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Open-Label, Multicenter Extension Study for Patients Completing Treatment Phase of a Rigel-Sponsored R935788 Studies

Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT00805467
Collaborator
(none)
624
Enrollment
76
Locations
4
Arms
60
Duration (Months)
8.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this new research study is to gain additional information about how safe and effective R935788 is over a longer period of time.

Condition or Disease Intervention/Treatment Phase
  • Drug: Fostamatinib Disodium (R935788)
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
624 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Multicenter Extension Study to Evaluate the Safety of R935788 in Patients With Rheumatoid Arthritis Who Have Completed the Treatment Phase of a Rigel-Sponsored R935788 Study
Study Start Date :
Aug 1, 2008
Actual Primary Completion Date :
Aug 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

R935788 50 mg tablet, orally, twice-a-day

Drug: Fostamatinib Disodium (R935788)
50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD
Other Names:
  • R935788

    		•
    Experimental: 2

    R935788 100 mg tablet, orally, twice-a-day

    Drug: Fostamatinib Disodium (R935788)
    50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD
    Other Names:
  • R935788

    		•
    Experimental: 3

    R935788 100 mg tablet, orally, once-a-day

    Drug: Fostamatinib Disodium (R935788)
    50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD
    Other Names:
  • R935788

    		•
    Experimental: 4

    R935788 150 mg tablet, orally, once-a-day

    Drug: Fostamatinib Disodium (R935788)
    50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD
    Other Names:
  • R935788

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Patients Who Had at Least 1 Treatment Emergent Adverse Event in Any Category [Entry in extension to end of study, up to a maximum of 5 years. (Variable by subject - median duration of 3 years)]

      AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event

    Secondary Outcome Measures

    1. DAS28-CRP Score [3 years]

      The Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS on a scale from 1 to 10, where scores greater than 5.1 are considered to indicate active disease, scores less than 3.2 are considered to indicate with well controlled disease, and scores less than 2.6 are considered to indicate remission. bid = twice daily, CRP = C-reactive protein, DAS28 = Disease Activity Score based on a 28 joint count, n/a = not applicable, qd = once daily

    2. HAQ-DI Score [3 years]

      Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygeine, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. A HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

    Eligibility Criteria

    Criteria

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

    • Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study

    • Patients who are being treated in Study C-788-006X

    • Patients who completed Studies C-788-010 or C-788-011 and did not withdraw due to adverse events

    • Patients who withdrew from Study C-788-010 at Month 4 or Month 5 because of a pre-defined lack of efficacy

    • Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative pregnancy test at the time of entry and at each laboratory determination.

    Exclusion Criteria:
    • The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:

    1. unresolved Grade 2 or greater toxicity in a RA protocol studying R788

    2. uncontrolled or poorly controlled hypertension;

    3. recent (within past 2 months) serious surgery or infectious disease;

    4. recent history (since enrollment in prior R788 study) of, or treatment for, a malignancy other than non-melanomatous skin cancer, or any history of lymphoma;

    5. known to be positive for Hepatitis B, Hepatitis C, HIV or Tuberculosis;

    6. interstitial pneumonitis or active pulmonary infection;

    7. known laboratory abnormalities: ALT > 1.2 x ULN, creatinine >1.5x ULN, an ANC <2,500/mm3 or 2.5 x 109/L, lymphocyte count < 600/mm3 or 0.6 x 109L, Hgb < 9 g/dL or 5 mmol/L, platelet count <125,000/mm3 or 125 x 109/L are excluded.

    • The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer = 12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine = 3 oz or 89 mL; 80 proof distilled spirits = 1.5 oz or 44 mL.

