Trial Outcomes & Findings for A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis (NCT NCT00048932)
NCT ID: NCT00048932
Last Updated: 2011-11-24
Results Overview
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related SAE/AE = possibly, probably, or certainly related to study drug
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1795 participants
Primary outcome timeframe
Day 365 to Day 1,821
Results posted on
2011-11-24
Participant Flow
1795 enrolled in study and 339 were not randomized due to no longer meeting study criteria (n=214), withdraw of consent (n=83), other reasons (n=32), participant was lost to follow-up (n=5), administrative reason by sponsor (n=2), adverse event (n=2), and poor/non-compliance (n=1). Of 1456 randomized, 15 were not treated.
Participant milestones
| Measure |
Abatacept (ABA)
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Open Label (OL) Abatacept
Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
|
|---|---|---|---|
|
Double Blind Period (DB)
STARTED
|
959
|
482
|
0
|
|
Double Blind Period (DB)
COMPLETED
|
836
|
395
|
0
|
|
Double Blind Period (DB)
NOT COMPLETED
|
123
|
87
|
0
|
|
Open Label Period (OL)
STARTED
|
0
|
0
|
1184
|
|
Open Label Period (OL)
COMPLETED
|
0
|
0
|
743
|
|
Open Label Period (OL)
NOT COMPLETED
|
0
|
0
|
441
|
Reasons for withdrawal
| Measure |
Abatacept (ABA)
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Open Label (OL) Abatacept
Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
|
|---|---|---|---|
|
Double Blind Period (DB)
Administrative Reason By Sponsor
|
1
|
0
|
0
|
|
Double Blind Period (DB)
Adverse Event
|
51
|
19
|
0
|
|
Double Blind Period (DB)
Death
|
5
|
3
|
0
|
|
Double Blind Period (DB)
Lack of Efficacy
|
26
|
44
|
0
|
|
Double Blind Period (DB)
Lost to Follow-up
|
3
|
4
|
0
|
|
Double Blind Period (DB)
Relocation
|
1
|
0
|
0
|
|
Double Blind Period (DB)
Uncontrolled hypertension
|
0
|
1
|
0
|
|
Double Blind Period (DB)
Missed 2 doses while undergoing work-up
|
1
|
0
|
0
|
|
Double Blind Period (DB)
Pregnancy
|
1
|
0
|
0
|
|
Double Blind Period (DB)
No Longer Meets Study Criteria
|
8
|
2
|
0
|
|
Double Blind Period (DB)
Withdrawal by Subject
|
24
|
10
|
0
|
|
Double Blind Period (DB)
Poor/Non-Compliance
|
2
|
4
|
0
|
|
Open Label Period (OL)
Death
|
0
|
0
|
25
|
|
Open Label Period (OL)
Adverse Event
|
0
|
0
|
103
|
|
Open Label Period (OL)
Lack of Efficacy
|
0
|
0
|
81
|
|
Open Label Period (OL)
Lost to Follow-up
|
0
|
0
|
27
|
|
Open Label Period (OL)
Withdrawal by Subject
|
0
|
0
|
117
|
|
Open Label Period (OL)
No Longer Meets Study Criteria
|
0
|
0
|
5
|
|
Open Label Period (OL)
Poor/Non-Compliance
|
0
|
0
|
13
|
|
Open Label Period (OL)
Pregnancy
|
0
|
0
|
6
|
|
Open Label Period (OL)
Administrative Reason By Sponsor
|
0
|
0
|
20
|
|
Open Label Period (OL)
Investigator Retiring
|
0
|
0
|
2
|
|
Open Label Period (OL)
Participant Transportation Issues
|
0
|
0
|
1
|
|
Open Label Period (OL)
Participant Relocated
|
0
|
0
|
6
|
|
Open Label Period (OL)
Investigator Dosing the Trial
|
0
|
0
|
1
|
|
Open Label Period (OL)
Site Closure
|
0
|
0
|
3
|
|
Open Label Period (OL)
Trial Terminated
|
0
|
0
|
1
|
|
Open Label Period (OL)
Difficult IV Access with Participant
|
0
|
0
|
1
|
|
Open Label Period (OL)
Patient Decision
|
0
|
0
|
4
|
|
Open Label Period (OL)
Participant Received Wrong Medication
|
0
|
0
|
1
|
|
Open Label Period (OL)
Participant Desires Pregnancy
|
0
|
0
|
2
|
|
Open Label Period (OL)
Participant Missed Consecutive Doses
|
0
|
0
|
5
|
|
Open Label Period (OL)
Medication Lost Efficacy
|
0
|
0
|
1
|
|
Open Label Period (OL)
Investigator Decision
|
0
|
0
|
4
|
|
Open Label Period (OL)
Site Staff Issues
|
0
|
0
|
2
|
|
Open Label Period (OL)
Site Not Participating in Open Label
|
0
|
0
|
9
|
|
Open Label Period (OL)
Participant Surgery
|
0
|
0
|
1
|
Baseline Characteristics
A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Abatacept (ABA)
n=959 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Total
n=1441 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
52.4 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
52.1 years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
52.3 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
789 Participants
n=5 Participants
|
398 Participants
n=7 Participants
|
1187 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
170 Participants
n=5 Participants
|
84 Participants
n=7 Participants
|
254 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Participants, all participants who received at least 1 dose of study medication
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related SAE/AE = possibly, probably, or certainly related to study drug
Outcome measures
| Measure |
Abatacept (ABA)
n=959 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Death
|
5 participants
|
4 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
SAEs
|
123 participants
|
59 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Related SAEs
|
23 participants
|
13 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
SAEs Leading to Discontinuation
|
23 participants
|
7 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
AEs
|
866 participants
|
417 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Related AEs
|
534 participants
|
239 participants
|
|
Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
52 participants
|
20 participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Participants, all participants who received at least 1 dose of study medication
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Outcome measures
| Measure |
Abatacept (ABA)
n=959 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With AEs of Special Interest
Infections/Infestations
|
95 participants
|
40 participants
|
|
DB; Number of Participants With AEs of Special Interest
Serious Infections/Infestations
|
17 participants
|
5 participants
|
|
DB; Number of Participants With AEs of Special Interest
Neoplasms
|
34 participants
|
17 participants
|
|
DB; Number of Participants With AEs of Special Interest
Pre-specified Autoimmune Disorders
|
32 participants
|
15 participants
|
|
DB; Number of Participants With AEs of Special Interest
Pre-specified Acute Infusional AEs
|
96 participants
|
34 participants
|
|
DB; Number of Participants With AEs of Special Interest
Pre-specified Peri-Infusional AEs
|
233 participants
|
98 participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population. One participant in each group was not evaluated for hematology abnormalities due to data unavailability (missing data).
Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): \>3 g/dL decrease from BL; Hematocrit: \<0.75 \* BL; Erythrocytes: \<0.75 \* BL; Platelets (PLT): \<0.67 \* LLN/\>1.5 \* ULN, or if BL \< LLN then use \<0.5 \* BL and \<100,000 mm\^3; Leukocytes: \<0.75 \* LLN/ \>1.25 \* ULN, or if BL\<LLN then use \<0.8 \* BL or \>ULN, or if BL\>ULN then use \>1.2 \* BL or \<LLN; neutrophils+bands: \<1.0 \* 10\^3 c/uL; eosinophils: \>0.750 \* 10\^3 c/uL; basophils: \> 400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750 \* 10\^3 c/uL/ \>7.50 \* 10\^3 c/uL.
Outcome measures
| Measure |
Abatacept (ABA)
n=958 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=481 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low HGB (LLN=1.5%)
|
12 participants
|
14 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low hematocrit (LLN=36%)
|
9 participants
|
12 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low erythrocytes (LLN=3.72-4.27 x10*6 c/uL)
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low PLT (LLN=140-157*10^9 c/L)
|
7 participants
|
3 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High PLT (ULN=415-440*10^9 c/L)
|
2 participants
|
4 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low leukocytes (LLN= 4-9*10^3 c/uL)
|
24 participants
|
12 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High leukocytes (ULN = 10.5-30*10^3 c/uL)
|
70 participants
|
57 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low neutrophils + bands (LLN= 1.5-2.9*10^3 c/uL)
|
16 participants
|
9 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low lymphocytes (LLN= 0.7-2.9*10^3 c/uL)
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High lymphocytes (ULN= 4.5-13.3*10^3 c/uL)
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High monocytes (ULN=1-3.9*10^3 c/uL)
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High basophils (ULN= 0.6*10^3 c/uL)
|
0 participants
|
0 participants
|
|
DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High eosinophils (ULN= 1.5*10^3 c/uL)
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population. Two participants in the ABA group and 3 participants in the PLA group were not evaluated for blood chemistry abnormalities due to data unavailability (missing data).
ULN=upper level of normal; BL=baseline.Marked abnormality criteria: High alkaline phosphatase (ALP): \>2\* ULN, or if BL\>ULN then use \>3\* BL; high aspartate aminotransferase (AST): \>3\* ULN (80 U/L), or if BL\>ULN then use \>4\* BL; high alanine aminotransferase (ALT): \>3\* ULN (34-47 U/L), or if BL\>ULN then use \>4\* BL; high G-Glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN then use \>3\* BL; high bilirubin: \>2\* ULN, or if BL\>ULN then use \>4\* BL; high blood urea nitrogen (BUN): \>2\* BL; high creatinine: \>1.5\* BL (ULN 14.6 pg/mg. AST ULN=80 U/L; ALT ULN=34-47 U/L;creatinine ULN=14.6 pg/mg.
Outcome measures
| Measure |
Abatacept (ABA)
n=957 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=479 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria
High AST (ULN=80 U/L)
|
12 participants
|
3 participants
|
|
DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria
High ALT (ULN=34-47 U/L)
|
16 participants
|
9 participants
|
|
DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria
High creatinine (ULN=14.6 pg/mg)
|
41 participants
|
29 participants
|
PRIMARY outcome
Timeframe: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337. Vital signs were measured at these visits before and after study medication infusion.Population: All Treated Population.
Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
Outcome measures
| Measure |
Abatacept (ABA)
n=959 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 Participants
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 365 to Day 1,821Population: All Treated Participants
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related SAE/AE = possibly, probably, or certainly related to study drug
Outcome measures
| Measure |
Abatacept (ABA)
n=1184 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Death
|
32 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
SAEs
|
425 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Related SAEs
|
124 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
SAEs Leading to Discontinuation
|
70 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
AEs
|
1123 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
Related AEs
|
737 participants
|
—
|
|
Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
103 participants
|
—
|
PRIMARY outcome
Timeframe: Day 365 to Day 1821Population: All Treated Participants, all participants who received at least 1 dose of study medication
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Outcome measures
| Measure |
Abatacept (ABA)
n=1184 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With AEs of Special Interest
Infections/Infestations
|
957 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Total Neoplasms
|
168 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Malignant Neoplasms
|
56 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Benign and Unspecified Neoplasms
|
112 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Pre-specified Autoimmune Disorders
|
67 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Pre-specified Acute Infusional AEs
|
82 participants
|
—
|
|
OL; Number of Participants With AEs of Special Interest
Pre-specified Peri-Infusional AEs
|
219 participants
|
—
|
PRIMARY outcome
Timeframe: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population.
Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): \>3 g/dL decrease from BL; Hematocrit: \<0.75 \* BL; Erythrocytes: \<0.75 \* BL; Platelets (PLT): \<0.67 \* LLN/\>1.5 \* ULN, or if BL \< LLN then use \<0.5 \* BL and \<100,000 mm\^3; Leukocytes: \<0.75 \* LLN/ \>1.25 \* ULN, or if BL\<LLN then use \<0.8 \* BL or \>ULN, or if BL\>ULN then use \>1.2 \* BL or \<LLN; neutrophils+bands: \<1.0 \* 10\^3 c/uL; eosinophils: \>0.750 \* 10\^3 c/uL; basophils: \> 400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750 \* 10\^3 c/uL/ \>7.50 \* 10\^3 c/uL.
Outcome measures
| Measure |
Abatacept (ABA)
n=1184 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low HGB (LLN=1.5%)
|
70 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low hematocrit (LLN=36%)
|
53 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Erythrocytes (LLN=3.72-4.27 x10*6 c/uL)
|
25 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low PLT (LLN=140-157*10^9 c/L)
|
23 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High PLT (ULN=415-440*10^9 c/L)
|
10 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low leukocytes (LLN= 4-9*10^3 c/uL)
|
110 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High leukocytes (ULN = 10.5-30*10^3 c/uL)
|
162 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low neutrophils + bands (LLN= 1.5-2.9*10^3 c/uL)
|
31 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
Low lymphocytes (LLN= 0.7-2.9*10^3 c/uL)
|
220 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High lymphocytes (ULN= 4.5-13.3*10^3 c/uL)
|
5 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High monocytes (ULN=1-3.9*10^3 c/uL)
|
11 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High basophils (ULN= 0.6*10^3 c/uL)
|
4 participants
|
—
|
|
OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
High eosinophils (ULN= 1.5*10^3 c/uL)
|
151 participants
|
—
|
PRIMARY outcome
Timeframe: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population. One participant was not evaluated for liver function abnormalities.
Marked abnormality criteria: Alkaline phosphatase (ALP): \>2\* ULN, or if BL\>ULN then use \>3\* BL; aspartate aminotransferase (AST): \>3\* ULN, or if BL\>ULN then use \>4\* BL; alanine aminotransferase (ALT): \>3\* ULN, or if BL\>ULN then use \>4\* BL; G-Glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN then use \>3\* BL; Bilirubin: \>2\* ULN, or if BL\>ULN then use \>4\* BL; blood urea nitrogen (BUN): \>2\* BL; creatinine: \>1.5\* BL
Outcome measures
| Measure |
Abatacept (ABA)
n=1183 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High ALP (ULN=150 U/L)
|
12 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High AST (ULN=80 U/L)
|
38 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High ALT (ULN=34-47 U/L)
|
54 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High GGT (ULN=43-54 U/L)
|
91 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High bilirubin (ULN=0.3 mg/dL)
|
9 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High BUN (normal=4-25 mg/dL)
|
108 participants
|
—
|
|
OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
High creatinine (ULN=14.6 pg/mg)
|
204 participants
|
—
|
PRIMARY outcome
Timeframe: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population. One participant was not evaluated for electrolyte abnormalities.
