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    Clinical Trial Results:
    A Phase II, Open-label Study to Assess the Efficacy, Safety, and Tolerability of AZD4635 in Combination with Durvalumab and in Combination with Cabazitaxel and Durvalumab in Patients Who Have Progressive Metastatic Castrate-Resistant Prostate Cancer (AARDVARC)

    Summary
    EudraCT number
    		 2020-000209-10
    Trial protocol
    		 BE   DE   FR   DK   NL  
    Global end of trial date
    08 Aug 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    23 Aug 2023
    First version publication date
    23 Aug 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D8731C00002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04495179
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    NA, NA, United States, NA
    Public contact
    Global Clinical Head, AstraZeneca Clinical Study Information Center, +1 87724094 79, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Head, AstraZeneca Clinical Study Information Center, +1 87724094 79, information.center@astrazeneca.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
    29 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy (as assessed by radiographic progression free survival [rPFS]) of AZD4635 plus durvalumab and separately of AZD4635 plus durvalumab plus cabazitaxel in participants with metastatic castrate-resistant prostate cancer (mCRPC).
    Protection of trial subjects
    This study was conducted in accordance with the protocol and with the consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organisations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable International Council for Harmonisation Good Clinical Practice (ICH GCP) Guidelines, and the applicable laws and regulations
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Aug 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United States: 11
    Worldwide total number of subjects
    30
    EEA total number of subjects
    15
    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)
    8
    From 65 to 84 years
    22
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled in this study from 04-August-2020 to 08-August-2022.

    Pre-assignment
    Screening details
    		 Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm A: AZD4635 + durvalumab
    Arm description
    		 Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AZD4635
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered AZD4635 75 mg tablets orally daily.

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Concentrate for solution for injection
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Participants were administered durvalumab 1500 mg intravenously (IV) every 4 weeks (Q4W).

    Arm title
    		 Arm B: AZD4635 + durvalumab + cabazitaxel
    Arm description
    		 Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W
    Arm type
    		 Experimental

    Investigational medicinal product name
    AZD4635
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered AZD4635 75 mg tablets orally daily.

    Investigational medicinal product name
    Cabazitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Concentrate for solution for injection
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Participants were administered cabazitaxel 20 or 25 mg/m2 intravenously every 3 weeks (Q3W).

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants were administered durvalumab 1500 mg intravenously every 4 weeks.

    Number of subjects in period 1
    		Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Started
    2
    28
    Completed
    0
    0
    Not completed
    2
    28
         Adverse event, serious fatal
    -
    4
         Consent withdrawn by subject
    2
    4
         Adverse event, non-fatal
    -
    1
         Study terminated by sponsor
    -
    18
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A: AZD4635 + durvalumab
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks.

    Reporting group title
    Arm B: AZD4635 + durvalumab + cabazitaxel
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W

    Reporting group values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel Total
    Number of subjects
    		 2 28 30
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 1 7 8
        From 65-84 years
    		 1 21 22
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 0 ( 0 ) 68.0 ( 8.18 ) -
    Sex/Gender, Customized
    Units: Participants
        Male
    		 2 28 30
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 0 5 5
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 0 19 19
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 2 4 6
    Ethnicity (NIH/OMB)
    The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
    Units: Subjects
        Hispanic or Latino
    		 0 4 4
        Not Hispanic or Latino
    		 0 21 21
        Unknown or Not Reported
    		 2 3 5

    End points

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    End points reporting groups
    Reporting group title
    Arm A: AZD4635 + durvalumab
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks.

    Reporting group title
    Arm B: AZD4635 + durvalumab + cabazitaxel
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W

    Primary: Radiographic Progression Free Survival (rPFS) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in patients with metastatic castrate-resistant prostate cancer (mCRPC)

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    End point title
    		 Radiographic Progression Free Survival (rPFS) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in patients with metastatic castrate-resistant prostate cancer (mCRPC) [1]
    End point description
    rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria [bone] or death from any cause, whichever occurred first.
    End point type
    Primary
    End point timeframe
    From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)
    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: Statistical Analyses were not performed for these Outcome Measures as this study is non-comparative.
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [2]
    28 [3]
    Units: months
        median (confidence interval 95%)
    ( to )
    5.8 (4.2 to 9999.9999)
    Notes
    [2] - The data for Arm A was not calculated because of a patient identification risk.
    [3] - "9999.9999" indicates that a upper limit was not calculated due to not enough events at later times.
    No statistical analyses for this end point

    Secondary: rPFS by adenosine (ADO) signalling gene expression in high and low subgroups to determine the efficacy of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC

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    End point title
    		 rPFS by adenosine (ADO) signalling gene expression in high and low subgroups to determine the efficacy of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC
    End point description
    rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurred first.
    End point type
    Secondary
    End point timeframe
    From first dose to first documented progression or death from any cause (whichever comes first), up to two years
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [4]
    27
    Units: Participants
        High ADO
    14
        Low ADO
    13
    Notes
    [4] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Overall survival (OS) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC

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    End point title
    		 Overall survival (OS) in each arm separately to determine the efficacy of AZD4635 plus durvalumab and of AZD4635 plus durvalumab plus cabazitaxel in participants with mCRPC
    End point description
    OS was defined as the time from first dose until death due to any cause regardless of whether the participant withdrew from study treatment or received another anti-cancer therapy.
    End point type
    Secondary
    End point timeframe
    Arm A and B: Every 90 days from the last dose of study drug up to 2 years
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [5]
    28 [6]
    Units: months
        median (confidence interval 95%)
    ( to )
    9999.9999 (7.9 to 9999.9999)
    Notes
    [5] - The data for Arm A was not calculated because of a patient identification risk.
    [6] - "9999.9999" indicates that these values were not calculated as less than 50% patients died.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Objective Response in Subjects with MCRPC who received AZD4635 Plus Durvalumab Plus Cabazitaxel

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    End point title
    		 Number of Subjects with Objective Response in Subjects with MCRPC who received AZD4635 Plus Durvalumab Plus Cabazitaxel
    End point description
    Confirmed ORR was defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) using overall radiographic response assessed by RECIST v1.1 and PCWG-3 criteria (bone), and was based on a subset of all treated participants with measurable disease at baseline per the site Investigator.
    End point type
    Secondary
    End point timeframe
    From first dose to first documented progression or death from any cause (whichever comes first), up to two years
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [7]
    28
    Units: Participants
    2
    Notes
    [7] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Number of Subjects with Prostate-specifin Antigen (PSA50) Response in Subjects with MCRPC who Received AZD4635 Plus Durvalumab Plus Cabazitaxel

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    End point title
    		 Number of Subjects with Prostate-specifin Antigen (PSA50) Response in Subjects with MCRPC who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
    End point description
    Confirmed PSA50 response is defined as the proportion of participants who achieved a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and was based on PSA evaluable participants (dosed participants with an abnormal baseline PSA [≥1 ng/mL]).
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [8]
    28
    Units: Participants
    5
    Notes
    [8] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Change from baseline in worst pain in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)

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    End point title
    		 Change from baseline in worst pain in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)
    End point description
    "Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70. Note: None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint. n = Number of participants included in analysis
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [9]
    28 [10]
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Baseline (n = 14)
    ( )
    3.4 ( 2.44 )
        Cycle 1 Day 1 (n = 0)
    ( )
    9999.9999 ( 9999.9999 )
        Cycle 2 Day 1 (n = 11)
    ( )
    -1.6 ( 2.94 )
        Cycle 3 Day 1 (n = 13)
    ( )
    -0.3 ( 4.40 )
        Cycle 4 Day 1 (n = 9)
    ( )
    -1.6 ( 2.88 )
        Cycle 5 Day 1 (n = 7)
    ( )
    -2.1 ( 3.58 )
        Cycle 6 Day 1 (n = 8)
    ( )
    -1.9 ( 3.00 )
        Cycle 7 Day 1 (n = 8)
    ( )
    1.0 ( 1.85 )
        Cycle 8 Day 1 (n = 6)
    ( )
    -1.7 ( 2.66 )
        Cycle 9 Day 1 (n = 5)
    ( )
    -0.2 ( 2.17 )
    Notes
    [9] - The data for Arm A was not calculated because of a patient identification risk.
    [10] - Here, arbitrary value 9999.9999 indicates that the values are not available.
    No statistical analyses for this end point

    Secondary: Change from baseline in average pain in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)

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    End point title
    		 Change from baseline in average pain in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)
    End point description
    "Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70. Note: None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint. n = Number of participants included in analysis
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [11]
    28 [12]
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Baseline (n = 14)
    ( )
    2.3 ( 2.09 )
        Cycle 1 Day 1 (n = 0)
    ( )
    9999.9999 ( 9999.9999 )
        Cycle 2 Day 1 (n = 11)
    ( )
    -1.3 ( 1.19 )
        Cycle 3 Day 1 (n = 13)
    ( )
    0.6 ( 3.15 )
        Cycle 4 Day 1 (n = 9)
    ( )
    -0.9 ( 1.27 )
        Cycle 5 Day 1 (n = 7)
    ( )
    -1.6 ( 2.15 )
        Cycle 6 Day 1 (n = 8)
    ( )
    -1.4 ( 1.51 )
        Cycle 7 Day 1 (n =8)
    ( )
    0.0 ( 1.41 )
        Cycle 8 Day 1 (n = 6)
    ( )
    -0.8 ( 1.47 )
        Cycle 9 Day 1 (n = 5)
    ( )
    -1.2 ( 0.84 )
    Notes
    [11] - The data for Arm A was not calculated because of a patient identification risk.
    [12] - Here, arbitrary value 9999.9999 indicates that the values are not available.
    No statistical analyses for this end point

    Secondary: Change from baseline in pain interference in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)

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    End point title
    		 Change from baseline in pain interference in the daily activities scales of the Brief Pain Inventory – Short Form (BPI-SF)
    End point description
    "Worst pain" and "Average pain" are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). "Interference Pain" is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the "Interference Score" can be from 0 to 70. Note: None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint. n = Number of participants included in analysis
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [13]
    28 [14]
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Baseline (n = 14)
    ( )
    8.0 ( 8.47 )
        Cycle 1 Day 1 (n = 0)
    ( )
    9999.9999 ( 9999.9999 )
        Cycle 2 Day 1 (n = 11)
    ( )
    2.5 ( 13.90 )
        Cycle 3 Day 1 (n = 13)
    ( )
    12.3 ( 18.96 )
        Cycle 4 Day 1 (n = 9)
    ( )
    4.9 ( 12.73 )
        Cycle 5 Day 1 (n = 7)
    ( )
    1.3 ( 5.19 )
        Cycle 6 Day 1 (n = 8)
    ( )
    2.0 ( 8.40 )
        Cycle 7 Day 1 (n = 8)
    ( )
    8.1 ( 9.93 )
        Cycle 8 Day 1 (n = 6)
    ( )
    7.2 ( 13.98 )
        Cycle 9 Day 1 (n =5)
    ( )
    5.4 ( 15.16 )
    Notes
    [13] - The data for Arm A was not calculated because of a patient identification risk.
    [14] - Here, arbitrary value 9999.9999 indicates that the values are not available.
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Progressed Based on BPI-SF Item 3

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    End point title
    		 Number of Subjects Who Progressed Based on BPI-SF Item 3
    End point description
    Pain progression was assessed using BPI-SF.
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 12 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 12 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [15]
    28
    Units: Participants
    1
    Notes
    [15] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Change from baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as derived from 6 items, the FAPSI-8 from 8 items within the FACT-P and the Prostate Cancer Symptoms (PCS), from the 12 items in the prostrate-specific module of the FACT-P

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    End point title
    		 Change from baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as derived from 6 items, the FAPSI-8 from 8 items within the FACT-P and the Prostate Cancer Symptoms (PCS), from the 12 items in the prostrate-specific module of the FACT-P
    End point description
    The Functional Assessment of Cancer Therapy-Prostate (FACT-P) will be used to measure health related quality of life (HRQL) in men with prostate cancer. It consists of 4 subscales (physical, emotional, functional and social/family well-being) plus a 12-item prostate-specific module, the PCS subscale, which highlights concerns specific to participants with prostate cancer. Each question in the FACT-P questionnaires has a choice of 5 responses, “Not at all”, “A little bit”, “Somewhat”, “Quite a bit” and “Very much”. The scores range from 0 (“Not at all”) to 4 (“Very much”) for positively phrased questions. Negatively phrased questions have a reverse scoring, from 0 (“Very much”) to 4 (“Not at all”). n = Number of participants included in analysis Note: None of the 10 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint.
    End point type
    Secondary
    End point timeframe
    Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [16]
    28 [17]
    Units: Score on a Scale
    arithmetic mean (standard deviation)
        Baseline (n = 10)
    ( )
    16.6 ( 2.88 )
        Cycle 1 Day 1 (n = 0)
    ( )
    9999.9999 ( 9999.9999 )
        Cycle 2 Day 1 (n = 7)
    ( )
    1.9 ( 1.68 )
        Cycle 3 Day 1 (n = 9)
    ( )
    -0.7 ( 5.52 )
        Cycle 4 Day 1 (n = 7)
    ( )
    -0.1 ( 3.34 )
        Cycle 5 Day 1 (n = 5)
    ( )
    0.6 ( 3.36 )
        Cycle 6 Day 1 (n = 6)
    ( )
    1.5 ( 1.38 )
        Cycle 7 Day 1 (n = 7)
    ( )
    0.0 ( 3.92 )
        Cycle 8 Day 1 (n = 5)
    ( )
    -1.8 ( 4.15 )
        Cycle 9 Day 1 (n = 4)
    ( )
    -3.0 ( 4.55 )
    Notes
    [16] - The data for Arm A was not calculated because of a patient identification risk.
    [17] - Here, arbitrary value 9999.9999 indicates that the values are not available.
    No statistical analyses for this end point

    Secondary: Maximum observed plasma concentration (Cmax)

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    End point title
    		 Maximum observed plasma concentration (Cmax)
    End point description
    Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [18]
    15
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    483.0 ( 231.1 )
    Notes
    [18] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Terminal half-life (t1/2λz)

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    End point title
    		 Terminal half-life (t1/2λz)
    End point description
    Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [19]
    13
    Units: hour (h)
        arithmetic mean (standard deviation)
    ( )
    8.87 ( 4.82 )
    Notes
    [19] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast)

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    End point title
    		 Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast)
    End point description
    Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [20]
    15
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    ( )
    2787 ( 1056 )
    Notes
    [20] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration time curve from zero to 24 hours [AUC(0-24)]

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    End point title
    		 Area under the plasma concentration time curve from zero to 24 hours [AUC(0-24)]
    End point description
    Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [21]
    14
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    ( )
    2874 ( 1084 )
    Notes
    [21] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf)

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    End point title
    		 Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf)
    End point description
    Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [22]
    13
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    ( )
    3311 ( 1272 )
    Notes
    [22] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Apparent volume of distribution during the terminal phase (Vz/F)

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    End point title
    		 Apparent volume of distribution during the terminal phase (Vz/F)
    End point description
    Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
    End point type
    Secondary
    End point timeframe
    Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [23]
    13
    Units: Litre (L)
        arithmetic mean (standard deviation)
    ( )
    334.6 ( 254.4 )
    Notes
    [23] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Secondary: Number of subjects with serious and non-serious adverse events

