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A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00048932
Collaborator
(none)
1,795
Enrollment
44
Locations
3
Arms
82
Duration (Months)
40.8
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn if abatacept is safe when co-administered with other approved rheumatoid arthritis medications.

Condition or Disease Intervention/Treatment Phase
  • Drug: Double-blind Abatacept
  • Drug: Double-blind Placebo
  • Drug: Open-label Abatacept
 Phase 3

Detailed Description

This was a multinational, multicenter, randomized, double-blind, 2-arm, parallel-dosing designed study. The treatment period was 12 months. Eligible participants were randomized to 1 of 2 treatment groups: abatacept fixed dose approximating 10 mg/kg (based on participant's body weight; 500 mg for participants weighing < 60kg; 750 mg for participants weighing 60 to 100 kg; and 1 gram for participants weighing > 100 kg, monthly) or placebo intravenous (IV) infusion. All participants continued their 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 study medication (abatacept or placebo) was administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses.

All participants who completed the 12-month double-blind study period (Day 1 through Day 365), were eligible to continue into the open-label period. All eligible participants (active or placebo) were re-allocated to receive abatacept at a weight-tiered dose that approximated 10 mg/kg, based on their Day 365 body weight. Participants continued to receive infusions every 28 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
1795 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Study Start Date :
Dec 1, 2002
Actual Primary Completion Date :
Oct 1, 2009
Actual Study Completion Date :
Oct 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Double-blind abatacept

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

Drug: Double-blind Abatacept
Concentrate and diluted in a solution, IV, 500 mg (body weight < 60 Kg); 750 mg (body weight 60-100 Kg); 1000 mg (body weight > 100 Kg), Once daily, Day 1, 15, and 29.
Other Names:
  • Orencia
  • BMS-188667

    		•
    Placebo Comparator: Double-blind Placebo

    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.

    Drug: Double-blind Placebo
    Concentrate and diluted in a solution, IV, 0 mg, Once daily, Day 1, 15, and 29.
    Active Comparator: Open-label Abatacept

    Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.

    Drug: Open-label Abatacept
    Concentrate and diluted in a solution, IV, 500 mg (body weight < 60 Kg); 750 mg (body weight 60-100 Kg); 1000 mg (body weight > 100 Kg), Once daily, Every 28 days.
    Other Names:
  • Orencia
  • BMS-188667

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 [Day 1 to Day 365, and including data up to 56 days post last dose of double-blind 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

    2. DB; Number of Participants With AEs of Special Interest [Day 1 to Day 365, and including data up to 56 days post last dose of double-blind 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).

    3. DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication]

      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.

    4. DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria [Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication]

      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.

    5. DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [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.]

      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.

    6. 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 [Day 365 to Day 1,821]

      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

    7. OL; Number of Participants With AEs of Special Interest [Day 365 to Day 1821]

      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).

    8. OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication]

      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.

    9. OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria [Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication]

      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

    10. OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria [Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication]

      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

    11. OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria [Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication]

      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

    12. OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [Days 365 to Day 1821]

      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.

    Secondary Outcome Measures

    1. DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA) [Days 1, 29, 57, 85, 113,169, 281, 365]

      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.

    2. DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA [Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Meet criteria of American Rheumatism Association for the diagnosis of rheumatoid arthritis and the American College of Rheumatology functional classes I, II III or IV

    • Participants must be taking 1 or more DMARDs and/or biologic approved for rheumatoid arthritis (RA) for at least 3 months and be on a stable dose for 28 days prior to Day

    Exclusion:

    • Other auto-immune disease as a main diagnosis (e.g. Systemic Lupus Erythematosus [SLE], Scleroderma)

    • Active tuberculosis (TB) requiring treatment within last 3 years

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution Decatur Alabama United States
    2 Local Institution Paradise Arizona United States
    3 Local Institution Phoenix Arizona United States
    4 Local Institution Tucson Arizona United States
    5 Local Institution San Francisco California United States
    6 Local Institution Loveland Colorado United States
    7 Local Institution Hamden Connecticut United States
    8 Local Institution Lake Worth Florida United States
    9 Local Institution Largo Florida United States
    10 Local Institution Blairsville Georgia United States
    11 Local Institution Chicago Illinois United States
    12 Local Institution Evansville Indiana United States
    13 Local Institution Indianapolis Indiana United States
    14 Local Institution Wichita Kansas United States
    15 Local Institution Louisville Kentucky United States
    16 Local Institution New Orleans Louisiana United States
    17 Local Institution Baltimore Maryland United States
    18 Local Institution Cumberland Maryland United States
    19 Local Institution Westminster Maryland United States
    20 Local Institution Boston Massachusetts United States
    21 Local Institution Grand Rapids Michigan United States
    22 Local Institution Royal Oak Michigan United States
    23 Local Institution Toms River New Jersey United States
    24 Local Institution Los Alamos New Mexico United States
    25 Local Institution New York New York United States
    26 Local Institution Durham North Carolina United States
    27 Local Institution Hickory North Carolina United States
    28 Local Institution Canton Ohio United States
    29 Local Institution Cleveland Ohio United States
    30 Local Institution Columbus Ohio United States
    31 Local Institution Elyria Ohio United States
    32 Local Institution Youngstown Ohio United States
    33 Local Institution Oklahoma City Oklahoma United States
    34 Local Institution Wyomissing Pennsylvania United States
    35 Local Institution Columbia South Carolina United States
    36 Local Institution Sioux Falls South Dakota United States
    37 Local Institution Ducktown Tennessee United States
    38 Local Institution Nashville Tennessee United States
    39 Local Institution Richmond Virginia United States
    40 Local Institution Edmonds Washington United States
    41 Local Institution Olympia Washington United States
    42 Local Institution Tacoma Washington United States
    43 Local Institution Menomonee Falls Wisconsin United States
    44 Local Institution Milwaukee Wisconsin United States

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00048932
    Other Study ID Numbers:
    • IM101-031
    First Posted:
    Nov 13, 2002
    Last Update Posted:
    Nov 24, 2011
    Last Verified:
    Nov 1, 2011
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Abatacept

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title Abatacept (ABA) Placebo (PLA) Open Label (OL) Abatacept
    Arm/Group Description 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. 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. Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Period Title: Double Blind Period (DB)
    STARTED 959 482 0
    COMPLETED 836 395 0
    NOT COMPLETED 123 87 0
    Period Title: Double Blind Period (DB)
    STARTED 0 0 1184
    COMPLETED 0 0 743
    NOT COMPLETED 0 0 441

    Baseline Characteristics

    Arm/Group Title Abatacept (ABA) Placebo (PLA) Total
    Arm/Group Description 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. 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 of all reporting groups
    Overall Participants 959 482 1441
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.4
    (11.7)
    52.1
    (12.0)
    52.3
    (11.8)
    Sex: Female, Male (Count of Participants)
    Female
    789
    82.3%
    398
    82.6%
    1187
    82.4%
    Male
    170
    17.7%
    84
    17.4%
    254
    17.6%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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
    Time Frame Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants, all participants who received at least 1 dose of study medication
    Arm/Group Title Abatacept (ABA) Placebo (PLA)
    Arm/Group Description 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. 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.
    Measure Participants 959 482
    Death
    5
    0.5%
    4
    0.8%
    SAEs
    123
    12.8%
    59
    12.2%
    Related SAEs
    23
    2.4%
    13
    2.7%
    SAEs Leading to Discontinuation
    23
    2.4%
    7
    1.5%
    AEs
    866
    90.3%
    417
    86.5%
    Related AEs
    534
    55.7%
    239
    49.6%
    AEs Leading to Discontinuation
    52
    5.4%
    20
    4.1%
    2. Primary Outcome
    Title DB; Number of Participants With AEs of Special Interest
    Description 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).
    Time Frame Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants, all participants who received at least 1 dose of study medication
    Arm/Group Title Abatacept (ABA) Placebo (PLA)
    Arm/Group Description 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. 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.
    Measure Participants 959 482
    Infections/Infestations
    95
    9.9%
    40
    8.3%
    Serious Infections/Infestations
    17
    1.8%
    5
    1%
    Neoplasms
    34
    3.5%
    17
    3.5%
    Pre-specified Autoimmune Disorders
    32
    3.3%
    15
    3.1%
    Pre-specified Acute Infusional AEs
    96
    10%
    34
    7.1%
    Pre-specified Peri-Infusional AEs
    233
    24.3%
    98
    20.3%
    3. Primary Outcome
    Title DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
    Description 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.
    Time Frame Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Population. One participant in each group was not evaluated for hematology abnormalities due to data unavailability (missing data).
    Arm/Group Title Abatacept (ABA) Placebo (PLA)
    Arm/Group Description 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. 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.
    Measure Participants 958 481
    Low HGB (LLN=1.5%)
    12
    1.3%
    14
    2.9%
    Low hematocrit (LLN=36%)
    9
    0.9%
    12
    2.5%
    Low erythrocytes (LLN=3.72-4.27 x10*6 c/uL)
    0
    0%
    0
    0%
    Low PLT (LLN=140-157*10^9 c/L)
    7
    0.7%
    3
    0.6%
    High PLT (ULN=415-440*10^9 c/L)
    2
    0.2%
    4
    0.8%
    Low leukocytes (LLN= 4-9*10^3 c/uL)
    24
    2.5%
    12
    2.5%
    High leukocytes (ULN = 10.5-30*10^3 c/uL)
    70
    7.3%
    57
    11.8%
    Low neutrophils + bands (LLN= 1.5-2.9*10^3 c/uL)
    16
    1.7%
    9
    1.9%
    Low lymphocytes (LLN= 0.7-2.9*10^3 c/uL)
    0
    0%
    0
    0%
    High lymphocytes (ULN= 4.5-13.3*10^3 c/uL)
    0
    0%
    0
    0%
    High monocytes (ULN=1-3.9*10^3 c/uL)
    0
    0%
    0
    0%
    High basophils (ULN= 0.6*10^3 c/uL)
    0
    0%
    0
    0%
    High eosinophils (ULN= 1.5*10^3 c/uL)
    0
    0%
    0
    0%
    4. Primary Outcome
    Title DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria
    Description 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.
    Time Frame Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    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).
    Arm/Group Title Abatacept (ABA) Placebo (PLA)
    Arm/Group Description 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. 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.
    Measure Participants 957 479
    High AST (ULN=80 U/L)
    12
    1.3%
    3
    0.6%
    High ALT (ULN=34-47 U/L)
    16
    1.7%
    9
    1.9%
    High creatinine (ULN=14.6 pg/mg)
    41
    4.3%
    29
    6%
    5. Secondary Outcome
    Title DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
    Description 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.
    Time Frame Days 1, 29, 57, 85, 113,169, 281, 365

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title All Treated Participants
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 880
    Anti-abatacept antibodies
    13
    1.4%
    Anti-CTLA4 antibodies
    9
    0.9%
    Total antibodies
    22
    2.3%
    6. Primary Outcome
    Title DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
    Description 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.
    Time Frame 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.