Marked abnormality criteria: Sodium (Na): \<0.95\*LLN/ \>1.05\*ULN, or if BL\<LLN then use \<0.95\* BL or \>ULN, or if BL\>ULN then use\>1.05\* BL or \<LLN; potassium (K): \<0.9\* LLN/\>1.1\*ULN, or if BL\<LLN then use \<0.9\* BL or \>ULN, or if BL\>ULN then use\>1.1\* BL or \<LLN; (Cl): \<0.9\* LLN/\>1.1\* ULN, or if BL\<LLN then use \<0.9\* BL or \>ULN, or if BL\>ULN then use\>1.1\* BL or \<LLN; calcium (Ca): \<0.8\* LLN/\>1.2\* ULN, or if BL\<LLN then use \<0.75\* BL or \>ULN, or if BL\>ULN then use\>1.25\* BL or \<LLN; phosphorous (P): \<0.75\* LLN/ \>1.25\* ULN, or if BL\<LLN then use 0.67\* BL or \>ULN, or if BL\>ULN then use\>1.33\* BL or \<LLN
Outcome measures
| Measure |
Abatacept (ABA)
n=1183 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
Low Na (LLN=135 mEq/L)
|
16 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
High Na (ULN=148 mEq/L)
|
1 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
Low K (LLN=3.5 mEq/L)
|
77 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
High K (ULN=5.5 mEq/L)
|
72 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
Low Cl (LLN= 96 mEq/L)
|
5 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
High Cl (ULN=109 mEq/L)
|
2 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
Low Ca (LLN=8.5 mg/dL)
|
2 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
High Ca (ULN=11 mg/dL)
|
0 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
Low P (LLN=2.5 mg/dL)
|
17 participants
|
—
|
|
OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
High P (ULN 7.1 mg/dL)
|
27 participants
|
—
|
PRIMARY outcome
Timeframe: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medicationPopulation: All Treated Population. N=Number of Participants Analyzed, n=number of participants with measurements at time point
MA criteria: serum glucose (Glu): \<65 mg/dL/\>220 mg/dL;fasting serum Glu: \<0.8\* LLN/\>1.5\*ULN,or if BL\<LLN then use 0.8\*BL or \>ULN,or if BL\>ULN then use \>2.0\*BL or \<LLN;total protein: \<0.9\*LLN/\>1.1\*ULN,or if BL\<LLN then use \<0.9\*BL or \>UNL,or if BL\>UNL then use \>1.1\*BL or \<LLN; albumin: \<0.9\*LLN,or if BL\<LLN then use \<0.75 BL;uric acid: \>1.5\*ULN,or if BL\>ULN then use \>2\*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells \[RBCs\], White Blood Cells \[WBCs\]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Outcome measures
| Measure |
Abatacept (ABA)
n=1184 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
Low Glu, n=1184
|
207 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High Glu, n=1184
|
61 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
Low fasting Glu, n=647 (LLN=65 mg/dL)
|
647 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High fasting Glu, n=647 (ULN=115 mg/dL)
|
41 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
Low protein, n=1183 (LLN=6 g/dL)
|
12 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High protein, n=1183 (ULN=8.5 g/dL)
|
2 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
Low albumin, n=1183 (LLN=3.5 g/dL)
|
40 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High uric acid, n=1183 (ULN=8.7 mg/dL)
|
19 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine protein, n=1184 (normal=trace)
|
125 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine glucose, n=1184 (normal=negative)
|
51 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine ketones, n=33 (normal=negative)
|
0 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine blood, n=1184 (normal=negative)
|
310 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High leukocyte esterase, n=32
|
12 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine WBC, n=852
|
429 participants
|
—
|
|
OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
High urine RBC, n=852
|
403 participants
|
—
|
PRIMARY outcome
Timeframe: Days 365 to Day 1821Population: All Treated Population.
Physical examinations were performed at the discretion of the investigator and included breast examinations for female participants. Vital sign measurements were performed for participants before and after infusion of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
Outcome measures
| Measure |
Abatacept (ABA)
n=1184 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Days 1, 29, 57, 85, 113,169, 281, 365Population: All participants treated during DB who received at least 1 dose of abatacept and had antibody samples collected at baseline and at least 1 post-baseline visit. 561 participants were not evaluated for anti-abatacept anti-bodies during the DB.
Serum samples from all treated adult participants with active rheumatoid arthritis (RA) were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Outcome measures
| Measure |
Abatacept (ABA)
n=880 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
Anti-abatacept antibodies
|
13 participants
|
—
|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
Anti-CTLA4 antibodies
|
9 participants
|
—
|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
Total antibodies
|
22 participants
|
—
|
SECONDARY outcome
Timeframe: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337Population: All DB participants treated on study who received at least 1 dose of abatacept and had antibody samples collected at baseline and at least 1 post-baseline visit. 68 participants were not evaluated for anti-abatacept anti-bodies on study.
Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Outcome measures
| Measure |
Abatacept (ABA)
n=1296 Participants
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants \< 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
Anti-abatacept antibodies (n=1228)
|
66 participants
|
—
|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
Anti-CTLA4 antibodies (n=1296)
|
48 participants
|
—
|
|
DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
Total antibodies (n=1296)
|
107 participants
|
—
|
Adverse Events
Open Label (OL) Abatacept
Serious events: 425 serious events
Other events: 1010 other events
Deaths: 0 deaths
Abatacept (ABA)
Serious events: 124 serious events
Other events: 715 other events
Deaths: 0 deaths
Placebo (PLA)
Serious events: 59 serious events
Other events: 346 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open Label (OL) Abatacept
n=1184 participants at risk
Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
|
Abatacept (ABA)
n=959 participants at risk
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for subjects \< 60 kg, 750 mg for subjects 60 to 100 kg and 1 g for subjects \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 participants at risk
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|---|
|
Eye disorders
CATARACT
|
0.08%
1/1184
|
0.10%
1/959
|
0.41%
2/482
|
|
Eye disorders
PTERYGIUM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Eye disorders
SCLEROMALACIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Investigations
HIV TEST POSITIVE
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Investigations
HAEMATOCRIT DECREASED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Investigations
BLOOD GLUCOSE INCREASED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Investigations
TRANSAMINASES INCREASED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Investigations
ELECTROCARDIOGRAM CHANGE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Investigations
HEPATIC ENZYME INCREASED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Investigations
ELECTROCARDIOGRAM ST-T SEGMENT ABNORMAL
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ARRHYTHMIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
BRADYCARDIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Cardiac disorders
TACHYCARDIA
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
PERICARDITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ATRIAL FLUTTER
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
CARDIAC ARREST
|
0.25%
3/1184
|
0.21%
2/959
|
0.21%
1/482
|
|
Cardiac disorders
CARDIOMYOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ANGINA PECTORIS
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.42%
5/1184
|
0.00%
0/959
|
0.41%
2/482
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
CARDIAC TAMPONADE
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
CARDIOGENIC SHOCK
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.34%
4/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
SICK SINUS SYNDROME
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
AORTIC VALVE DISEASE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
MITRAL VALVE STENOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
1.2%
14/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
ACUTE CORONARY SYNDROME
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
CORONARY ARTERY DISEASE
|
0.51%
6/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
CORONARY ARTERY STENOSIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
HEART VALVE INCOMPETENCE
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
ISCHAEMIC CARDIOMYOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
CONGESTIVE CARDIOMYOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
CORONARY ARTERY OCCLUSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
MITRAL VALVE INCOMPETENCE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.59%
7/1184
|
0.21%
2/959
|
0.41%
2/482
|
|
Cardiac disorders
HYPERTENSIVE HEART DISEASE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
0.59%
7/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Cardiac disorders
ATRIOVENTRICULAR BLOCK COMPLETE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Cardiac disorders
ARTERIOSCLEROSIS CORONARY ARTERY
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Vascular disorders
HYPOTENSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
HYPERTENSION
|
0.34%
4/1184
|
0.10%
1/959
|
0.41%
2/482
|
|
Vascular disorders
AORTIC ANEURYSM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
AORTIC STENOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
ARTERIOSCLEROSIS
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Vascular disorders
AORTIC DISSECTION
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Vascular disorders
ARTERIAL STENOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
VENOUS THROMBOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
EXTREMITY NECROSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
VASCULAR OCCLUSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
HYPERTENSIVE CRISIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
0.34%
4/1184
|
0.31%
3/959
|
0.21%
1/482
|
|
Vascular disorders
ILIAC ARTERY EMBOLISM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
RHEUMATOID VASCULITIS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Vascular disorders
VENOUS THROMBOSIS LIMB
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
AXILLARY VEIN THROMBOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
PERIPHERAL VASCULAR DISORDER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
THROMBOPHLEBITIS SUPERFICIAL
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Vascular disorders
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Endocrine disorders
HYPERTHYROIDISM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Social circumstances
VICTIM OF HOMICIDE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Psychiatric disorders
ANXIETY
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Psychiatric disorders
DEPRESSION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Psychiatric disorders
SUICIDE ATTEMPT
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Psychiatric disorders
BIPOLAR DISORDER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Psychiatric disorders
MAJOR DEPRESSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
HEPATITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
CHOLANGITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
HEPATIC MASS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
LIVER INJURY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
BILIARY COLIC
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.76%
9/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
0.84%
10/1184
|
0.31%
3/959
|
0.62%
3/482
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Immune system disorders
ANAPHYLACTIC REACTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
SYNCOPE
|
0.34%
4/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Nervous system disorders
HEADACHE
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Nervous system disorders
MIGRAINE
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Nervous system disorders
SCIATICA
|
0.42%
5/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
NEURALGIA
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
PRESYNCOPE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
PARAESTHESIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
HYPOAESTHESIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Nervous system disorders
RADICULOPATHY
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Nervous system disorders
ENCEPHALOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
POLYNEUROPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
ISCHAEMIC STROKE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
MOYAMOYA DISEASE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
NERVE COMPRESSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
CEREBRAL ISCHAEMIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
CERVICAL MYELOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
SPINAL CLAUDICATION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
LOSS OF CONSCIOUSNESS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
NEUROPATHY PERIPHERAL
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
CARPAL TUNNEL SYNDROME
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Nervous system disorders
NERVE ROOT COMPRESSION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
CAROTID ARTERY STENOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Nervous system disorders
CEREBROVASCULAR ACCIDENT
|
0.25%
3/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
Nervous system disorders
CEREBROVASCULAR DISORDER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
SUBARACHNOID HAEMORRHAGE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
RUPTURED CEREBRAL ANEURYSM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.34%
4/1184
|
0.21%
2/959
|
0.21%
1/482
|
|
Nervous system disorders
COMPLEX REGIONAL PAIN SYNDROME
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
NAUSEA
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
COLITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Gastrointestinal disorders
VOMITING
|
0.17%
2/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
FAECALOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
GASTRITIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
GINGIVITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ANAL FISSURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Gastrointestinal disorders
DIVERTICULUM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
OESOPHAGITIS
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
COLONIC ATONY
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
GASTRIC ULCER
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.59%
7/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.42%
5/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ABDOMINAL HERNIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
UMBILICAL HERNIA
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
COLITIS ISCHAEMIC
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
GASTRITIS EROSIVE
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
OESOPHAGEAL SPASM
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
OESOPHAGEAL ULCER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
PANCREATITIS ACUTE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
INTESTINAL ISCHAEMIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
DIVERTICULAR PERFORATION
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
IRRITABLE BOWEL SYNDROME
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
MESENTERIC ARTERY EMBOLISM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
LARGE INTESTINE PERFORATION
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
ABDOMINAL HERNIA OBSTRUCTIVE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.17%
2/1184
|
0.00%
0/959
|
0.62%
3/482
|
|
Gastrointestinal disorders
SMALL INTESTINAL OBSTRUCTION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
LOWER GASTROINTESTINAL HAEMORRHAGE
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Ear and labyrinth disorders
SUDDEN HEARING LOSS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Ear and labyrinth disorders
DEAFNESS NEUROSENSORY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Ear and labyrinth disorders
NEUROSENSORY HYPOACUSIS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
SEPSIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
ABSCESS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
EMPYEMA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
INFLUENZA
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
PNEUMONIA
|
1.0%
12/1184
|
0.42%
4/959
|
0.62%
3/482
|
|
Infections and infestations
SINUSITIS
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
UROSEPSIS
|
0.25%
3/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
BRONCHITIS
|
0.84%
10/1184
|
0.31%
3/959
|
0.00%
0/482
|
|
Infections and infestations
CELLULITIS
|
0.51%
6/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
Infections and infestations
CERVICITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
ERYSIPELAS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BACTERAEMIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
CANDIDIASIS
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Infections and infestations
HEPATITIS E
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
ABSCESS LIMB
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
APPENDICITIS
|
0.42%
5/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BONE ABSCESS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
EPIGLOTTITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
OTITIS MEDIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
SEPTIC SHOCK
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
ASPERGILLOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
HERPES ZOSTER
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
OSTEOMYELITIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
TOOTH ABSCESS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
BRONCHIECTASIS
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
DIVERTICULITIS
|
0.51%
6/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
HERPES SIMPLEX
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
LUNG INFECTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PYELONEPHRITIS
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
GASTROENTERITIS
|
0.51%
6/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
LOBAR PNEUMONIA
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
VIRAL INFECTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
WOUND INFECTION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BRONCHOPNEUMONIA
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
SYSTEMIC MYCOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BONE TUBERCULOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
CANDIDA PNEUMONIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
CHRONIC SINUSITIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BURSITIS INFECTIVE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
ESCHERICHIA SEPSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
HUMAN EHRLICHIOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PERIRECTAL ABSCESS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
ARTHRITIS BACTERIAL
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BACTERIAL INFECTION
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Infections and infestations
HAEMATOMA INFECTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
INFECTED SKIN ULCER
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
LOCALISED INFECTION
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
DIARRHOEA INFECTIOUS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PYELONEPHRITIS ACUTE
|
0.51%
6/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Infections and infestations
SUBCUTANEOUS ABSCESS
|
0.08%
1/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Infections and infestations
OSTEOMYELITIS CHRONIC
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PERITONSILLAR ABSCESS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PNEUMONIA HAEMOPHILUS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
STAPHYLOCOCCAL SEPSIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PNEUMONIA PNEUMOCOCCAL
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
RESPIRATORY MONILIASIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
LYMPH NODE TUBERCULOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PNEUMONIA STREPTOCOCCAL
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.51%
6/1184
|
0.21%
2/959
|
0.21%
1/482
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
INCISION SITE CELLULITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
CELLULITIS STAPHYLOCOCCAL
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
POST PROCEDURAL INFECTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
STREPTOCOCCAL BACTERAEMIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
GASTROENTERITIS SALMONELLA
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Infections and infestations
GASTROINTESTINAL INFECTION
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Infections and infestations
STAPHYLOCOCCAL BACTERAEMIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PELVIC INFLAMMATORY DISEASE
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Infections and infestations
STAPHYLOCOCCAL OSTEOMYELITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
CLOSTRIDIUM DIFFICILE COLITIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
POSTOPERATIVE WOUND INFECTION
|
0.42%
5/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
BRONCHOPULMONARY ASPERGILLOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Infections and infestations
PNEUMOCYSTIS JIROVECI PNEUMONIA
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
RENAL INFARCT
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
CALCULUS URETERIC
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Renal and urinary disorders
RENAL AMYLOIDOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
GLOMERULONEPHRITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.42%
5/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Renal and urinary disorders
URINARY INCONTINENCE
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Renal and urinary disorders
STRESS URINARY INCONTINENCE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Metabolism and nutrition disorders
OBESITY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS INADEQUATE CONTROL
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.25%
3/1184
|
0.21%
2/959
|
0.41%
2/482
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
LYMPHADENITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
LYMPHADENOPATHY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
BONE MARROW FAILURE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Blood and lymphatic system disorders
BONE MARROW TOXICITY
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Skin and subcutaneous tissue disorders
PANNICULITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Skin and subcutaneous tissue disorders
SKIN FISSURES
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Skin and subcutaneous tissue disorders
DECUBITUS ULCER
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Skin and subcutaneous tissue disorders
LICHENOID KERATOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Skin and subcutaneous tissue disorders
PYODERMA GANGRENOSUM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Skin and subcutaneous tissue disorders
DERMATITIS PSORIASIFORM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
CYSTOCELE
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
ADENOMYOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
METRORRHAGIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Reproductive system and breast disorders
OVARIAN CYST
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
ENDOMETRIOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
GYNAECOMASTIA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
CERVICAL POLYP
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
BREAST DISORDER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
MENOMETRORRHAGIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
UTERINE PROLAPSE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
UTERINE HAEMORRHAGE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
FIBROCYSTIC BREAST DISEASE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Reproductive system and breast disorders
BENIGN PROSTATIC HYPERPLASIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Congenital, familial and genetic disorders
CONGENITAL CEREBRAL CYST
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FALL
|
0.34%
4/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
OVERDOSE
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
POISONING
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
UNDERDOSE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
LIMB INJURY
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
HIP FRACTURE
|
0.68%
8/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
RIB FRACTURE
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FOOT FRACTURE
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
ANKLE FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
DEVICE FAILURE
|
0.25%
3/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
TENDON RUPTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
WRIST FRACTURE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FIBULA FRACTURE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
PELVIC FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
PROCEDURAL PAIN
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
SKIN LACERATION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
STRESS FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FOREARM FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
HUMERUS FRACTURE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
MEDICATION ERROR
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
WOUND DEHISCENCE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
CLAVICLE FRACTURE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
JOINT DISLOCATION
|
0.17%
2/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
Injury, poisoning and procedural complications
BURNS THIRD DEGREE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
DEVICE DISLOCATION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
0.25%
3/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
PUBIC RAMI FRACTURE
|
0.08%
1/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
LIMB CRUSHING INJURY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FACIAL BONES FRACTURE
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
FEMORAL NECK FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
TRAUMATIC LIVER INJURY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
DISLOCATION OF VERTEBRA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
DRUG ADMINISTRATION ERROR
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
THERAPEUTIC AGENT TOXICITY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
INCORRECT DOSE ADMINISTERED
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
MEDICAL DEVICE COMPLICATION
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
SPINAL COMPRESSION FRACTURE
|
0.17%
2/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
SUTURE RELATED COMPLICATION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
POST PROCEDURAL COMPLICATION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Injury, poisoning and procedural complications
DISLOCATION OF JOINT PROSTHESIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Pregnancy, puerperium and perinatal conditions
ABORTION SPONTANEOUS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
BURSITIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
ARTHRITIS
|
0.84%
10/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.42%
5/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Musculoskeletal and connective tissue disorders
SYNOVITIS
|
0.34%
4/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.42%
5/1184
|
0.10%
1/959
|
0.41%
2/482
|
|
Musculoskeletal and connective tissue disorders
FLANK PAIN
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
ARTHROPATHY
|
0.08%
1/1184
|
0.10%
1/959
|
0.62%
3/482
|
|
Musculoskeletal and connective tissue disorders
BONE EROSION
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
OSTEOPOROSIS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
OSTEONECROSIS
|
0.34%
4/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
FOOT DEFORMITY
|
0.68%
8/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
HAND DEFORMITY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
2.3%
27/1184
|
0.31%
3/959
|
0.41%
2/482
|
|
Musculoskeletal and connective tissue disorders
COSTOCHONDRITIS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
JOINT ANKYLOSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
FINGER DEFORMITY
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
JOINT DESTRUCTION
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.17%
2/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID NODULE
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS
|
4.7%
56/1184
|
2.2%
21/959
|
1.9%
9/482
|
|
Musculoskeletal and connective tissue disorders
OSTEOPOROTIC FRACTURE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
ROTATOR CUFF SYNDROME
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
SPINAL OSTEOARTHRITIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
LUMBAR SPINAL STENOSIS
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL CHEST PAIN
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL DISCOMFORT
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC DISORDER
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
SYSTEMIC LUPUS ERYTHEMATOSUS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
0.59%
7/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC DEGENERATION
|
0.25%
3/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.17%
2/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.08%
1/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
LUNG DISORDER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
PLEURITIC PAIN
|
0.17%
2/1184
|
0.00%
0/959
|
0.21%
1/482
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHIAL POLYP
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
RHEUMATOID LUNG
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.17%
2/1184
|
0.21%
2/959
|
0.21%
1/482
|
|
Respiratory, thoracic and mediastinal disorders
TRACHEAL STENOSIS
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
BRONCHITIS CHRONIC
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY FIBROSIS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
STATUS ASTHMATICUS
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.34%
4/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
NASAL SEPTUM DEVIATION
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
|
0.17%
2/1184
|
0.31%
3/959
|
0.00%
0/482
|
|
General disorders
DEATH
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
General disorders
HERNIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
General disorders
FATIGUE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
General disorders
MALAISE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
General disorders
PYREXIA
|
0.34%
4/1184
|
0.10%
1/959
|
0.21%
1/482
|
|
General disorders
ASTHENIA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
General disorders
CHEST PAIN
|
1.1%
13/1184
|
0.42%
4/959
|
0.62%
3/482
|
|
General disorders
HYPERTHERMIA
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
General disorders
IMPAIRED HEALING
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
General disorders
HERNIA OBSTRUCTIVE
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LIPOMA
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OSTEOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEIOMYOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
|
0.51%
6/1184
|
0.10%
1/959
|
0.41%
2/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON ADENOMA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOMA BENIGN
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
GASTRIC CANCER
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEIOMYOSARCOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
THYROID CANCER
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BOWEN'S DISEASE
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
KAPOSI'S SARCOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.17%
2/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ENDOMETRIAL CANCER
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SEBACEOUS CARCINOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
|
1.3%
15/1184
|
0.52%
5/959
|
0.62%
3/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PANCREATIC CARCINOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CELL CARCINOMA
|
0.00%
0/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER IN SITU
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG CANCER METASTATIC
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-HODGKIN'S LYMPHOMA
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT
|
0.00%
0/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PITUITARY TUMOUR BENIGN
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA
|
0.59%
7/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELODYSPLASTIC SYNDROME
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CERVIX CARCINOMA STAGE II
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT MELANOMA IN SITU
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-SMALL CELL LUNG CANCER
|
0.08%
1/1184
|
0.10%
1/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF SKIN
|
0.76%
9/1184
|
0.21%
2/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SQUAMOUS CELL CARCINOMA OF THE CERVIX
|
0.17%
2/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SMALL CELL LUNG CANCER STAGE UNSPECIFIED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT TYPE)
|
0.08%
1/1184
|
0.00%
0/959
|
0.00%
0/482
|
Other adverse events
| Measure |
Open Label (OL) Abatacept
n=1184 participants at risk
Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
|
Abatacept (ABA)
n=959 participants at risk
Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for subjects \< 60 kg, 750 mg for subjects 60 to 100 kg and 1 g for subjects \> 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
Placebo (PLA)
n=482 participants at risk
Participants received Placebo (dextrose 5% water \[D5W\] for injection U.S.P or normal saline \[NS\]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs \[DMARDs\], or combination) throughout the double-blind treatment period.
|
|---|---|---|---|
|
Eye disorders
CONJUNCTIVITIS
|
6.1%
72/1184
|
2.3%
22/959
|
2.3%
11/482
|
|
Vascular disorders
HYPERTENSION
|
13.7%
162/1184
|
7.1%
68/959
|
5.0%
24/482
|
|
Psychiatric disorders
INSOMNIA
|
8.1%
96/1184
|
4.5%
43/959
|
2.9%
14/482
|
|
Psychiatric disorders
DEPRESSION
|
6.4%
76/1184
|
3.9%
37/959
|
2.7%
13/482
|
|
Nervous system disorders
HEADACHE
|
18.2%
216/1184
|
20.3%
195/959
|
14.3%
69/482
|
|
Nervous system disorders
DIZZINESS
|
11.4%
135/1184
|
10.9%
105/959
|
8.9%
43/482
|
|
Gastrointestinal disorders
NAUSEA
|
13.0%
154/1184
|
12.6%
121/959
|
11.6%
56/482
|
|
Gastrointestinal disorders
VOMITING
|
8.5%
101/1184
|
6.0%
58/959
|
5.6%
27/482
|
|
Gastrointestinal disorders
DIARRHOEA
|
15.7%
186/1184
|
10.0%
96/959
|
12.0%
58/482
|
|
Gastrointestinal disorders
DYSPEPSIA
|
9.5%
112/1184
|
7.5%
72/959
|
5.0%
24/482
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
8.1%
96/1184
|
3.6%
35/959
|
3.3%
16/482
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
8.5%
101/1184
|
4.6%
44/959
|
3.7%
18/482
|
|
Infections and infestations
RHINITIS
|
5.7%
67/1184
|
2.9%
28/959
|
1.5%
7/482
|
|
Infections and infestations
INFLUENZA
|
12.2%
145/1184
|
6.3%
60/959
|
6.2%
30/482
|
|
Infections and infestations
SINUSITIS
|
16.7%
198/1184
|
6.9%
66/959
|
7.3%
35/482
|
|
Infections and infestations
BRONCHITIS
|
19.3%
229/1184
|
5.4%
52/959
|
5.2%
25/482
|
|
Infections and infestations
PHARYNGITIS
|
7.6%
90/1184
|
2.3%
22/959
|
2.5%
12/482
|
|
Infections and infestations
GASTROENTERITIS
|
7.3%
87/1184
|
1.5%
14/959
|
1.5%
7/482
|
|
Infections and infestations
NASOPHARYNGITIS
|
22.5%
266/1184
|
10.2%
98/959
|
9.5%
46/482
|
|
Infections and infestations
URINARY TRACT INFECTION
|
16.5%
195/1184
|
8.1%
78/959
|
4.8%
23/482
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
30.6%
362/1184
|
14.9%
143/959
|
15.4%
74/482
|
|
Blood and lymphatic system disorders
ANAEMIA
|
5.5%
65/1184
|
1.9%
18/959
|
2.9%
14/482
|
|
Skin and subcutaneous tissue disorders
RASH
|
7.2%
85/1184
|
4.7%
45/959
|
3.9%
19/482
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
5.8%
69/1184
|
3.4%
33/959
|
3.9%
19/482
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
17.7%
210/1184
|
7.1%
68/959
|
5.8%
28/482
|
|
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS
|
5.9%
70/1184
|
2.2%
21/959
|
2.7%
13/482
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
16.5%
195/1184
|
8.8%
84/959
|
7.7%
37/482
|
|
Respiratory, thoracic and mediastinal disorders
RHINITIS ALLERGIC
|
6.5%
77/1184
|
1.9%
18/959
|
1.0%
5/482
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
6.8%
80/1184
|
3.1%
30/959
|
5.2%
25/482
|
|
General disorders
FATIGUE
|
5.3%
63/1184
|
6.8%
65/959
|
5.2%
25/482
|
|
General disorders
PYREXIA
|
5.5%
65/1184
|
3.9%
37/959
|
3.7%
18/482
|
|
General disorders
CHEST PAIN
|
6.2%
73/1184
|
2.7%
26/959
|
2.3%
11/482
|
|
General disorders
OEDEMA PERIPHERAL
|
7.0%
83/1184
|
3.6%
35/959
|
6.4%
31/482
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER