Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38003   clinical trials with a EudraCT protocol, of which   6235   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A re-treatment safety study of radium-223 dichloride in subjects with castration-resistant prostate cancer with bone metastases who received an initial course of six doses of radium-223 dichloride 50 kBq/kg every four weeks

    Summary
    EudraCT number
    2013-003046-17
    Trial protocol
    SE   NO   FI   IT   ES   GB   DE  
    Global end of trial date
    12 Apr 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Mar 2018
    First version publication date
    12 Mar 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BAY88-8223/16506
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01934790
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Apr 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Apr 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the safety of re-treatment with up to 6 doses of radium-223 dichloride 50 kBq/kg given every 4 weeks in subjects with castration-resistant prostate cancer (CRPC) with bone metastases who received an initial course of 6 doses of radium-223 dichloride 50 kBq/kg.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Only after the subject voluntarily signed the informed consent form was he/she able to enter the study. If the subject was not capable of providing a signature, an oral statement of consent could have been given in the presence of a witness. Each subject was assured of the right to withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    22 Dec 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    7 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United States: 21
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    Israel: 7
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Norway: 4
    Worldwide total number of subjects
    44
    EEA total number of subjects
    16
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    13
    From 65 to 84 years
    26
    85 years and over
    5

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Overall, 59 subjects were enrolled into the study centers in 7 countries worldwide, from 22-Dec-2013 (first patient first visit) to 12-Apr-2017 (last patient last visit).

    Pre-assignment
    Screening details
    The study was conducted at 16 study centers that screened 59 subjects. Of them, 14 were screening failures and the remaining 45 subjects were assigned to treatment.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Arm description
    Subjects received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.
    Arm type
    Experimental

    Investigational medicinal product name
    Radium-223 dichloride
    Investigational medicinal product code
    BAY88-8223
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.

    Number of subjects in period 1
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Started
    44
    Entered active Follow up
    34
    Entered long term Follow up
    12 [1]
    Completed
    29
    Not completed
    15
         Radiological progression
    4
         Clinical progression
    6
         Adverse event, non-fatal
    3
         Consent withdrawn by subject
    2
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Due to database constraint, number of subjects entering each study phase was reported as milestones.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Reporting group description
    Subjects received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.

    Reporting group values
    Radium-223 dichloride (Xofigo, BAY88-8223) Total
    Number of subjects
    44 44
    Age categorical
    Units: Subjects
        < 65 years
    13 13
        >=65 years
    31 31
    Age continuous
    Units: years
        median (full range (min-max))
    71 (52 to 91) -
    Gender categorical
    Units: Subjects
        Female
    0 0
        Male
    44 44
    Baseline Eastern Cooperative Oncology Group (ECOG) Performance status (PS) score
    Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead).
    Units: Subjects
        ECOG PS score=0
    14 14
        ECOG PS score=1
    27 27
        ECOG PS score=2
    3 3
    Number of bone lesions
    Units: Subjects
        1-5
    18 18
        6-20
    15 15
        > 20, not a superscan
    6 6
        Superscan
    5 5
    Prostate specific antigen (PSA) - mean value
    Units: microgram per liter
        arithmetic mean (standard deviation)
    211.59 ± 452.84 -
    Total alkaline phosphatase (ALP) -mean value
    Units: Unit per liter
        arithmetic mean (standard deviation)
    122.60 ± 118.49 -
    Time from initial diagnosis of bone metastasis
    Units: Months
        median (full range (min-max))
    43.12 (7.6 to 172.4) -
    Time from initial diagnosis
    Units: Months
        median (full range (min-max))
    80.34 (11.8 to 287.9) -
    Time since initial treatment with radium-223 dichloride
    Units: Months
        median (full range (min-max))
    6.05 (1.2 to 17.1) -
    Prostate specific antigen (PSA) - median value
    Units: microgram per liter
        median (full range (min-max))
    67.66 (0.05 to 2349.04) -
    Total alkaline phosphatase (ALP) - median value
    Units: Unit per liter
        median (full range (min-max))
    85 (29 to 705) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Reporting group description
    Subjects received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections.

    Subject analysis set title
    Safety Analysis Set (SAF)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    All subjects who received at least one dose of study drug

    Subject analysis set title
    Active Follow-up Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects who were reported in the End of Treatment (EOT) electronic case report form (eCRF) as planning to participate in the active follow-up.

    Primary: Number of subjects with treatment-emergent adverse events (AEs)

    Close Top of page
    End point title
    Number of subjects with treatment-emergent adverse events (AEs) [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. A treatment-emergent adverse events (TEAE) is defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of radium-223 dichloride.
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [2]
    Units: Subjects
        number (not applicable)
    41
    Notes
    [2] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Primary: Number of subjects with treatment-emergent serious adverse events (SAEs)

    Close Top of page
    End point title
    Number of subjects with treatment-emergent serious adverse events (SAEs) [3]
    End point description
    TESAE occurred after the start of radium-223 dichloride treatment until 30 days after the last dose and results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly / birth defect; is another medically important serious event as judged by the investigator; or is an occurrence of leukemia, myelodysplastic syndrome, aplastic anemia, myelofibrosis, and primary bone cancer or any other new primary malignancy, such as acute myeloid leukemia.
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [4]
    Units: Subjects
        number (not applicable)
    13
    Notes
    [4] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Primary: Number of subjects with Radium-223 dichloride-related AEs in the active follow-up period

    Close Top of page
    End point title
    Number of subjects with Radium-223 dichloride-related AEs in the active follow-up period [5]
    End point description
    An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study.
    End point type
    Primary
    End point timeframe
    Up to 2 years after last treatment
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [6]
    Units: Subjects
        number (not applicable)
    1
    Notes
    [6] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Primary: Number of subjects with Radium-223 dichloride-related SAEs in the active follow-up period

    Close Top of page
    End point title
    Number of subjects with Radium-223 dichloride-related SAEs in the active follow-up period [7]
    End point description
    Treatment-related SAE is any SAE that, according to the investigator’s causality assessment, is possibly or probably related to treatment with radium-223 dichloride.
    End point type
    Primary
    End point timeframe
    Up to 2 years after last treatment
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [8]
    Units: Subjects
        number (not applicable)
    0
    Notes
    [8] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Primary: Number of subjects with high/low abnormalities in hematology variables at any visit after treatment start

    Close Top of page
    End point title
    Number of subjects with high/low abnormalities in hematology variables at any visit after treatment start [9]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [10]
    Units: Subjects
    number (not applicable)
        Eosinophils (GIGA/L) - High
    1
        Ery. Mean Corpuscular HGB Conc. (g/dL) - High
    1
        Ery. Mean Corpuscular Hemoglobin (pg) - High
    16
        Ery. Mean Corpuscular Volume (fL) - High
    22
        Leukocytes (GIGA/L) - High
    5
        Monocytes (GIGA/L) - High
    7
        Neutrophils (GIGA/L) - High
    9
        Platelets (GIGA/L) - High
    1
        Basophils (GIGA/L) - Low
    2
        Eosinophils (GIGA/L) - Low
    7
        Ery. Mean Corpuscular HGB Conc. (g/dL) - Low
    17
        Ery. Mean Corpuscular Hemoglobin (pg) - Low
    4
        Ery. Mean Corpuscular Volume (fL)
    3
        Erythrocytes (T/L) - Low
    43
        Hematocrit (%) - Low
    43
        Hemoglobin (g/dL) - Low
    43
        Leukocytes (GIGA/L) - Low
    21
        Lymphocytes (GIGA/L) - Low
    36
        Monocytes (GIGA/L) - Low
    2
        Neutrophils (GIGA/L) - Low
    10
        Platelets (GIGA/L) - Low
    11
    Notes
    [10] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Primary: Number of subjects with high/low abnormalities in biochemistry variables at any visit after treatment start

    Close Top of page
    End point title
    Number of subjects with high/low abnormalities in biochemistry variables at any visit after treatment start [11]
    End point description
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [12]
    Units: Subjects
    number (not applicable)
        Alanine Aminotransferase (U/L) - High
    2
        Alkaline Phosphatase (U/L) - High
    14
        Aspartate Aminotransferase (U/L) - High
    6
        Bilirubin (mg/dL) - High
    1
        Creatinine (mg/dL) - High
    7
        Sodium (mmol/L) - High
    6
        Alanine Aminotransferase (U/L) - Low
    4
        Albumin (g/dL) - Low
    10
        Aspartate Aminotransferase (U/L) - Low
    1
        Bilirubin (mg/dL) - Low
    4
        Creatinine (mg/dL) - Low
    7
        Sodium (mmol/L) - Low
    14
    Notes
    [12] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Primary: Number of subjects who discontinued Radium-223 dichloride treatment due to treatment emergent AEs or death

    Close Top of page
    End point title
    Number of subjects who discontinued Radium-223 dichloride treatment due to treatment emergent AEs or death [13]
    End point description
    An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended sign [including abnormal laboratory findings], symptom, or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. A treatment-emergent adverse events (TEAE) is defined as any event arising or worsening after the start of study drug administration until 30 days after the last administration of radium-223 dichloride.
    End point type
    Primary
    End point timeframe
    Up to 2.5 years
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed.
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [14]
    Units: Subjects
        number (not applicable)
    2
    Notes
    [14] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Radiological progression free survival (rPFS)

    Close Top of page
    End point title
    Radiological progression free survival (rPFS)
    End point description
    Radiological progression-free survival (rPFS) was defined as the time from the treatment start date to the date of radiological disease progression or death from any cause (if death occurred before such progression), as documented by the investigator. Subjects not experiencing death or radiological disease progression at the database cutoff for primary completion were censored at the last radiological disease progression assessment.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [15]
    Units: Months
        median (confidence interval 95%)
    9.9 (6.9 to 12.9)
    Notes
    [15] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to radiological bone progression

    Close Top of page
    End point title
    Time to radiological bone progression
    End point description
    Time to radiological bone progression was defined as the time (days) from the treatment start date to the date of radiological bone progression (according to the adapted PCWG2 [Prostate Cancer Clinical Trials Working Group 2] criteria), as documented by the investigator. Subjects not experiencing radiological bone progression at the database cutoff for primary completion were censored at the last radiological bone progression assessment. An entry of ‘99999’ indicates that the value could not be estimated due to censored values.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [16]
    Units: Months
        median (confidence interval 95%)
    99999 (9.9 to 99999)
    Notes
    [16] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Percentage of subjects with total alkaline phosphatase (ALP) response

    Close Top of page
    End point title
    Percentage of subjects with total alkaline phosphatase (ALP) response
    End point description
    Total alkaline phosphatase (ALP) response was defined as ≥ 30% reduction of the blood total ALP level compared with the baseline values. Total ALP response rate was defined as the number of subjects with total ALP response divided by the total number of subjects evaluable for total ALP response.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2.5 years
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [17]
    Units: Percentage of subjects
    number (confidence interval 95%)
        12 Week, n=33
    39.4 (22.9 to 57.9)
        24 Week, n=36
    30.6 (16.3 to 48.1)
        Anytime, n=44
    43.2 (28.3 to 59.0)
    Notes
    [17] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to total ALP progression

    Close Top of page
    End point title
    Time to total ALP progression
    End point description
    Total ALP progression was defined as a ≥ 25% increase above the nadir (lowest baseline or post-baseline) value to at least 1.5 x ULN (upper limit of normal). The time to total ALP progression was defined as the time (days) from the treatment start date to the date of first total ALP progression. Subjects not experiencing ALP progression at the database cutoff date, whether or not surviving, were censored at the last ALP laboratory assessment. An entry of ‘99999’ indicates that the value could not be estimated due to censored values.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [18]
    Units: Months
        median (confidence interval 95%)
    99999 (11.9 to 99999)
    Notes
    [18] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Percent change in total ALP

    Close Top of page
    End point title
    Percent change in total ALP
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 12, Week 24
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [19]
    Units: Percent change
    arithmetic mean (standard deviation)
        Week 12, n=33
    -17.1 ± 32.74
        Week 24, n=36
    -15.0 ± 35.10
    Notes
    [19] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Percentage of subjects with prostate specific antigen (PSA) response

    Close Top of page
    End point title
    Percentage of subjects with prostate specific antigen (PSA) response
    End point description
    Prostate specific antigen (PSA) response was defined as a ≥ 30% reduction of blood PSA level compared with the baseline value, confirmed by a second subsequent PSA value with a ≥ 30% reduction from baseline approximately 4 or more weeks later. Prostate specific antigen response rate was defined as the number of subjects with PSA response divided by the total number of subjects evaluable for PSA response.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2.5 years
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [20]
    Units: Percentage of subjects
    number (confidence interval 95%)
        12 Week, n=32
    6.3 (0.8 to 20.8)
        24 Week, n=36
    0 (0 to 9.7)
        Anytime, n=44
    9.1 (2.5 to 21.7)
    Notes
    [20] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to PSA progression