    • The patient is unable to report for clinical and laboratory monitoring as per protocol.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site La Jolla California United States
    2 Research Site Palm Desert California United States
    3 Research Site Palo Alto California United States
    4 Research Site San Diego California United States
    5 Research Site Santa Maria California United States
    6 Research Site Hamden Connecticut United States
    7 Research Site Washington District of Columbia United States
    8 Research Site Aventura Florida United States
    9 Research Site Boca Raton Florida United States
    10 Research Site Gainesville Florida United States
    11 Research Site Ocala Florida United States
    12 Research Site Orange Park Florida United States
    13 Research Site Orlando Florida United States
    14 Research Site South Miami Florida United States
    15 Research Site Venice Florida United States
    16 Research Site Boise Idaho United States
    17 Research Site Coeur D'Alene Idaho United States
    18 Research Site South Bend Indiana United States
    19 Research Site Elizabethtown Kentucky United States
    20 Research Site Cumberland Maryland United States
    21 Research Site Hagerstown Maryland United States
    22 Research Site Lansing Michigan United States
    23 Research Site Omaha Nebraska United States
    24 Research Site Roslyn New York United States
    25 Research Site Smithtown New York United States
    26 Research Site Raleigh North Carolina United States
    27 Research Site Mayfiled Village Ohio United States
    28 Research Site Erie Pennsylvania United States
    29 Research Site Willow Grove Pennsylvania United States
    30 Research Site Wyomissing Pennsylvania United States
    31 Research Site Jackson Tennessee United States
    32 Research Site Austin Texas United States
    33 Research Site San Antonio Texas United States
    34 Research Site Oklahoma City Washington United States
    35 Research Site Spokane Washington United States
    36 Research Site Antwerp Belgium
    37 Research Site Gent Belgium
    38 Research Site Liege Belgium
    39 Research Site Plovdiv Bulgaria
    40 Research Site Ruse Bulgaria
    41 Research Site Sofia Bulgaria
    42 Research Site Barranquilla Colombia
    43 Research Site Bogota Colombia
    44 Research Site Bucaramanga Colombia
    45 Research Site Medellín Colombia
    46 Research Site Bordeaux France
    47 Research Site Hamburg Germany
    48 Research Site Leipzig Germany
    49 Research Site Würzburg Germany
    50 Research Site Siena Italy
    51 Research Site Udine Italy
    52 Research Site Chihuahua Mexico
    53 Research Site Cuernava Mexico
    54 Research Site Del. Cuauhtemoc Mexico
    55 Research Site Guadalajara Mexico
    56 Research Site Leon Mexico
    57 Research Site Mexcio Mexico
    58 Research Site Mexico Mexico
    59 Research Site Morelia Mexico
    60 Research Site San Luis Potosí Mexico
    61 Research Site Jesus Maria Peru
    62 Research Site Lima Peru
    63 Research Site Białystok Poland
    64 Research Site Bytom Poland
    65 Research Site Elblag Poland
    66 Research Site Grodzisk Mazowiecki Poland
    67 Research Site Krakow Poland
    68 Research Site Lublin Poland
    69 Research Site Toruń Poland
    70 Research Site Wroclaw Poland
    71 Research Site Zyrardów Poland
    72 Research Site Brailari Romania
    73 Research Site Bucuresti Romania
    74 Research Site Cluj-Napoca Romania
    75 Research Site Sf. Gheorghe Romania
    76 Research Site Sibiu Romania

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    • Study Director: Chris O'Brien, MD, PhD, AstraZeneca

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00805467
    Other Study ID Numbers:
    • C-935788-012
    • D4300C00021
    First Posted:
    Dec 9, 2008
    Last Update Posted:
    Jun 25, 2014
    Last Verified:
    May 1, 2014
    Keywords provided by AstraZeneca
    RA
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid

    Study Results

    Participant Flow

    Recruitment Details A total of 624 patients were enrolled: 1, 59, 183 & 381 were allocated to the 50mg twice daily (bid), 100 mg once daily (qd), 150 mg qd and 100 mg bid groups, respectively. As this was a long-term extension study no specific end date was given. Patients who were ongoing when the study was terminated are shown as completers.
    Pre-assignment Detail Treatments were assigned according to those given in the qualifying studies. All patients received investigational product.
    Arm/Group Title Fostamatinib 50 mg Bid Fostamatinib 100 mg qd Fostamatinib 150 mg qd Fostamatinib 100 mg Bid
    Arm/Group Description Oral treatment Oral treatment Oral treatment Oral treatment
    Period Title: Overall Study
    STARTED 1 59 183 381
    Enrolled But Did Not Receive Treatment 0 0 0 0
    COMPLETED 1 25 80 144
    NOT COMPLETED 0 34 103 237

    Baseline Characteristics

    Arm/Group Title Fostamatinib 50 mg Bid Fostamatinib 100 mg qd Fostamatinib 150 mg qd Fostamatinib 100 mg Bid Total
    Arm/Group Description Oral treatment Oral treatment Oral treatment Oral treatment Total of all reporting groups
    Overall Participants 1 59 183 381 624
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70
    (NA)
    51.4
    (11.15)
    51.7
    (13.32)
    53.8
    (12.36)
    53.0
    (12.58)
    Sex: Female, Male (Count of Participants)
    Female
    1
    100%
    53
    89.8%
    157
    85.8%
    324
    85%
    535
    85.7%
    Male
    0
    0%
    6
    10.2%
    26
    14.2%
    57
    15%
    89
    14.3%
    Race/Ethnicity, Customized (Number) [Number]
    Caucasian
    0
    0%
    18
    30.5%
    88
    48.1%
    184
    48.3%
    290
    46.5%
    Black
    1
    100%
    1
    1.7%
    6
    3.3%
    14
    3.7%
    22
    3.5%
    Hispanic
    0
    0%
    40
    67.8%
    88
    48.1%
    179
    47%
    307
    49.2%
    Asian
    0
    0%
    0
    0%
    0
    0%
    2
    0.5%
    2
    0.3%
    Other
    0
    0%
    0
    0%
    1
    0.5%
    2
    0.5%
    3
    0.5%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Patients Who Had at Least 1 Treatment Emergent Adverse Event in Any Category
    Description AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event
    Time Frame Entry in extension to end of study, up to a maximum of 5 years. (Variable by subject - median duration of 3 years)

    Outcome Measure Data

    Analysis Population Description
    The full analysis set includes those patients who received at least 1 dose of investigational product, and were summarised according to treatment first received in this study (intention-to-treat principle).
    Arm/Group Title Fostamatinib 50 mg Bid Fostamatinib 100 mg qd Fostamatinib 150 mg qd Fostamatinib 100 mg Bid
    Arm/Group Description Oral treatment Oral treatment Oral treatment Oral treatment
    Measure Participants 1 59 183 381
    Any AE
    100
    91.5
    90.7
    88.7
    Any fatal AE
    0
    1.7
    3.8
    1.6
    Any SAE (including fatal AEs)
    100
    3.4
    18.6
    20.2
    Any AE leading to termination of study therapy
    0
    22.0
    16.4
    15.2
    2. Secondary Outcome
    Title DAS28-CRP Score
    Description The Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS on a scale from 1 to 10, where scores greater than 5.1 are considered to indicate active disease, scores less than 3.2 are considered to indicate with well controlled disease, and scores less than 2.6 are considered to indicate remission. bid = twice daily, CRP = C-reactive protein, DAS28 = Disease Activity Score based on a 28 joint count, n/a = not applicable, qd = once daily
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    Number of participants are those with baseline data. Baseline defined at entry into qualifying study or at entry into this study if more than 14 days since last dose in qualifying study. As no imputation was applied, the numbers at subsequent visits are lower.
    Arm/Group Title Fostamatinib 50 mg Bid Fostamatinib 100 mg qd Fostamatinib 150 mg qd Fostamatinib 100 mg Bid
    Arm/Group Description Oral treatment Oral treatment Oral treatment Oral treatment
    Measure Participants 1 55 181 374
    Baseline (n=1, 55, 181, 374)
    5.27
    (NA)
    5.34
    (1.123)
    5.31
    (1.162)
    5.36
    (1.259)
    Quarter 4 (n=1, 41, 136, 254)
    2.00
    (NA)
    3.57
    (1.408)
    3.46
    (1.282)
    3.44
    (1.453)
    Quarter 8 (n=1, 33, 114, 201)
    2.92
    (NA)
    3.43
    (1.412)
    3.25
    (1.290)
    3.35
    (1.484)
    Quarter 12 (n=1, 30, 94, 174)
    2.31
    (NA)
    3.36
    (1.376)
    3.07
    (1.055)
    3.27
    (1.373)
    3. Secondary Outcome
    Title HAQ-DI Score
    Description Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygeine, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. A HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    Number of participants are those with baseline data. Baseline defined at entry into qualifying study or at entry into this study if more than 14 days since last dose in qualifying study. As no imputation was applied, the numbers at subsequent visits are lower.
    Arm/Group Title Fostamatinib 50 mg Bid Fostamatinib 100 mg qd Fostamatinib 150 mg qd Fostamatinib 100 mg Bid
    Arm/Group Description Oral treatment Oral treatment Oral treatment Oral treatment
    Measure Participants 1 56 181 376
    Baseline (n=1, 56, 181, 376)
    1.25
    (NA)
    1.50
    (0.735)
    1.46
    (0.707)
    1.46
    (0.715)
    Quarter 4 (n=1, 41, 138, 254)
    0.57
    (NA)
    1.00
    (0.677)
    1.07
    (0.726)
    0.99
    (0.722)
    Quarter 8 (n=1, 33, 107, 201)
    0.43
    (NA)
    1.00
    (0.657)
    1.02
    (0.720)
    0.95
    (0.703)
    Quarter 12 (n=1, 30, 94, 176)
    0.38
    (NA)
    1.01
    (0.651)
    0.98
    (0.718)
    0.96
    (0.687)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title 100 MG BID 100 MG QD 150 MG QD 50 MG BID
    Arm/Group Description
    All Cause Mortality
    100 MG BID 100 MG QD 150 MG QD 50 MG BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    100 MG BID 100 MG QD 150 MG QD 50 MG BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 77/381 (20.2%) 2/59 (3.4%) 34/183 (18.6%) 1/1 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    PANCYTOPENIA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    THROMBOTIC THROMBOCYTOPENIC PURPURA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Cardiac disorders
    ARTERIOSPASM CORONARY 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ATRIAL FIBRILLATION 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CARDIAC ARREST 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CARDIAC FAILURE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CARDIAC FAILURE CONGESTIVE 2/381 (0.5%) 3 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CARDIO-RESPIRATORY ARREST 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CARDIOPULMONARY FAILURE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CORONARY ARTERY DISEASE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    INTRACARDIAC THROMBUS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    MYOCARDIAL INFARCTION 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    VENTRICULAR DYSFUNCTION 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Endocrine disorders
    GOITRE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Eye disorders
    PANOPHTHALMITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL PAIN 3/381 (0.8%) 3 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    COLITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    COLITIS MICROSCOPIC 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    COLONIC POLYP 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    DIARRHOEA 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    DIVERTICULUM 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    FAECALOMA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    GASTRIC PERFORATION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    GASTRITIS 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    GASTROINTESTINAL PERFORATION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    HIATUS HERNIA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    ILEUS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PANCREATITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PANCREATITIS ACUTE 0/381 (0%) 0 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    PANCREATITIS HAEMORRHAGIC 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    RECTAL PROLAPSE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    SMALL INTESTINAL OBSTRUCTION 0/381 (0%) 0 0/59 (0%) 0 0/183 (0%) 0 1/1 (100%) 1
    UMBILICAL HERNIA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    VOMITING 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    General disorders
    CHEST PAIN 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    DEVICE DISLOCATION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PYREXIA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    SUDDEN DEATH 0/381 (0%) 0 1/59 (1.7%) 1 0/183 (0%) 0 0/1 (0%) 0
    Hepatobiliary disorders
    CHOLECYSTITIS 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CHOLECYSTITIS ACUTE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CHOLELITHIASIS 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    HEPATIC CIRRHOSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    HEPATIC STEATOSIS 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Infections and infestations
    ABSCESS SOFT TISSUE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    APPENDICITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    BRONCHITIS 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    BURSITIS INFECTIVE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CELLULITIS 4/381 (1%) 4 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CYTOMEGALOVIRUS HEPATITIS 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    CYTOMEGALOVIRUS INFECTION 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    DIVERTICULITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    DYSENTERY 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    EPIGLOTTITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ERYTHEMA MIGRANS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ESCHERICHIA SEPSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    GASTROENTERITIS 2/381 (0.5%) 2 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    GIARDIASIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    INFECTED BITES 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    LOBAR PNEUMONIA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    MENINGITIS BACTERIAL 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    NECROTISING FASCIITIS 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    OSTEOMYELITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PERITONITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PNEUMONIA 6/381 (1.6%) 7 0/59 (0%) 0 3/183 (1.6%) 3 0/1 (0%) 0
    PNEUMONIA STAPHYLOCOCCAL 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PYELONEPHRITIS 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    SEPSIS 1/381 (0.3%) 1 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    SEPTIC SHOCK 0/381 (0%) 0 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    SINUSITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 1/1 (100%) 1
    URINARY TRACT INFECTION 2/381 (0.5%) 2 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    UROSEPSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    VARICELLA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    VIRAL INFECTION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    WOUND INFECTION STAPHYLOCOCCAL 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Injury, poisoning and procedural complications
    DISLOCATION OF VERTEBRA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    JOINT DISLOCATION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    MUSCLE RUPTURE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PUBIS FRACTURE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    SUBDURAL HAEMATOMA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    SPINAL FRACTURE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Metabolism and nutrition disorders
    DEHYDRATION 3/381 (0.8%) 3 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    HYPOKALAEMIA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Musculoskeletal and connective tissue disorders
    CERVICAL SPINAL STENOSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    INTERVERTEBRAL DISC PROTRUSION 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    LUMBAR SPINAL STENOSIS 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    MUSCULOSKELETAL PAIN 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    MYOSITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    OSTEOARTHRITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    RHEUMATOID ARTHRITIS 2/381 (0.5%) 2 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    SPINAL OSTEOARTHRITIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ANAL CANCER 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    BASOSQUAMOUS CARCINOMA OF SKIN 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    BRAIN NEOPLASM MALIGNANT 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    BREAST CANCER 1/381 (0.3%) 1 0/59 (0%) 0 2/183 (1.1%) 2 0/1 (0%) 0
    CERVIX CARCINOMA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    COLON CANCER STAGE IV 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    DIFFUSE LARGE B-CELL LYMPHOMA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    LARGE INTESTINE CARCINOMA 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    LUNG SQUAMOUS CELL CARCINOMA STAGE UNSPECIFIED 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    PARATHYROID TUMOUR BENIGN 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    THYROID CANCER 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    UTERINE LEIOMYOMA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Nervous system disorders
    ACUTE POLYNEUROPATHY 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    CEREBRAL HAEMORRHAGE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    ISCHAEMIC STROKE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    LUMBAR RADICULOPATHY 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PRESYNCOPE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    RADICULOPATHY 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    SYNCOPE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ABORTION SPONTANEOUS INCOMPLETE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Psychiatric disorders
    ANXIETY 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Renal and urinary disorders
    RENAL FAILURE ACUTE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Reproductive system and breast disorders
    ENDOMETRIAL HYPERTROPHY 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    OVARIAN CYST 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    POSTMENOPAUSAL HAEMORRHAGE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    VAGINAL PROLAPSE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ASTHMA 0/381 (0%) 0 0/59 (0%) 0 0/183 (0%) 0 1/1 (100%) 1
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 3 0/1 (0%) 0
    DYSPNOEA 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    LUNG INFILTRATION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    PULMONARY EMBOLISM 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    PULMONARY FIBROSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Surgical and medical procedures