    Outcome Measure Data

    Analysis Population Description
    All Treated Population.
    Arm/Group Title Abatacept (ABA) Placebo (PLA)
    Arm/Group Description 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. 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.
    Measure Participants 959 482
    Number [participants]
    0
    0%
    0
    0%
    7. Primary Outcome
    Title 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
    Description 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
    Time Frame Day 365 to Day 1,821

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1184
    Death
    32
    3.3%
    SAEs
    425
    44.3%
    Related SAEs
    124
    12.9%
    SAEs Leading to Discontinuation
    70
    7.3%
    AEs
    1123
    117.1%
    Related AEs
    737
    76.9%
    AEs Leading to Discontinuation
    103
    10.7%
    8. Primary Outcome
    Title OL; Number of Participants With AEs of Special Interest
    Description 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).
    Time Frame Day 365 to Day 1821

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants, all participants who received at least 1 dose of study medication
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1184
    Infections/Infestations
    957
    99.8%
    Total Neoplasms
    168
    17.5%
    Malignant Neoplasms
    56
    5.8%
    Benign and Unspecified Neoplasms
    112
    11.7%
    Pre-specified Autoimmune Disorders
    67
    7%
    Pre-specified Acute Infusional AEs
    82
    8.6%
    Pre-specified Peri-Infusional AEs
    219
    22.8%
    9. Primary Outcome
    Title OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
    Description 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.
    Time Frame Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Population.
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1184
    Low HGB (LLN=1.5%)
    70
    7.3%
    Low hematocrit (LLN=36%)
    53
    5.5%
    Erythrocytes (LLN=3.72-4.27 x10*6 c/uL)
    25
    2.6%
    Low PLT (LLN=140-157*10^9 c/L)
    23
    2.4%
    High PLT (ULN=415-440*10^9 c/L)
    10
    1%
    Low leukocytes (LLN= 4-9*10^3 c/uL)
    110
    11.5%
    High leukocytes (ULN = 10.5-30*10^3 c/uL)
    162
    16.9%
    Low neutrophils + bands (LLN= 1.5-2.9*10^3 c/uL)
    31
    3.2%
    Low lymphocytes (LLN= 0.7-2.9*10^3 c/uL)
    220
    22.9%
    High lymphocytes (ULN= 4.5-13.3*10^3 c/uL)
    5
    0.5%
    High monocytes (ULN=1-3.9*10^3 c/uL)
    11
    1.1%
    High basophils (ULN= 0.6*10^3 c/uL)
    4
    0.4%
    High eosinophils (ULN= 1.5*10^3 c/uL)
    151
    15.7%
    10. Primary Outcome
    Title OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria
    Description 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
    Time Frame Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Population. One participant was not evaluated for liver function abnormalities.
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1183
    High ALP (ULN=150 U/L)
    12
    1.3%
    High AST (ULN=80 U/L)
    38
    4%
    High ALT (ULN=34-47 U/L)
    54
    5.6%
    High GGT (ULN=43-54 U/L)
    91
    9.5%
    High bilirubin (ULN=0.3 mg/dL)
    9
    0.9%
    High BUN (normal=4-25 mg/dL)
    108
    11.3%
    High creatinine (ULN=14.6 pg/mg)
    204
    21.3%
    11. Primary Outcome
    Title OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria
    Description 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
    Time Frame Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Population. One participant was not evaluated for electrolyte abnormalities.
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1183
    Low Na (LLN=135 mEq/L)
    16
    1.7%
    High Na (ULN=148 mEq/L)
    1
    0.1%
    Low K (LLN=3.5 mEq/L)
    77
    8%
    High K (ULN=5.5 mEq/L)
    72
    7.5%
    Low Cl (LLN= 96 mEq/L)
    5
    0.5%
    High Cl (ULN=109 mEq/L)
    2
    0.2%
    Low Ca (LLN=8.5 mg/dL)
    2
    0.2%
    High Ca (ULN=11 mg/dL)
    0
    0%
    Low P (LLN=2.5 mg/dL)
    17
    1.8%
    High P (ULN 7.1 mg/dL)
    27
    2.8%
    12. Primary Outcome
    Title OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria
    Description 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
    Time Frame Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication

    Outcome Measure Data

    Analysis Population Description
    All Treated Population. N=Number of Participants Analyzed, n=number of participants with measurements at time point
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1184
    Low Glu, n=1184
    207
    21.6%
    High Glu, n=1184
    61
    6.4%
    Low fasting Glu, n=647 (LLN=65 mg/dL)
    647
    67.5%
    High fasting Glu, n=647 (ULN=115 mg/dL)
    41
    4.3%
    Low protein, n=1183 (LLN=6 g/dL)
    12
    1.3%
    High protein, n=1183 (ULN=8.5 g/dL)
    2
    0.2%
    Low albumin, n=1183 (LLN=3.5 g/dL)
    40
    4.2%
    High uric acid, n=1183 (ULN=8.7 mg/dL)
    19
    2%
    High urine protein, n=1184 (normal=trace)
    125
    13%
    High urine glucose, n=1184 (normal=negative)
    51
    5.3%
    High urine ketones, n=33 (normal=negative)
    0
    0%
    High urine blood, n=1184 (normal=negative)
    310
    32.3%
    High leukocyte esterase, n=32
    12
    1.3%
    High urine WBC, n=852
    429
    44.7%
    High urine RBC, n=852
    403
    42%
    13. Primary Outcome
    Title OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities
    Description 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.
    Time Frame Days 365 to Day 1821

    Outcome Measure Data

    Analysis Population Description
    All Treated Population.
    Arm/Group Title OL ABA
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1184
    Number [participants]
    0
    0%
    14. Secondary Outcome
    Title DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
    Description 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.
    Time Frame Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title All Treated Participants
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.
    Measure Participants 1296
    Anti-abatacept antibodies (n=1228)
    66
    6.9%
    Anti-CTLA4 antibodies (n=1296)
    48
    5%
    Total antibodies (n=1296)
    107
    11.2%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Open Label (OL) Abatacept Abatacept (ABA) Placebo (PLA)
    Arm/Group Description Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period. 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. 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.
    All Cause Mortality
    Open Label (OL) Abatacept Abatacept (ABA) Placebo (PLA)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Open Label (OL) Abatacept Abatacept (ABA) Placebo (PLA)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 425/1184 (35.9%) 124/959 (12.9%) 59/482 (12.2%)
    Blood and lymphatic system disorders
    ANAEMIA 3/1184 (0.3%) 2/959 (0.2%) 2/482 (0.4%)
    PANCYTOPENIA 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    LYMPHADENITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LYMPHADENOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BONE MARROW FAILURE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    FEBRILE NEUTROPENIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BONE MARROW TOXICITY 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    Cardiac disorders
    ARRHYTHMIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BRADYCARDIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    TACHYCARDIA 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    PERICARDITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ATRIAL FLUTTER 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    CARDIAC ARREST 3/1184 (0.3%) 2/959 (0.2%) 1/482 (0.2%)
    CARDIOMYOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ANGINA PECTORIS 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    ANGINA UNSTABLE 5/1184 (0.4%) 0/959 (0%) 2/482 (0.4%)
    CARDIAC FAILURE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    CARDIAC TAMPONADE 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    CARDIOGENIC SHOCK 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ATRIAL FIBRILLATION 4/1184 (0.3%) 0/959 (0%) 1/482 (0.2%)
    SICK SINUS SYNDROME 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    AORTIC VALVE DISEASE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MYOCARDIAL ISCHAEMIA 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    PERICARDIAL EFFUSION 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    MITRAL VALVE STENOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MYOCARDIAL INFARCTION 14/1184 (1.2%) 0/959 (0%) 1/482 (0.2%)
    ACUTE CORONARY SYNDROME 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    CORONARY ARTERY DISEASE 6/1184 (0.5%) 0/959 (0%) 0/482 (0%)
    CORONARY ARTERY STENOSIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    HEART VALVE INCOMPETENCE 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    ISCHAEMIC CARDIOMYOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CONGESTIVE CARDIOMYOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CORONARY ARTERY OCCLUSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MITRAL VALVE INCOMPETENCE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CARDIAC FAILURE CONGESTIVE 7/1184 (0.6%) 2/959 (0.2%) 2/482 (0.4%)
    HYPERTENSIVE HEART DISEASE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ACUTE MYOCARDIAL INFARCTION 7/1184 (0.6%) 0/959 (0%) 1/482 (0.2%)
    ATRIOVENTRICULAR BLOCK COMPLETE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ARTERIOSCLEROSIS CORONARY ARTERY 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    Congenital, familial and genetic disorders
    CONGENITAL CEREBRAL CYST 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Ear and labyrinth disorders
    SUDDEN HEARING LOSS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DEAFNESS NEUROSENSORY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NEUROSENSORY HYPOACUSIS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    Endocrine disorders
    HYPERTHYROIDISM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Eye disorders
    CATARACT 1/1184 (0.1%) 1/959 (0.1%) 2/482 (0.4%)
    PTERYGIUM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SCLEROMALACIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    Gastrointestinal disorders
    NAUSEA 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    COLITIS 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    VOMITING 2/1184 (0.2%) 2/959 (0.2%) 0/482 (0%)
    DIARRHOEA 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    DYSPEPSIA 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    FAECALOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GASTRITIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    GINGIVITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ANAL FISSURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CONSTIPATION 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    DIVERTICULUM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HAEMORRHOIDS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    OESOPHAGITIS 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    PANCREATITIS 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    COLONIC ATONY 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    GASTRIC ULCER 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    ABDOMINAL PAIN 7/1184 (0.6%) 2/959 (0.2%) 0/482 (0%)
    INGUINAL HERNIA 5/1184 (0.4%) 0/959 (0%) 0/482 (0%)
    ABDOMINAL HERNIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    UMBILICAL HERNIA 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    COLITIS ISCHAEMIC 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GASTRITIS EROSIVE 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    OESOPHAGEAL SPASM 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    OESOPHAGEAL ULCER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PANCREATITIS ACUTE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ABDOMINAL DISTENSION 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ABDOMINAL PAIN UPPER 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    INTESTINAL ISCHAEMIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    INTESTINAL OBSTRUCTION 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    DIVERTICULAR PERFORATION 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    IRRITABLE BOWEL SYNDROME 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MESENTERIC ARTERY EMBOLISM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LARGE INTESTINE PERFORATION 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ABDOMINAL HERNIA OBSTRUCTIVE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GASTROINTESTINAL HAEMORRHAGE 2/1184 (0.2%) 0/959 (0%) 3/482 (0.6%)
    SMALL INTESTINAL OBSTRUCTION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    LOWER GASTROINTESTINAL HAEMORRHAGE 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    UPPER GASTROINTESTINAL HAEMORRHAGE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    General disorders
    DEATH 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    HERNIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    FATIGUE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MALAISE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PYREXIA 4/1184 (0.3%) 1/959 (0.1%) 1/482 (0.2%)
    ASTHENIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CHEST PAIN 13/1184 (1.1%) 4/959 (0.4%) 3/482 (0.6%)
    HYPERTHERMIA 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    IMPAIRED HEALING 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HERNIA OBSTRUCTIVE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Hepatobiliary disorders
    HEPATITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CHOLANGITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HEPATIC MASS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LIVER INJURY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BILIARY COLIC 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CHOLECYSTITIS 9/1184 (0.8%) 0/959 (0%) 0/482 (0%)
    CHOLELITHIASIS 10/1184 (0.8%) 3/959 (0.3%) 3/482 (0.6%)
    CHOLECYSTITIS ACUTE 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    Immune system disorders
    ANAPHYLACTIC REACTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Infections and infestations
    SEPSIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    ABSCESS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    EMPYEMA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    INFLUENZA 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    PNEUMONIA 12/1184 (1%) 4/959 (0.4%) 3/482 (0.6%)
    SINUSITIS 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    UROSEPSIS 3/1184 (0.3%) 1/959 (0.1%) 0/482 (0%)
    BRONCHITIS 10/1184 (0.8%) 3/959 (0.3%) 0/482 (0%)
    CELLULITIS 6/1184 (0.5%) 1/959 (0.1%) 1/482 (0.2%)
    CERVICITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ERYSIPELAS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BACTERAEMIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    CANDIDIASIS 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    HEPATITIS E 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ABSCESS LIMB 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    APPENDICITIS 5/1184 (0.4%) 0/959 (0%) 0/482 (0%)
    BONE ABSCESS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    EPIGLOTTITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    OTITIS MEDIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SEPTIC SHOCK 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    ASPERGILLOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HERPES ZOSTER 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    OSTEOMYELITIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    TOOTH ABSCESS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    BRONCHIECTASIS 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    DIVERTICULITIS 6/1184 (0.5%) 0/959 (0%) 0/482 (0%)
    HERPES SIMPLEX 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG INFECTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PYELONEPHRITIS 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    GASTROENTERITIS 6/1184 (0.5%) 0/959 (0%) 0/482 (0%)
    LOBAR PNEUMONIA 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    VIRAL INFECTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    WOUND INFECTION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    BRONCHOPNEUMONIA 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    SYSTEMIC MYCOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BONE TUBERCULOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CANDIDA PNEUMONIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CHRONIC SINUSITIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    BURSITIS INFECTIVE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ESCHERICHIA SEPSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HUMAN EHRLICHIOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PERIRECTAL ABSCESS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ARTHRITIS BACTERIAL 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BACTERIAL INFECTION 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    HAEMATOMA INFECTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    INFECTED SKIN ULCER 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    LOCALISED INFECTION 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    DIARRHOEA INFECTIOUS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PYELONEPHRITIS ACUTE 6/1184 (0.5%) 2/959 (0.2%) 0/482 (0%)
    SUBCUTANEOUS ABSCESS 1/1184 (0.1%) 2/959 (0.2%) 0/482 (0%)
    OSTEOMYELITIS CHRONIC 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PERITONSILLAR ABSCESS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PNEUMONIA HAEMOPHILUS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    STAPHYLOCOCCAL SEPSIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    PNEUMONIA PNEUMOCOCCAL 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RESPIRATORY MONILIASIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LYMPH NODE TUBERCULOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PNEUMONIA STREPTOCOCCAL 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    URINARY TRACT INFECTION 6/1184 (0.5%) 2/959 (0.2%) 1/482 (0.2%)
    DEVICE RELATED INFECTION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    INCISION SITE CELLULITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CELLULITIS STAPHYLOCOCCAL 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    POST PROCEDURAL INFECTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    STREPTOCOCCAL BACTERAEMIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GASTROENTERITIS SALMONELLA 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    GASTROINTESTINAL INFECTION 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    STAPHYLOCOCCAL BACTERAEMIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PELVIC INFLAMMATORY DISEASE 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    STAPHYLOCOCCAL OSTEOMYELITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CLOSTRIDIUM DIFFICILE COLITIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    POSTOPERATIVE WOUND INFECTION 5/1184 (0.4%) 0/959 (0%) 0/482 (0%)
    BRONCHOPULMONARY ASPERGILLOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PNEUMOCYSTIS JIROVECI PNEUMONIA 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    LOWER RESPIRATORY TRACT INFECTION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Injury, poisoning and procedural complications
    FALL 4/1184 (0.3%) 2/959 (0.2%) 0/482 (0%)
    OVERDOSE 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    POISONING 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    UNDERDOSE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LIMB INJURY 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    HIP FRACTURE 8/1184 (0.7%) 0/959 (0%) 0/482 (0%)
    RIB FRACTURE 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    FOOT FRACTURE 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    ANKLE FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DEVICE FAILURE 3/1184 (0.3%) 1/959 (0.1%) 0/482 (0%)
    TENDON RUPTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    WRIST FRACTURE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    FIBULA FRACTURE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    PELVIC FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PROCEDURAL PAIN 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SKIN LACERATION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    STRESS FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    FOREARM FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HUMERUS FRACTURE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    MEDICATION ERROR 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    WOUND DEHISCENCE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    CLAVICLE FRACTURE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    JOINT DISLOCATION 2/1184 (0.2%) 1/959 (0.1%) 1/482 (0.2%)
    BURNS THIRD DEGREE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    DEVICE DISLOCATION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LOWER LIMB FRACTURE 3/1184 (0.3%) 1/959 (0.1%) 0/482 (0%)
    PUBIC RAMI FRACTURE 1/1184 (0.1%) 2/959 (0.2%) 0/482 (0%)
    UPPER LIMB FRACTURE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    LIMB CRUSHING INJURY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    FACIAL BONES FRACTURE 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    FEMORAL NECK FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    TRAUMATIC LIVER INJURY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DISLOCATION OF VERTEBRA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DRUG ADMINISTRATION ERROR 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUMBAR VERTEBRAL FRACTURE 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    THERAPEUTIC AGENT TOXICITY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    INCORRECT DOSE ADMINISTERED 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    MEDICAL DEVICE COMPLICATION 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    SPINAL COMPRESSION FRACTURE 2/1184 (0.2%) 2/959 (0.2%) 0/482 (0%)
    SUTURE RELATED COMPLICATION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    POST PROCEDURAL COMPLICATION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    DISLOCATION OF JOINT PROSTHESIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    Investigations
    HIV TEST POSITIVE 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    HAEMATOCRIT DECREASED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BLOOD GLUCOSE INCREASED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    TRANSAMINASES INCREASED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ELECTROCARDIOGRAM CHANGE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HEPATIC ENZYME INCREASED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ELECTROCARDIOGRAM ST-T SEGMENT ABNORMAL 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Metabolism and nutrition disorders
    OBESITY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DEHYDRATION 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    HYPONATRAEMIA 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    HYPERGLYCAEMIA 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    DIABETES MELLITUS 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    DIABETES MELLITUS INADEQUATE CONTROL 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    Musculoskeletal and connective tissue disorders
    BURSITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ARTHRITIS 10/1184 (0.8%) 1/959 (0.1%) 1/482 (0.2%)
    BACK PAIN 5/1184 (0.4%) 0/959 (0%) 1/482 (0.2%)
    NECK PAIN 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    SYNOVITIS 4/1184 (0.3%) 0/959 (0%) 1/482 (0.2%)
    ARTHRALGIA 5/1184 (0.4%) 1/959 (0.1%) 2/482 (0.4%)
    FLANK PAIN 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ARTHROPATHY 1/1184 (0.1%) 1/959 (0.1%) 3/482 (0.6%)
    BONE EROSION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    OSTEOPOROSIS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    OSTEONECROSIS 4/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    FOOT DEFORMITY 8/1184 (0.7%) 0/959 (0%) 0/482 (0%)
    HAND DEFORMITY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    OSTEOARTHRITIS 27/1184 (2.3%) 3/959 (0.3%) 2/482 (0.4%)
    COSTOCHONDRITIS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    JOINT ANKYLOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    FINGER DEFORMITY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    JOINT DESTRUCTION 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    PAIN IN EXTREMITY 2/1184 (0.2%) 0/959 (0%) 1/482 (0.2%)
    RHEUMATOID NODULE 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    MUSCULOSKELETAL PAIN 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    RHEUMATOID ARTHRITIS 56/1184 (4.7%) 21/959 (2.2%) 9/482 (1.9%)
    OSTEOPOROTIC FRACTURE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ROTATOR CUFF SYNDROME 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    SPINAL OSTEOARTHRITIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    LUMBAR SPINAL STENOSIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    MUSCULOSKELETAL CHEST PAIN 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MUSCULOSKELETAL DISCOMFORT 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    INTERVERTEBRAL DISC DISORDER 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    SYSTEMIC LUPUS ERYTHEMATOSUS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    INTERVERTEBRAL DISC PROTRUSION 7/1184 (0.6%) 2/959 (0.2%) 0/482 (0%)
    INTERVERTEBRAL DISC DEGENERATION 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    LIPOMA 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    OSTEOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LEIOMYOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BREAST CANCER 6/1184 (0.5%) 1/959 (0.1%) 2/482 (0.4%)
    COLON ADENOMA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    LUNG NEOPLASM 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    ADENOMA BENIGN 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GASTRIC CANCER 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    LEIOMYOSARCOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    THYROID CANCER 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    BOWEN'S DISEASE 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    PROSTATE CANCER 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    KAPOSI'S SARCOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    UTERINE LEIOMYOMA 2/1184 (0.2%) 2/959 (0.2%) 0/482 (0%)
    ENDOMETRIAL CANCER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MALIGNANT MELANOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG ADENOCARCINOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SEBACEOUS CARCINOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BASAL CELL CARCINOMA 15/1184 (1.3%) 5/959 (0.5%) 3/482 (0.6%)
    PANCREATIC CARCINOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RENAL CELL CARCINOMA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    BREAST CANCER IN SITU 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG CANCER METASTATIC 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NON-HODGKIN'S LYMPHOMA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG NEOPLASM MALIGNANT 0/1184 (0%) 2/959 (0.2%) 0/482 (0%)
    PITUITARY TUMOUR BENIGN 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SQUAMOUS CELL CARCINOMA 7/1184 (0.6%) 1/959 (0.1%) 0/482 (0%)
    MYELODYSPLASTIC SYNDROME 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    CERVIX CARCINOMA STAGE II 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MALIGNANT MELANOMA IN SITU 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NON-SMALL CELL LUNG CANCER 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    SQUAMOUS CELL CARCINOMA OF SKIN 9/1184 (0.8%) 2/959 (0.2%) 0/482 (0%)
    SQUAMOUS CELL CARCINOMA OF THE CERVIX 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    SMALL CELL LUNG CANCER STAGE UNSPECIFIED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT TYPE) 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Nervous system disorders
    SYNCOPE 4/1184 (0.3%) 2/959 (0.2%) 0/482 (0%)
    HEADACHE 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    MIGRAINE 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    SCIATICA 5/1184 (0.4%) 0/959 (0%) 0/482 (0%)
    NEURALGIA 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    PRESYNCOPE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PARAESTHESIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HYPOAESTHESIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    RADICULOPATHY 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    ENCEPHALOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    POLYNEUROPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ISCHAEMIC STROKE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MOYAMOYA DISEASE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NERVE COMPRESSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CEREBRAL ISCHAEMIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CERVICAL MYELOPATHY 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SPINAL CLAUDICATION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CEREBRAL HAEMORRHAGE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LOSS OF CONSCIOUSNESS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NEUROPATHY PERIPHERAL 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CARPAL TUNNEL SYNDROME 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    NERVE ROOT COMPRESSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CAROTID ARTERY STENOSIS 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    CEREBROVASCULAR ACCIDENT 3/1184 (0.3%) 1/959 (0.1%) 1/482 (0.2%)
    CEREBROVASCULAR DISORDER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SUBARACHNOID HAEMORRHAGE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RUPTURED CEREBRAL ANEURYSM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    TRANSIENT ISCHAEMIC ATTACK 4/1184 (0.3%) 2/959 (0.2%) 1/482 (0.2%)
    COMPLEX REGIONAL PAIN SYNDROME 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    Psychiatric disorders
    ANXIETY 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    DEPRESSION 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    SUICIDE ATTEMPT 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    BIPOLAR DISORDER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MAJOR DEPRESSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MENTAL STATUS CHANGES 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Renal and urinary disorders
    RENAL INFARCT 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    NEPHROLITHIASIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CALCULUS URETERIC 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    RENAL AMYLOIDOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GLOMERULONEPHRITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RENAL FAILURE ACUTE 5/1184 (0.4%) 0/959 (0%) 1/482 (0.2%)
    URINARY INCONTINENCE 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    STRESS URINARY INCONTINENCE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Reproductive system and breast disorders
    CYSTOCELE 3/1184 (0.3%) 0/959 (0%) 0/482 (0%)
    ADENOMYOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    METRORRHAGIA 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    OVARIAN CYST 1/1184 (0.1%) 1/959 (0.1%) 0/482 (0%)
    ENDOMETRIOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    GYNAECOMASTIA 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    CERVICAL POLYP 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BREAST DISORDER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    MENOMETRORRHAGIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    UTERINE PROLAPSE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    UTERINE HAEMORRHAGE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    VAGINAL HAEMORRHAGE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    FIBROCYSTIC BREAST DISEASE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    BENIGN PROSTATIC HYPERPLASIA 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Respiratory, thoracic and mediastinal disorders
    ASTHMA 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    DYSPNOEA 1/1184 (0.1%) 1/959 (0.1%) 1/482 (0.2%)
    HAEMOPTYSIS 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    BRONCHOSPASM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    LUNG DISORDER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PLEURITIC PAIN 2/1184 (0.2%) 0/959 (0%) 1/482 (0.2%)
    BRONCHIAL POLYP 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    RHEUMATOID LUNG 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PLEURAL EFFUSION 2/1184 (0.2%) 2/959 (0.2%) 1/482 (0.2%)
    TRACHEAL STENOSIS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    BRONCHITIS CHRONIC 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    PULMONARY EMBOLISM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PULMONARY FIBROSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    STATUS ASTHMATICUS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RESPIRATORY FAILURE 4/1184 (0.3%) 1/959 (0.1%) 0/482 (0%)
    SLEEP APNOEA SYNDROME 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    NASAL SEPTUM DEVIATION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 2/1184 (0.2%) 3/959 (0.3%) 0/482 (0%)
    Skin and subcutaneous tissue disorders
    SKIN ULCER 1/1184 (0.1%) 0/959 (0%) 1/482 (0.2%)
    PANNICULITIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    SKIN FISSURES 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    DECUBITUS ULCER 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    LICHENOID KERATOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PYODERMA GANGRENOSUM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    DERMATITIS PSORIASIFORM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Social circumstances
    VICTIM OF HOMICIDE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Vascular disorders
    HYPOTENSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HYPERTENSION 4/1184 (0.3%) 1/959 (0.1%) 2/482 (0.4%)
    AORTIC ANEURYSM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    AORTIC STENOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    ARTERIOSCLEROSIS 2/1184 (0.2%) 1/959 (0.1%) 0/482 (0%)
    AORTIC DISSECTION 0/1184 (0%) 0/959 (0%) 1/482 (0.2%)
    ARTERIAL STENOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    VENOUS THROMBOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    EXTREMITY NECROSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    VASCULAR OCCLUSION 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    HYPERTENSIVE CRISIS 2/1184 (0.2%) 0/959 (0%) 0/482 (0%)
    DEEP VEIN THROMBOSIS 4/1184 (0.3%) 3/959 (0.3%) 1/482 (0.2%)
    ILIAC ARTERY EMBOLISM 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    RHEUMATOID VASCULITIS 0/1184 (0%) 1/959 (0.1%) 0/482 (0%)
    VENOUS THROMBOSIS LIMB 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    AXILLARY VEIN THROMBOSIS 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PERIPHERAL VASCULAR DISORDER 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    THROMBOPHLEBITIS SUPERFICIAL 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    PERIPHERAL ARTERIAL OCCLUSIVE DISEASE 1/1184 (0.1%) 0/959 (0%) 0/482 (0%)
    Other (Not Including Serious) Adverse Events
    Open Label (OL) Abatacept Abatacept (ABA) Placebo (PLA)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1010/1184 (85.3%) 715/959 (74.6%) 346/482 (71.8%)
    Blood and lymphatic system disorders
    ANAEMIA 65/1184 (5.5%) 18/959 (1.9%) 14/482 (2.9%)
    Eye disorders
    CONJUNCTIVITIS 72/1184 (6.1%) 22/959 (2.3%) 11/482 (2.3%)
    Gastrointestinal disorders
    NAUSEA 154/1184 (13%) 121/959 (12.6%) 56/482 (11.6%)
    VOMITING 101/1184 (8.5%) 58/959 (6%) 27/482 (5.6%)
    DIARRHOEA 186/1184 (15.7%) 96/959 (10%) 58/482 (12%)
    DYSPEPSIA 112/1184 (9.5%) 72/959 (7.5%) 24/482 (5%)
    ABDOMINAL PAIN 96/1184 (8.1%) 35/959 (3.6%) 16/482 (3.3%)
    ABDOMINAL PAIN UPPER 101/1184 (8.5%) 44/959 (4.6%) 18/482 (3.7%)
    General disorders
    FATIGUE 63/1184 (5.3%) 65/959 (6.8%) 25/482 (5.2%)
    PYREXIA 65/1184 (5.5%) 37/959 (3.9%) 18/482 (3.7%)
    CHEST PAIN 73/1184 (6.2%) 26/959 (2.7%) 11/482 (2.3%)
    OEDEMA PERIPHERAL 83/1184 (7%) 35/959 (3.6%) 31/482 (6.4%)
    Infections and infestations
    RHINITIS 67/1184 (5.7%) 28/959 (2.9%) 7/482 (1.5%)
    INFLUENZA 145/1184 (12.2%) 60/959 (6.3%) 30/482 (6.2%)
    SINUSITIS 198/1184 (16.7%) 66/959 (6.9%) 35/482 (7.3%)
    BRONCHITIS 229/1184 (19.3%) 52/959 (5.4%) 25/482 (5.2%)
    PHARYNGITIS 90/1184 (7.6%) 22/959 (2.3%) 12/482 (2.5%)
    GASTROENTERITIS 87/1184 (7.3%) 14/959 (1.5%) 7/482 (1.5%)
    NASOPHARYNGITIS 266/1184 (22.5%) 98/959 (10.2%) 46/482 (9.5%)
    URINARY TRACT INFECTION 195/1184 (16.5%) 78/959 (8.1%) 23/482 (4.8%)
    UPPER RESPIRATORY TRACT INFECTION 362/1184 (30.6%) 143/959 (14.9%) 74/482 (15.4%)
    Musculoskeletal and connective tissue disorders
    MYALGIA 69/1184 (5.8%) 33/959 (3.4%) 19/482 (3.9%)
    BACK PAIN 210/1184 (17.7%) 68/959 (7.1%) 28/482 (5.8%)
    MUSCLE SPASMS 70/1184 (5.9%) 21/959 (2.2%) 13/482 (2.7%)
    Nervous system disorders
    HEADACHE 216/1184 (18.2%) 195/959 (20.3%) 69/482 (14.3%)
    DIZZINESS 135/1184 (11.4%) 105/959 (10.9%) 43/482 (8.9%)
    Psychiatric disorders
    INSOMNIA 96/1184 (8.1%) 43/959 (4.5%) 14/482 (2.9%)
    DEPRESSION 76/1184 (6.4%) 37/959 (3.9%) 13/482 (2.7%)
    Respiratory, thoracic and mediastinal disorders
    COUGH 195/1184 (16.5%) 84/959 (8.8%) 37/482 (7.7%)
    RHINITIS ALLERGIC 77/1184 (6.5%) 18/959 (1.9%) 5/482 (1%)
    OROPHARYNGEAL PAIN 80/1184 (6.8%) 30/959 (3.1%) 25/482 (5.2%)
    Skin and subcutaneous tissue disorders
    RASH 85/1184 (7.2%) 45/959 (4.7%) 19/482 (3.9%)
    Vascular disorders
    HYPERTENSION 162/1184 (13.7%) 68/959 (7.1%) 24/482 (5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title BMS Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00048932
    Other Study ID Numbers:
    • IM101-031
    First Posted:
    Nov 13, 2002
    Last Update Posted:
    Nov 24, 2011
    Last Verified:
    Nov 1, 2011