Efficacy and Safety of Increased Dose of TA-650(Infliximab) in Patients With Rheumatoid Arthritis
Sponsor
Mitsubishi Tanabe Pharma Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT00691028
Collaborator
(none)
327
3
19.9
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the efficacy, safety and pharmacokinetics of maintenance treatment with 3mg/kg, 6mg/kg or 10mg/kg of TA-650 in combination with methotrexate (MTX) after three infusions (weeks-0, 2, 6) of 3mg/kg in Rheumatoid Arthritis (RA) showing an insufficient response to MTX.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
327 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Clinical Study to Assess the Efficacy and Safety of Increased Dose of TA-650(Infliximab) in Patients With Rheumatoid Arthritis
Study Start Date
:
Sep 1, 2005
Actual Primary Completion Date
:
May 1, 2007
Actual Study Completion Date
:
May 1, 2007
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TA-650 3 mg/kg
|
Drug: TA-650 3 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6. Then 3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.
Other Names:
|
| Experimental: TA-650 6 mg/kg
|
Drug: TA-650 6 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6 weeks. Then 6 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.
Other Names:
|
| Experimental: TA-650 10 mg/kg
|
Drug: TA-650 10 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6. Then 10 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Numeric Index of American College of Rheumatology Response (ACR-N, N Shows the Percent Improvement) [baseline and week 54]
The ACR-N index of improvement is the minimum of the following: (1) the percent decrease from baseline in tender joint counts(TJC) or (2) the percent decrease from baseline in swollen joint counts(SJC) or (3) the median percent decrease from baseline for the following: a. Patient's assessment of pain (visual analog scale (VAS) 0-100, 100 worst pain); b. Patient's global assessment of disease activity (VAS 0-100); c. Physician's global assessment of disease activity (VAS 0-100); d. Physical function as measured by the Health Assessment Questionnaire(HAQ)(0-3); e. C-Reactive Protein(CRP) measurement. Higher numbers (maximum:100) indicate more improvement.
Secondary Outcome Measures
- Percentage of Participants Achieving American College of Rheumatology 20, 50 and 70% Response (ACR20, 50, 70) [54 weeks]
ACR 20 (50 or 70) response is a decrease of at least 20% (50% or 70%) in both TJC and SJC and in 3 to 5 assessments (patient's assessment of pain [VAS] with 0, no pain to 100, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 100, very poor and 0, no arthritis activity to 100, extremely active, respectively]; [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; [CRP])
- Tender Joint Counts (TJC) [54 weeks]
The TJC was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The TJC was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.
- Swollen Joint Count (SJC) [54 weeks]
The SJC was determined by examination of 66 joints and identifying when swelling was present. The SJC was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.
- CRP Level [54 weeks]
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Normal range of CRP is 0 mg/dL to 0.3 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
- Change From Baseline in DAS28 [baseline and week 54]
DAS28 is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Total score range:0 to 9.4, higher score indicated more disease activity. DAS28 =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 to 9.4 implied high disease activity and <2.6 implied remission.
- Change From Baseline to Week 54 in HAQ [54 weeks]
HAQ: patient's assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.
- Change in Modified Total Sharp Score (mTSS) at week54 From Baseline [baseline and week 54]
The mTSS is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 54 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 and joint space narrowing on a scale of 0 (no damage) to 4. Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 390 [maximal disease]). An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
- Pharmacokinetics- Serum Concentration of Infliximab [54 weeks]
Serum level of infliximab was measured by enzyme-linked immunosorbent assay (ELISA), using a monoclonal antibody against infliximab. The lowest level of infliximab that could be reliably detected was 0.1 ug/ml.
- Pharmacokinetics Positive- ATI [54 weeks]
ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Patients with active RA in spite of stable dose of MTX
Exclusion Criteria:
-
Having received infliximab in the past
-
Having a history of serious infection which caused hospitalization within 6 months before the registration
-
Having an active tuberculosis
-
Having a complication or a history of malignancy within 5 years before the registration
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Mitsubishi Tanabe Pharma Corporation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00691028
Other Study ID Numbers:
- TA-650-13
- JapicCTI-050146
First Posted:
Jun 5, 2008
Last Update Posted:
Mar 4, 2014
Last Verified:
Jan 1, 2014
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg | Open-label |
|---|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. | 327 patients received TA-650 at 3 mg/kg treatment during the open-label period. |
| Period Title: Open-label Period | ||||
| STARTED | 0 | 0 | 0 | 327 |
| COMPLETED | 0 | 0 | 0 | 307 |
| NOT COMPLETED | 0 | 0 | 0 | 20 |
| Period Title: Open-label Period | ||||
| STARTED | 99 | 104 | 104 | 0 |
| COMPLETED | 86 | 91 | 95 | 0 |
| NOT COMPLETED | 13 | 13 | 9 | 0 |
Baseline Characteristics
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. | Total of all reporting groups |
| Overall Participants | 99 | 104 | 104 | 307 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
89
89.9%
|
96
92.3%
|
92
88.5%
|
277
90.2%
|
| >=65 years |
10
10.1%
|
8
7.7%
|
12
11.5%
|
30
9.8%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
49.7
(11.7)
|
48.8
(11.8)
|
50.4
(12.5)
|
49.6
(12.0)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
78
78.8%
|
86
82.7%
|
89
85.6%
|
253
82.4%
|
| Male |
21
21.2%
|
18
17.3%
|
15
14.4%
|
54
17.6%
|
Outcome Measures
| Title | Numeric Index of American College of Rheumatology Response (ACR-N, N Shows the Percent Improvement) |
|---|---|
| Description | The ACR-N index of improvement is the minimum of the following: (1) the percent decrease from baseline in tender joint counts(TJC) or (2) the percent decrease from baseline in swollen joint counts(SJC) or (3) the median percent decrease from baseline for the following: a. Patient's assessment of pain (visual analog scale (VAS) 0-100, 100 worst pain); b. Patient's global assessment of disease activity (VAS 0-100); c. Physician's global assessment of disease activity (VAS 0-100); d. Physical function as measured by the Health Assessment Questionnaire(HAQ)(0-3); e. C-Reactive Protein(CRP) measurement. Higher numbers (maximum:100) indicate more improvement. |
| Time Frame | baseline and week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Mean (Standard Deviation) [percent change] |
51.3
(32.1)
|
53.8
(34.4)
|
58.3
(31.3)
|
| Title | Percentage of Participants Achieving American College of Rheumatology 20, 50 and 70% Response (ACR20, 50, 70) |
|---|---|
| Description | ACR 20 (50 or 70) response is a decrease of at least 20% (50% or 70%) in both TJC and SJC and in 3 to 5 assessments (patient's assessment of pain [VAS] with 0, no pain to 100, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 100, very poor and 0, no arthritis activity to 100, extremely active, respectively]; [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; [CRP]) |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| ACR20% improvement(percentage) |
75.8
76.6%
|
78.8
75.8%
|
82.7
79.5%
|
| ACR50% improvement (percentage) |
60.6
61.2%
|
58.7
56.4%
|
66.3
63.8%
|
| ACR70% improvement (percentage) |
37.4
37.8%
|
42.3
40.7%
|
43.3
41.6%
|
| Title | Tender Joint Counts (TJC) |
|---|---|
| Description | The TJC was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The TJC was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Tender joint count, baseline |
18.6
(11.3)
|
18.0
(10.5)
|
17.5
(10.9)
|
| Tender joint count, week54 |
6.3
(8.6)
|
4.8
(7.7)
|
4.8
(7.6)
|
| Title | Swollen Joint Count (SJC) |
|---|---|
| Description | The SJC was determined by examination of 66 joints and identifying when swelling was present. The SJC was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14.. |
| Measure Participants | 99 | 104 | 104 |
| Swollen joint count, baseline |
14.2
(6.1)
|
13.1
(8.4)
|
13.7
(7.3)
|
| Swollen joint count, week 54 |
3.6
(4.8)
|
3.3
(4.6)
|
3.0
(4.6)
|
| Title | CRP Level |
|---|---|
| Description | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Normal range of CRP is 0 mg/dL to 0.3 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14.. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| CRP level, baseline |
2.5
|
2.3
|
2.3
|
| CRP level, week 54 |
0.5
|
0.4
|
0.2
|
| Title | Change From Baseline in DAS28 |
|---|---|
| Description | DAS28 is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Total score range:0 to 9.4, higher score indicated more disease activity. DAS28 =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 to 9.4 implied high disease activity and <2.6 implied remission. |
| Time Frame | baseline and week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14.. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Mean (Standard Deviation) [units on a scale] |
-2.30
(1.56)
|
-2.57
(1.69)
|
-2.80
(1.58)
|
| Title | Change From Baseline to Week 54 in HAQ |
|---|---|
| Description | HAQ: patient's assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Mean (Standard Deviation) [units on a scale] |
-0.48
(0.70)
|
-0.56
(0.64)
|
-0.59
(0.63)
|
| Title | Change in Modified Total Sharp Score (mTSS) at week54 From Baseline |
|---|---|
| Description | The mTSS is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 54 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 and joint space narrowing on a scale of 0 (no damage) to 4. Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 390 [maximal disease]). An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. |
| Time Frame | baseline and week 54 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Median (Inter-Quartile Range) [score] |
0.00
|
0.48
|
0.00
|
| Title | Pharmacokinetics- Serum Concentration of Infliximab |
|---|---|
| Description | Serum level of infliximab was measured by enzyme-linked immunosorbent assay (ELISA), using a monoclonal antibody against infliximab. The lowest level of infliximab that could be reliably detected was 0.1 ug/ml. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Pharmacokinetics Positive- ATI |
|---|---|
| Description | ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay. |
| Time Frame | 54 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TA-650 3 mg/kg | TA-650 6 mg/kg | TA-650 10 mg/kg |
|---|---|---|---|
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| Measure Participants | 99 | 104 | 104 |
| Number [participants] |
27
27.3%
|
24
23.1%
|
13
12.5%
|
Adverse Events
| Time Frame | 54 weeks | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | TA-650 3 mg/kg (Double-blind) | TA-650 6 mg/kg (Double-blind) | TA-650 10 mg/kg (Double-blind) | Open-label | ||||
| Arm/Group Description | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. | 327 patients received TA-650 at 3 mg/kg treatment during the open-label period. | ||||
All Cause Mortality |
||||||||
| TA-650 3 mg/kg (Double-blind) | TA-650 6 mg/kg (Double-blind) | TA-650 10 mg/kg (Double-blind) | Open-label | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| TA-650 3 mg/kg (Double-blind) | TA-650 6 mg/kg (Double-blind) | TA-650 10 mg/kg (Double-blind) | Open-label | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/99 (7.1%) | 5/104 (4.8%) | 9/104 (8.7%) | 17/327 (5.2%) | ||||
| Cardiac disorders | ||||||||
| Pericardial effusion | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Pericarditis | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Retinal vein occlusion | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Ascites | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Enterocolitis | 1/99 (1%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Gastric ulcer perforation | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Inguinal hernia | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Mallory-Weiss syndrome | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Pancreatitis acute | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Peritonitis | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Gastrointestinal haemorrhage | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| General disorders | ||||||||
| Gait disturbance | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Hepatobiliary disorders | ||||||||
| Bile duct obstruction | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Immune system disorders | ||||||||
| Anaphylactoid reaction | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Infections and infestations | ||||||||
| Cryptococcosis | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Gastroenteritis | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 2/327 (0.6%) | ||||
| Osteomyelitis | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Pneumonia legionella | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Pyelonephritis | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Sepsis | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Tonsillitis | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Pneumonia bacterial | 0/99 (0%) | 0/104 (0%) | 2/104 (1.9%) | 2/327 (0.6%) | ||||
| Bronchiolitis | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Pneumocystis jiroveci pneumonia | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Anastomotic ulcer | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Ulna fracture | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Hand fracture | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Joint dislocation | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Osteonecrosis | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Rheumatoid arthritis | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Bile duct cancer | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Breast cancer | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Tongue neoplasm malignant stage unspecified | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Uterine cancer | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Thyroid cancer | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Nervous system disorders | ||||||||
| Carpal tunnel syndrome | 0/99 (0%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Loss of consciousness | 0/99 (0%) | 0/104 (0%) | 0/104 (0%) | 1/327 (0.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Interstitial lung disease | 0/99 (0%) | 0/104 (0%) | 1/104 (1%) | 1/327 (0.3%) | ||||
| Pleural effusion | 1/99 (1%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| TA-650 3 mg/kg (Double-blind) | TA-650 6 mg/kg (Double-blind) | TA-650 10 mg/kg (Double-blind) | Open-label | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 93/99 (93.9%) | 93/104 (89.4%) | 96/104 (92.3%) | 153/327 (46.8%) | ||||
| Cardiac disorders | ||||||||
| Palpitations | 0/99 (0%) | 5/104 (4.8%) | 0/104 (0%) | 7/327 (2.1%) | ||||
| Ear and labyrinth disorders | ||||||||
| Vertigo | 2/99 (2%) | 1/104 (1%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Eye disorders | ||||||||
| Conjunctivitis | 3/99 (3%) | 1/104 (1%) | 2/104 (1.9%) | 0/327 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 2/99 (2%) | 5/104 (4.8%) | 0/104 (0%) | 0/327 (0%) | ||||
| Constipation | 2/99 (2%) | 3/104 (2.9%) | 1/104 (1%) | 0/327 (0%) | ||||
| Dental caries | 2/99 (2%) | 2/104 (1.9%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Diarrhoea | 2/99 (2%) | 1/104 (1%) | 4/104 (3.8%) | 7/327 (2.1%) | ||||
| Dyspepsia | 0/99 (0%) | 0/104 (0%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Nausea | 0/99 (0%) | 4/104 (3.8%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Stomach discomfort | 1/99 (1%) | 1/104 (1%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Stomatitis | 5/99 (5.1%) | 2/104 (1.9%) | 5/104 (4.8%) | 0/327 (0%) | ||||
| General disorders | ||||||||
| Chest discomfort | 0/99 (0%) | 1/104 (1%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Chest pain | 0/99 (0%) | 3/104 (2.9%) | 2/104 (1.9%) | 0/327 (0%) | ||||
| Malaise | 0/99 (0%) | 2/104 (1.9%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Pyrexia | 6/99 (6.1%) | 6/104 (5.8%) | 4/104 (3.8%) | 12/327 (3.7%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 8/99 (8.1%) | 3/104 (2.9%) | 3/104 (2.9%) | 11/327 (3.4%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 2/99 (2%) | 5/104 (4.8%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Gastroenteritis | 3/99 (3%) | 2/104 (1.9%) | 1/104 (1%) | 0/327 (0%) | ||||
| Herpes zoster | 0/99 (0%) | 2/104 (1.9%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Nasopharyngitis | 29/99 (29.3%) | 29/104 (27.9%) | 30/104 (28.8%) | 56/327 (17.1%) | ||||
| Oral candidiasis | 2/99 (2%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Paronychia | 4/99 (4%) | 1/104 (1%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Pharyngitis | 4/99 (4%) | 0/104 (0%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Pneumonia | 4/99 (4%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Sinusitis | 4/99 (4%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Tinea infection | 1/99 (1%) | 3/104 (2.9%) | 1/104 (1%) | 0/327 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 3/99 (3%) | 0/104 (0%) | 4/104 (3.8%) | 0/327 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/99 (1%) | 12/104 (11.5%) | 14/104 (13.5%) | 33/327 (10.1%) | ||||
| Aspartate aminotransferase increased | 1/99 (1%) | 8/104 (7.7%) | 8/104 (7.7%) | 20/327 (6.1%) | ||||
| Blood pressure increased | 1/99 (1%) | 3/104 (2.9%) | 4/104 (3.8%) | 11/327 (3.4%) | ||||
| Gamma-glutamyltransferase increased | 2/99 (2%) | 3/104 (2.9%) | 1/104 (1%) | 0/327 (0%) | ||||
| Blood urine present | 3/99 (3%) | 4/104 (3.8%) | 5/104 (4.8%) | 0/327 (0%) | ||||
| Heart rate increased | 0/99 (0%) | 3/104 (2.9%) | 0/104 (0%) | 0/327 (0%) | ||||
| Liver function test abnormal | 4/99 (4%) | 3/104 (2.9%) | 0/104 (0%) | 7/327 (2.1%) | ||||
| White blood cell count decreased | 1/99 (1%) | 2/104 (1.9%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| White blood cell count increased | 3/99 (3%) | 2/104 (1.9%) | 2/104 (1.9%) | 0/327 (0%) | ||||
| Protein urine present | 1/99 (1%) | 3/104 (2.9%) | 0/104 (0%) | 0/327 (0%) | ||||
| Blood alkaline phosphatase increased | 0/99 (0%) | 4/104 (3.8%) | 0/104 (0%) | 0/327 (0%) | ||||
| Antinuclear antibody positive | 25/99 (25.3%) | 15/104 (14.4%) | 17/104 (16.3%) | 0/327 (0%) | ||||
| DNA antibody positive | 65/99 (65.7%) | 58/104 (55.8%) | 54/104 (51.9%) | 16/327 (4.9%) | ||||
| Cell marker increased | 2/99 (2%) | 2/104 (1.9%) | 1/104 (1%) | 0/327 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 2/99 (2%) | 4/104 (3.8%) | 0/104 (0%) | 0/327 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 2/99 (2%) | 4/104 (3.8%) | 4/104 (3.8%) | 7/327 (2.1%) | ||||
| Headache | 8/99 (8.1%) | 4/104 (3.8%) | 4/104 (3.8%) | 7/327 (2.1%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Choking sensation | 2/99 (2%) | 1/104 (1%) | 0/104 (0%) | 0/327 (0%) | ||||
| Cough | 3/99 (3%) | 1/104 (1%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Pharyngolaryngeal pain | 4/99 (4%) | 3/104 (2.9%) | 3/104 (2.9%) | 0/327 (0%) | ||||
| Productive cough | 2/99 (2%) | 0/104 (0%) | 1/104 (1%) | 0/327 (0%) | ||||
| Upper respiratory tract inflammation | 6/99 (6.1%) | 9/104 (8.7%) | 9/104 (8.7%) | 13/327 (4%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/99 (0%) | 3/104 (2.9%) | 2/104 (1.9%) | 0/327 (0%) | ||||
| Dermatitis contact | 4/99 (4%) | 0/104 (0%) | 2/104 (1.9%) | 0/327 (0%) | ||||
| Eczema | 4/99 (4%) | 3/104 (2.9%) | 0/104 (0%) | 0/327 (0%) | ||||
| Heat rash | 3/99 (3%) | 0/104 (0%) | 0/104 (0%) | 0/327 (0%) | ||||
| Pruritus | 4/99 (4%) | 4/104 (3.8%) | 5/104 (4.8%) | 0/327 (0%) | ||||
| Rash | 12/99 (12.1%) | 12/104 (11.5%) | 9/104 (8.7%) | 18/327 (5.5%) | ||||
| Urticaria | 4/99 (4%) | 5/104 (4.8%) | 3/104 (2.9%) | 0/327 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Clinical Trials, Information Desk |
|---|---|
| Organization | Mitsubishi Tanabe Pharma Corporation |
| Phone | |
| cti-inq-ml@ml.mt-pharma.co.jp |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00691028
Other Study ID Numbers:
- TA-650-13
- JapicCTI-050146
First Posted:
Jun 5, 2008
Last Update Posted:
Mar 4, 2014
Last Verified:
Jan 1, 2014