    Close Top of page
    End point title
    Time to PSA progression
    End point description
    Prostate specific antigen progression was defined as a ≥ 25% increase above the nadir (lowest baseline or post-baseline) value, and an increase in absolute value of ≥ 2 ng/mL above nadir. The time to PSA progression was defined as the time (days) from the treatment start date to the date of first PSA progression. Subjects without PSA progression as of the database cutoff for primary completion, whether or not surviving, were censored at the last PSA laboratory assessment.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [21]
    Units: Months
        median (confidence interval 95%)
    2.2 (1.8 to 3.1)
    Notes
    [21] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Overall survival

    Close Top of page
    End point title
    Overall survival
    End point description
    Overall survival (OS) was defined as the time (days) from the treatment start date to the date of death due to any cause. For subjects who were still alive or who were lost to follow-up as of the database cutoff date for the primary completion, OS was censored at the last known alive date on or prior to the database cutoff date.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [22]
    Units: Months
        median (confidence interval 95%)
    24.4 (14.9 to 28.6)
    Notes
    [22] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Percentage of subjects with pain improvement

    Close Top of page
    End point title
    Percentage of subjects with pain improvement
    End point description
    Pain improvement was defined in evaluable subjects (subjects with worst pain score [WPS] of 4 at baseline) as a 30% and 2-point decrease in WPS over 2 consecutive measurements conducted at least 4 weeks apart, without an increase in pain management. Pain improvement rate was the number of subjects with pain improvement, divided by the total number of evaluable subjects WPS was the mean of the WPS in the last 24 hours from the preceding 7 days.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2.5 years
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [23]
    Units: Percentage of subjects
    number (confidence interval 95%)
        12 Week, n=6
    0 (0 to 45.9)
        24 Week, n=8
    0 (0 to 36.9)
        Anytime, n=12
    8.3 (0.2 to 38.5)
    Notes
    [23] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to pain progression

    Close Top of page
    End point title
    Time to pain progression
    End point description
    Pain progression was defined in subjects evaluable for pain progression at baseline, i.e., subjects with a WPS of ≤ 7 at the baseline assessment. Pain assessment occurred daily for 1 week, beginning 1 week prior to each visit and including the day of the visit. An evaluable pain assessment interval required completion of a minimum of 4 out of 7 daily questions. Pain progression was defined as the occurrence of either a pain increase or an increase in pain management with respect to baseline, whichever occurred first. An entry of ‘99999’ indicates that the value could not be estimated due to censored values.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2.5 years
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [24]
    Units: Months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    Notes
    [24] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: Time to first symptomatic skeletal event (SSE)

    Close Top of page
    End point title
    Time to first symptomatic skeletal event (SSE)
    End point description
    Time to first symptomatic skeletal event (SSE) is the time (days) from the treatment start date to the first SSE on or following the start date. Subjects not experiencing an SSE at the database cutoff date for primary completion, whether or not surviving, were censored at the last assessment for SSEs. An entry of ‘99999’ indicates that the value could not be estimated due to censored values.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [25]
    Units: Months
        median (confidence interval 95%)
    16.7 (9.7 to 99999)
    Notes
    [25] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Other pre-specified: SSE-free survival

    Close Top of page
    End point title
    SSE-free survival
    End point description
    The SSE-FS is the time (days) from the treatment start date to the first SSE on or following the start date or death, whichever occurred first. Subjects not experiencing death or an SSE at the database cutoff date for primary completion were censored at the last assessment for SSEs.
    End point type
    Other pre-specified
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [26]
    Units: Months
        median (confidence interval 95%)
    12.8 (9.5 to 24.4)
    Notes
    [26] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Post-hoc: Number of subjects with new SSE related AEs during the follow-up period

    Close Top of page
    End point title
    Number of subjects with new SSE related AEs during the follow-up period
    End point description
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [27]
    Units: Subjects
        number (not applicable)
    0
    Notes
    [27] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Post-hoc: Number of subjects with new primary malignancies during study treatment or follow-up period

    Close Top of page
    End point title
    Number of subjects with new primary malignancies during study treatment or follow-up period
    End point description
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [28]
    Units: Subjects
        number (not applicable)
    1
    Notes
    [28] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Post-hoc: Number of deaths during study treatment or follow-up period

    Close Top of page
    End point title
    Number of deaths during study treatment or follow-up period
    End point description
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    44 [29]
    Units: Subjects
    number (not applicable)
        During Treatment Period
    1
        During Active follow-up Period
    23
        During Long-term follow-up Period
    4
    Notes
    [29] - Safety Analysis Set (SAF)
    No statistical analyses for this end point

    Post-hoc: Number of subjects with significant meaningful changes for clinical laboratory NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) toxicity grades during the follow-up period

    Close Top of page
    End point title
    Number of subjects with significant meaningful changes for clinical laboratory NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) toxicity grades during the follow-up period
    End point description
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [30]
    Units: Subjects
        number (not applicable)
    0
    Notes
    [30] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Post-hoc: Number of subjects with body weight changes during the follow-up period

    Close Top of page
    End point title
    Number of subjects with body weight changes during the follow-up period
    End point description
    Subjects were counted once during active follow-up for both increases (using the maximum body weight) and decreases (using the minimum body weight).
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [31]
    Units: Subjects
    number (not applicable)
        Increases < 5%
    23
        Increases 5-10%
    4
        Increases > 10%
    0
        Decreases < 5%
    13
        Decreases 5-10%
    9
        Decreases > 10%
    5
    Notes
    [31] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Post-hoc: Number of subjects with Eastern Cooperative Oncology Group (ECOG) performance status (PS) score worsened to >=3 during the follow-up period

    Close Top of page
    End point title
    Number of subjects with Eastern Cooperative Oncology Group (ECOG) performance status (PS) score worsened to >=3 during the follow-up period
    End point description
    End point type
    Post-hoc
    End point timeframe
    Up to 2 years after last treatment
    End point values
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Number of subjects analysed
    34 [32]
    Units: Subjects
        number (not applicable)
    4
    Notes
    [32] - Active Follow-up Analysis Set
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From start of study treatment until 30 days after last dose of study medication up to 2.5 years
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Reporting group description
    Subjects received intravenous (IV) injection of radium-223 dichloride 50 kBq/kg body weight every 4 weeks up to 6 injections

    Serious adverse events
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 44 (29.55%)
         number of deaths (all causes)
    28
         number of deaths resulting from adverse events
    1
    Vascular disorders
    Peripheral ischaemia
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Stomatitis radiation
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Dementia Alzheimer's type
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Glaucoma
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Uveitis
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Gastrointestinal disorders
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteonecrosis of jaw
         subjects affected / exposed
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Radium-223 dichloride (Xofigo, BAY88-8223)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    35 / 44 (79.55%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 44 (13.64%)
         occurrences all number
    6
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    8
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 44 (13.64%)
         occurrences all number
    6
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    4
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    4
    Fatigue
         subjects affected / exposed
    12 / 44 (27.27%)
         occurrences all number
    12
    Oedema peripheral
         subjects affected / exposed
    4 / 44 (9.09%)
         occurrences all number
    5
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Abdominal pain
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Diarrhoea
         subjects affected / exposed
    9 / 44 (20.45%)
         occurrences all number
    11
    Nausea
         subjects affected / exposed
    11 / 44 (25.00%)
         occurrences all number
    13
    Vomiting
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    8
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 44 (13.64%)
         occurrences all number
    7
    Back pain
         subjects affected / exposed
    5 / 44 (11.36%)
         occurrences all number
    5
    Bone pain
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Musculoskeletal pain
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Myalgia
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Spinal pain
         subjects affected / exposed
    3 / 44 (6.82%)
         occurrences all number
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    8 / 44 (18.18%)
         occurrences all number
    9

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Nov 2013
    The following changes were made: - Terminology changes, including the following which impacted endpoints: the pain endpoint was changed from pain response to pain improvement; skeletal-related event was changed to SSE. - Clarification of selection criteria of subjects for whom re-treatment was indicated, including baseline rising PSA level and substantial worsening of pain. - Specified that a separate, extended safety follow-up study protocol is being implemented and will capture the long-term follow-up of subjects on this study. - The definition of bone progression was revised based on the adapted PCWG2 criteria for consistency across the radium-223 dichloride program. - Assessment schedules for multiple variables were clarified or updated based on current regulatory requirements and recommendations.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA