-2.87
(1.40)
|
| Week 52 [N=109, 12, 43, 43] |
-2.15
(1.37)
|
-2.53
(0.90)
|
-2.93
(1.47)
|
-2.98
(1.11)
|
| Final Assessment [N=110, 12, 43, 43] |
-2.23
(1.63)
|
-2.31
(1.21)
|
-2.98
(1.58)
|
-2.93
(1.24)
|
| Title | Change From Baseline in Modified Total Sharp Score (mTSS) |
|---|---|
| Description | X-ray images of extremities (posteroanterior views of both hands and dorsoplantar views of both feet) were independently assessed by at least two radiographic readers. The degree of joint destruction was graded by assessing bone erosion in 44 joints and joint space narrowing (JSN) in 42 joints. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (complete collapse of bone). The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The mTSS ranges from 0 (normal) to 448 (worst). |
| Time Frame | Baseline (of Study 275-08-003), Week 0 (of this study) and Week 100 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set with available mTSS data. Linear extrapolation method was used. |
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. |
| Measure Participants | 87 | 11 | 37 | 37 |
| Change from Baseline to Week 0 |
1.48
(2.67)
|
2.18
(2.91)
|
0.77
(3.00)
|
-0.05
(1.22)
|
| Change from Baseline to Week 100 [N=82, 11, 35, 36 |
7.89
(14.23)
|
8.73
(11.54)
|
2.07
(6.72)
|
1.85
(4.24)
|
Adverse Events
| Time Frame | From the first dosing of this study up to 12 weeks (84 days) after the last dosing. The dosing was allowed until launch of certolizumab pegol for RA in Japan. The maximum duration on study drug was 204 weeks. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least one study drug administration were included in the safety analysis population (SAF). | |||||||
| Arm/Group Title | Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | ||||
| Arm/Group Description | Participants who were ACR20 non-responders and discontinued study 275-08-003 at Week 16 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 non-responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 200 mg certolizumab pegol by subcutaneous injection once every 2 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | Participants who were ACR20 responders and completed study 275-08-003 at Week 24 received 400 mg certolizumab pegol by subcutaneous injection once every 4 weeks for up to 52 weeks or until approval of certolizumab pegol for rheumatoid arthritis in Japan. | ||||
All Cause Mortality |
||||||||
| Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 40/110 (36.4%) | 3/12 (25%) | 17/43 (39.5%) | 16/43 (37.2%) | ||||
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Angina pectoris | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Myocardial infraction | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Pericarditis | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Cardiac disorder | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness neurosensory | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Sudden hearing loss | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Colitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Colonic polyp | 2/110 (1.8%) | 1/12 (8.3%) | 3/43 (7%) | 0/43 (0%) | ||||
| Duodenal ulcer | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Peritonitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Upper gastrointestinal haemorrhage | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Haemorrhoidal haemorrhage | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| General disorders | ||||||||
| Chest discomfort | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Pyrexia | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Liver disorder | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Infections and infestations | ||||||||
| Acute sinusitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Aspergillosis | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Bronchopneumonia | 2/110 (1.8%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Cystitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Gastroenteritis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Herpes zoster | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Pneumonia | 1/110 (0.9%) | 1/12 (8.3%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Postoperative wound infection | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Pyothorax | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Septic shock | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Wound infection | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Arthritis bacterial | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Staphylococcal sepsis | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Psoas abscess | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Pneumonia bacterial | 2/110 (1.8%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Herpes zoster oticus | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Foot fracture | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Radius fracture | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Spinal compression fracture | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Tendon rupture | 2/110 (1.8%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Tibia fracture | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Meniscus lesion | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Procedural pain | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Investigations | ||||||||
| Computerised tomogram thorax abnormal | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Ankylosing spondylitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Arthralgia | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Arthropathy | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Joint destruction | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Lumbar spinal stenosis | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Osteonecrosis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Rheumatoid arthritis | 4/110 (3.6%) | 0/12 (0%) | 0/43 (0%) | 2/43 (4.7%) | ||||
| Scoliosis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Synovitis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Intervertebral disc protrusion | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Wrist deformity | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Adenoma benign | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Breast cancer | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Gastric cancer | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Lymphoma | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Malignant pleural effusion | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Non-Hodgkin's lymphoma | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Colon adenoma | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Hepatic cancer metastatic | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Lung neoplasm malignant | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Ovarian neoplasm | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Nervous system disorders | ||||||||
| Brain stem haemorrhage | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Cerebral infarction | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Dizziness postural | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Migraine | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Multiple sclerosis | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Sciatica | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Subarachnoid haemorrhage | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Thoracic outlet syndrome | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Pregnancy, puerperium and perinatal conditions | ||||||||
| Abortion spontaneous | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Psychiatric disorders | ||||||||
| Completed suicide | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Depression | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Anxiety disorder | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Calculus ureteric | 2/110 (1.8%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Interstitial lung disease | 2/110 (1.8%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Pleural effusion | 0/110 (0%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermal cyst | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Social circumstances | ||||||||
| Overwork | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Joint arthroplasty | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Vascular disorders | ||||||||
| Aortic aneurysm | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Aortic dissection | 0/110 (0%) | 0/12 (0%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Hypertension | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
| Lymphoedema | 1/110 (0.9%) | 0/12 (0%) | 0/43 (0%) | 0/43 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Discontinued Non-responders 200 mg | Completed Non-responders 200 mg | Completed Responders 200 mg | Completed Responders 400 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 102/110 (92.7%) | 12/12 (100%) | 41/43 (95.3%) | 40/43 (93%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Iron deficiency anaemia | 4/110 (3.6%) | 1/12 (8.3%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 3/110 (2.7%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Vertigo positional | 2/110 (1.8%) | 1/12 (8.3%) | 2/43 (4.7%) | 0/43 (0%) | ||||
| Eye disorders | ||||||||
| Blepharitis | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 4/43 (9.3%) | ||||
| Cataract | 2/110 (1.8%) | 0/12 (0%) | 3/43 (7%) | 1/43 (2.3%) | ||||
| Conjunctivitis | 5/110 (4.5%) | 1/12 (8.3%) | 3/43 (7%) | 4/43 (9.3%) | ||||
| Conjunctivitis allergic | 8/110 (7.3%) | 0/12 (0%) | 4/43 (9.3%) | 3/43 (7%) | ||||
| Diplopia | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Keratitis | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/110 (0%) | 0/12 (0%) | 3/43 (7%) | 0/43 (0%) | ||||
| Abdominal pain upper | 3/110 (2.7%) | 0/12 (0%) | 3/43 (7%) | 0/43 (0%) | ||||
| Colonic polyp | 2/110 (1.8%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Constipation | 14/110 (12.7%) | 2/12 (16.7%) | 3/43 (7%) | 3/43 (7%) | ||||
| Dental caries | 7/110 (6.4%) | 0/12 (0%) | 2/43 (4.7%) | 1/43 (2.3%) | ||||
| Diarrhoea | 9/110 (8.2%) | 2/12 (16.7%) | 3/43 (7%) | 3/43 (7%) | ||||
| Dyspepsia | 1/110 (0.9%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Enterocolitis | 1/110 (0.9%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Gastritis | 7/110 (6.4%) | 1/12 (8.3%) | 4/43 (9.3%) | 1/43 (2.3%) | ||||
| Gastritis atrophic | 0/110 (0%) | 1/12 (8.3%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Nausea | 3/110 (2.7%) | 0/12 (0%) | 4/43 (9.3%) | 1/43 (2.3%) | ||||
| Periodontitis | 11/110 (10%) | 0/12 (0%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Reflux oesophagitis | 1/110 (0.9%) | 0/12 (0%) | 3/43 (7%) | 0/43 (0%) | ||||
| Stomach discomfort | 6/110 (5.5%) | 0/12 (0%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Stomatitis | 6/110 (5.5%) | 0/12 (0%) | 5/43 (11.6%) | 3/43 (7%) | ||||
| General disorders | ||||||||
| Injection site reaction | 4/110 (3.6%) | 2/12 (16.7%) | 2/43 (4.7%) | 0/43 (0%) | ||||
| Mass | 0/110 (0%) | 1/12 (8.3%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 9/110 (8.2%) | 2/12 (16.7%) | 1/43 (2.3%) | 2/43 (4.7%) | ||||
| Hepatic steatosis | 3/110 (2.7%) | 0/12 (0%) | 5/43 (11.6%) | 0/43 (0%) | ||||
| Liver disorder | 2/110 (1.8%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Gallbladder polyp | 0/110 (0%) | 1/12 (8.3%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Immune system disorders | ||||||||
| Seasonal allergy | 13/110 (11.8%) | 0/12 (0%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 12/110 (10.9%) | 2/12 (16.7%) | 8/43 (18.6%) | 6/43 (14%) | ||||
| Cellulitis | 3/110 (2.7%) | 1/12 (8.3%) | 0/43 (0%) | 2/43 (4.7%) | ||||
| Cystitis | 9/110 (8.2%) | 0/12 (0%) | 2/43 (4.7%) | 2/43 (4.7%) | ||||
| Gastroenteritis | 8/110 (7.3%) | 1/12 (8.3%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Herpes zoster | 8/110 (7.3%) | 0/12 (0%) | 3/43 (7%) | 4/43 (9.3%) | ||||
| Influenza | 7/110 (6.4%) | 1/12 (8.3%) | 2/43 (4.7%) | 3/43 (7%) | ||||
| Nasopharyngitis | 42/110 (38.2%) | 2/12 (16.7%) | 18/43 (41.9%) | 19/43 (44.2%) | ||||
| Oesophageal candidiasis | 1/110 (0.9%) | 2/12 (16.7%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Paronychia | 2/110 (1.8%) | 1/12 (8.3%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Pharyngitis | 17/110 (15.5%) | 0/12 (0%) | 7/43 (16.3%) | 7/43 (16.3%) | ||||
| Pneumonia | 5/110 (4.5%) | 2/12 (16.7%) | 4/43 (9.3%) | 2/43 (4.7%) | ||||
| Sinusitis | 7/110 (6.4%) | 0/12 (0%) | 3/43 (7%) | 1/43 (2.3%) | ||||
| Tinea pedis | 8/110 (7.3%) | 0/12 (0%) | 4/43 (9.3%) | 2/43 (4.7%) | ||||
| Upper respiratory tract infection | 14/110 (12.7%) | 2/12 (16.7%) | 9/43 (20.9%) | 4/43 (9.3%) | ||||
| Tinea infection | 2/110 (1.8%) | 1/12 (8.3%) | 2/43 (4.7%) | 0/43 (0%) | ||||
| Oral herpes | 7/110 (6.4%) | 0/12 (0%) | 2/43 (4.7%) | 1/43 (2.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arthropod sting | 4/110 (3.6%) | 0/12 (0%) | 4/43 (9.3%) | 0/43 (0%) | ||||
| Dislocation of vertebra | 2/110 (1.8%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Spinal compression fracture | 6/110 (5.5%) | 0/12 (0%) | 1/43 (2.3%) | 0/43 (0%) | ||||
| Vaccination complication | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Contusion | 12/110 (10.9%) | 0/12 (0%) | 6/43 (14%) | 2/43 (4.7%) | ||||
| Investigations | ||||||||
| Blood creatinine increased | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Chest X-ray abnormal | 1/110 (0.9%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 5/110 (4.5%) | 0/12 (0%) | 4/43 (9.3%) | 3/43 (7%) | ||||
| Rheumatoid arthritis | 15/110 (13.6%) | 3/12 (25%) | 6/43 (14%) | 6/43 (14%) | ||||
| Spinal osteoarthritis | 3/110 (2.7%) | 0/12 (0%) | 2/43 (4.7%) | 3/43 (7%) | ||||
| Tenosynovitis | 1/110 (0.9%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Rheumatoid nodule | 1/110 (0.9%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Lower extremity mass | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Intervertebral disc protrusion | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 3/43 (7%) | ||||
| Musculoskeletal stiffness | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Conjunctival neoplasm | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Nervous system disorders | ||||||||
| Headache | 6/110 (5.5%) | 0/12 (0%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 7/110 (6.4%) | 1/12 (8.3%) | 7/43 (16.3%) | 3/43 (7%) | ||||
| Sleep disorder | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 1/43 (2.3%) | ||||
| Renal and urinary disorders | ||||||||
| Calculus urinary | 0/110 (0%) | 1/12 (8.3%) | 1/43 (2.3%) | 1/43 (2.3%) | ||||
| Hypertonic bladder | 1/110 (0.9%) | 0/12 (0%) | 1/43 (2.3%) | 3/43 (7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 2/110 (1.8%) | 0/12 (0%) | 1/43 (2.3%) | 3/43 (7%) | ||||
| Pleurisy | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Rhinitis allergic | 3/110 (2.7%) | 2/12 (16.7%) | 4/43 (9.3%) | 2/43 (4.7%) | ||||
| Upper respiratory tract inflammation | 5/110 (4.5%) | 1/12 (8.3%) | 1/43 (2.3%) | 5/43 (11.6%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermal cyst | 3/110 (2.7%) | 1/12 (8.3%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Dermatitis contact | 7/110 (6.4%) | 0/12 (0%) | 6/43 (14%) | 6/43 (14%) | ||||
| Drug eruption | 0/110 (0%) | 0/12 (0%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Eczema | 20/110 (18.2%) | 2/12 (16.7%) | 12/43 (27.9%) | 5/43 (11.6%) | ||||
| Eczema asteatotic | 3/110 (2.7%) | 0/12 (0%) | 5/43 (11.6%) | 2/43 (4.7%) | ||||
| Haemorrhage subcutaneous | 0/110 (0%) | 1/12 (8.3%) | 1/43 (2.3%) | 2/43 (4.7%) | ||||
| Hyperkeratosis | 4/110 (3.6%) | 0/12 (0%) | 0/43 (0%) | 4/43 (9.3%) | ||||
| Pruritus | 8/110 (7.3%) | 0/12 (0%) | 1/43 (2.3%) | 5/43 (11.6%) | ||||
| Rash | 12/110 (10.9%) | 0/12 (0%) | 1/43 (2.3%) | 2/43 (4.7%) | ||||
| Seborrhoeic dermatitis | 2/110 (1.8%) | 0/12 (0%) | 3/43 (7%) | 2/43 (4.7%) | ||||
| Urticaria | 5/110 (4.5%) | 1/12 (8.3%) | 2/43 (4.7%) | 1/43 (2.3%) | ||||
| Vascular disorders | ||||||||
| Aortic aneurysm | 0/110 (0%) | 1/12 (8.3%) | 0/43 (0%) | 0/43 (0%) | ||||
| Hypertension | 11/110 (10%) | 1/12 (8.3%) | 2/43 (4.7%) | 3/43 (7%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication to seek patent protection.
Results Point of Contact
| Name/Title | Medical Director, Global Medical Sciences |
|---|---|
| Organization | Astellas Pharma Inc. |
| Phone | |
| ClinicalTrials.Disclosure@astellas.com |
Responsible Party:
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT00850343
Other Study ID Numbers:
- CDP870-275-08-004
- JapicCTI-090701
First Posted:
Feb 25, 2009
Last Update Posted:
Nov 2, 2014
Last Verified:
Oct 1, 2014