    HIP ARTHROPLASTY 1/381 (0.3%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    IMPLANTABLE DEFIBRILLATOR INSERTION 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    KNEE ARTHROPLASTY 0/381 (0%) 0 1/59 (1.7%) 1 0/183 (0%) 0 0/1 (0%) 0
    Vascular disorders
    AORTIC ANEURYSM 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    ARTERIOSCLEROSIS 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    DEEP VEIN THROMBOSIS 0/381 (0%) 0 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    HYPERTENSIVE CRISIS 1/381 (0.3%) 1 0/59 (0%) 0 1/183 (0.5%) 1 0/1 (0%) 0
    HYPOTENSION 1/381 (0.3%) 1 0/59 (0%) 0 0/183 (0%) 0 0/1 (0%) 0
    Other (Not Including Serious) Adverse Events
    100 MG BID 100 MG QD 150 MG QD 50 MG BID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 306/381 (80.3%) 49/59 (83.1%) 141/183 (77%) 1/1 (100%)
    Blood and lymphatic system disorders
    ANAEMIA 24/381 (6.3%) 28 1/59 (1.7%) 1 13/183 (7.1%) 17 0/1 (0%) 0
    NEUTROPENIA 30/381 (7.9%) 34 5/59 (8.5%) 5 10/183 (5.5%) 13 0/1 (0%) 0
    Eye disorders
    CONJUNCTIVITIS 11/381 (2.9%) 11 3/59 (5.1%) 3 5/183 (2.7%) 5 0/1 (0%) 0
    Gastrointestinal disorders
    ABDOMINAL PAIN 10/381 (2.6%) 10 3/59 (5.1%) 3 3/183 (1.6%) 4 0/1 (0%) 0
    DIARRHOEA 96/381 (25.2%) 151 20/59 (33.9%) 36 60/183 (32.8%) 93 0/1 (0%) 0
    DYSPEPSIA 8/381 (2.1%) 8 3/59 (5.1%) 4 3/183 (1.6%) 4 1/1 (100%) 1
    GASTRITIS 14/381 (3.7%) 15 5/59 (8.5%) 5 8/183 (4.4%) 8 0/1 (0%) 0
    HAEMORRHOIDS 1/381 (0.3%) 1 4/59 (6.8%) 4 0/183 (0%) 0 0/1 (0%) 0
    NAUSEA 27/381 (7.1%) 31 3/59 (5.1%) 4 11/183 (6%) 12 0/1 (0%) 0
    VOMITING 23/381 (6%) 27 5/59 (8.5%) 9 10/183 (5.5%) 11 0/1 (0%) 0
    General disorders
    CHEST PAIN 6/381 (1.6%) 6 3/59 (5.1%) 3 0/183 (0%) 0 0/1 (0%) 0
    OEDEMA PERIPHERAL 24/381 (6.3%) 34 3/59 (5.1%) 3 7/183 (3.8%) 8 0/1 (0%) 0
    Infections and infestations
    BRONCHITIS 26/381 (6.8%) 38 3/59 (5.1%) 4 14/183 (7.7%) 20 0/1 (0%) 0
    INFLUENZA 36/381 (9.4%) 54 8/59 (13.6%) 15 18/183 (9.8%) 20 0/1 (0%) 0
    NASOPHARYNGITIS 27/381 (7.1%) 31 3/59 (5.1%) 3 10/183 (5.5%) 12 0/1 (0%) 0
    PHARYNGITIS 16/381 (4.2%) 19 5/59 (8.5%) 6 5/183 (2.7%) 6 0/1 (0%) 0
    SINUSITIS 26/381 (6.8%) 37 3/59 (5.1%) 3 4/183 (2.2%) 4 0/1 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 51/381 (13.4%) 76 7/59 (11.9%) 8 20/183 (10.9%) 29 1/1 (100%) 1
    URINARY TRACT INFECTION 72/381 (18.9%) 125 12/59 (20.3%) 32 28/183 (15.3%) 45 0/1 (0%) 0
    Investigations
    BLOOD PRESSURE INCREASED 27/381 (7.1%) 35 1/59 (1.7%) 1 11/183 (6%) 11 0/1 (0%) 0
    NEUTROPHIL COUNT DECREASED 6/381 (1.6%) 10 0/59 (0%) 0 2/183 (1.1%) 5 1/1 (100%) 1
    TRANSAMINASES INCREASED 35/381 (9.2%) 45 7/59 (11.9%) 8 15/183 (8.2%) 16 0/1 (0%) 0
    Metabolism and nutrition disorders
    HYPERLIPIDAEMIA 3/381 (0.8%) 3 3/59 (5.1%) 3 1/183 (0.5%) 1 0/1 (0%) 0
    HYPOKALAEMIA 9/381 (2.4%) 16 3/59 (5.1%) 3 2/183 (1.1%) 2 0/1 (0%) 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 17/381 (4.5%) 25 1/59 (1.7%) 2 10/183 (5.5%) 16 0/1 (0%) 0
    BACK PAIN 30/381 (7.9%) 35 3/59 (5.1%) 3 9/183 (4.9%) 11 0/1 (0%) 0
    BURSITIS 16/381 (4.2%) 20 4/59 (6.8%) 5 5/183 (2.7%) 5 0/1 (0%) 0
    OSTEOARTHRITIS 10/381 (2.6%) 10 3/59 (5.1%) 3 2/183 (1.1%) 2 0/1 (0%) 0
    RHEUMATOID ARTHRITIS 38/381 (10%) 69 3/59 (5.1%) 6 10/183 (5.5%) 16 0/1 (0%) 0
    TENDONITIS 2/381 (0.5%) 3 4/59 (6.8%) 4 2/183 (1.1%) 2 0/1 (0%) 0
    Nervous system disorders
    HEADACHE 33/381 (8.7%) 49 4/59 (6.8%) 7 23/183 (12.6%) 35 0/1 (0%) 0
    Renal and urinary disorders
    HYPERTONIC BLADDER 2/381 (0.5%) 2 0/59 (0%) 0 0/183 (0%) 0 1/1 (100%) 1
    Respiratory, thoracic and mediastinal disorders
    ASTHMA 4/381 (1%) 6 0/59 (0%) 0 1/183 (0.5%) 1 1/1 (100%) 1
    COUGH 15/381 (3.9%) 18 2/59 (3.4%) 2 8/183 (4.4%) 9 1/1 (100%) 1
    Skin and subcutaneous tissue disorders
    RASH 9/381 (2.4%) 10 3/59 (5.1%) 3 8/183 (4.4%) 9 0/1 (0%) 0
    SKIN LESION 4/381 (1%) 4 3/59 (5.1%) 3 2/183 (1.1%) 2 0/1 (0%) 0
    Vascular disorders
    HYPERTENSION 62/381 (16.3%) 82 10/59 (16.9%) 13 26/183 (14.2%) 31 0/1 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Results Point of Contact

    Name/Title Dave Goldstraw
    Organization AstraZeneca Pharmaceuticals
    Phone +44 (0)1625 512415
    Email dave.goldstraw@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00805467
    Other Study ID Numbers:
    • C-935788-012
    • D4300C00021
    First Posted:
    Dec 9, 2008
    Last Update Posted:
    Jun 25, 2014
    Last Verified:
    May 1, 2014