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    End point title
    		 Number of subjects with serious and non-serious adverse events
    End point description
    Safety and tolerability of each treatment regimen were assessed in participants with mCRPC.
    End point type
    Secondary
    End point timeframe
    Arm A: From Screening up to 14 months (Each cycle was 28 days in length); Arm B: From Screening up to 14 months (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length)
    End point values
    		 Arm A: AZD4635 + durvalumab Arm B: AZD4635 + durvalumab + cabazitaxel
    Number of subjects analysed
    0 [24]
    28
    Units: Participants
        Any Adverse Event (AE)
    28
        Any AE possibly related to treatment
    28
        Any AE possibly related to AZD4635
    23
        Any AE possibly related to Durvalumab
    20
        Any AE possibly related to Cabazitaxel
    28
        Any AE of CTCAE grade 3 or higher
    24
        Any AE of CTCAE grade 3/higher treatment-related
    20
        Any AE of CTCAE grade 3 or higher AZD4635-related
    9
        Any AE of CTCAE grade 3/higher Durvalumab-related
    9
        Any AE of CTCAE grade 3/higher Cabazitaxel-related
    19
        Any Adverse Event of Special Interest - Durvalumab
    17
        Any possibly related AESI for Durvalumab
    10
        Any AE with outcome = death
    2
        Any AE with death possibly related to treatment
    1
        Any Serious Adverse Event (SAE) (including death)
    19
        Any SAE (including death) treatment-related
    12
        Any SAE leading to discontinuation of AZD4635
    4
        Any SAE leading to stopping of AZD4635 related
    1
        Any AE leading to discontinuation of AZD4635
    5
        Any AE leading to dose reduction of AZD4635
    4
        Any AE leading to dose interruption of AZD4635
    15
        Any AE leading to discontinuation of Durvalumab
    4
        Any AE leading to dose interruption of Durvalumab
    5
        Any AE leading to discontinuation of Cabazitaxel
    7
        Any AE leading to dose reduction of Cabazitaxel
    4
        Any AE leading to dose interruption of Cabazitaxel
    8
        Any other significant AEs
    0
    Notes
    [24] - The data for Arm A was not calculated because of a patient identification risk.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-Cause Mortality: Up to 2 years; Serious and/or other adverse events: From Screening up to 14 months (Each cycle was 28 days in length) for Arm A (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length) for Arm B.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Arm B: AZD4635 + durvalumab + cabazitaxel
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W

    Reporting group title
    Arm A: AZD4635 + durvalumab
    Reporting group description
    		 Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks.

    Serious adverse events
    		 Arm B: AZD4635 + durvalumab + cabazitaxel Arm A: AZD4635 + durvalumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 28 (67.86%)
    2 / 2 (100.00%)
         number of deaths (all causes)
    7
    2
         number of deaths resulting from adverse events
    Investigations
    Neutrophil Count Decreased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile Neutropenia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute Post Hemorrhagic Anemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal Haemorrhage
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Cystitis Haemorrhagic
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 2 (50.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myositis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureteritis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm B: AZD4635 + durvalumab + cabazitaxel Arm A: AZD4635 + durvalumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 28 (100.00%)
    2 / 2 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Hypertension
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    10 / 28 (35.71%)
    1 / 2 (50.00%)
         occurrences all number
    15
    1
    Chills
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    5 / 28 (17.86%)
    2 / 2 (100.00%)
         occurrences all number
    7
    2
    Pyrexia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Pain
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Reproductive system and breast disorders
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 2 (50.00%)
         occurrences all number
    3
    3
    Psychiatric disorders
    Depression
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Insomnia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Amylase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 28 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 28 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Lipase increased
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Neutrophil count decreased
         subjects affected / exposed
    4 / 28 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    8
    0
    Weight decreased
         subjects affected / exposed
    4 / 28 (14.29%)
    2 / 2 (100.00%)
         occurrences all number
    7
    2
    White blood cell count decreased
         subjects affected / exposed
    4 / 28 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 28 (17.86%)
    1 / 2 (50.00%)
         occurrences all number
    5
    2
    Headache
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Dysgeusia
         subjects affected / exposed
    6 / 28 (21.43%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    Neuropathy peripheral
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 28 (50.00%)
    1 / 2 (50.00%)
         occurrences all number
    19
    4
    Neutropenia
         subjects affected / exposed
    6 / 28 (21.43%)
    0 / 2 (0.00%)
         occurrences all number
    12
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 28 (14.29%)
    1 / 2 (50.00%)
         occurrences all number
    5
    1
    Constipation
         subjects affected / exposed
    8 / 28 (28.57%)
    1 / 2 (50.00%)
         occurrences all number
    8
    1
    Diarrhoea
         subjects affected / exposed
    14 / 28 (50.00%)
    2 / 2 (100.00%)
         occurrences all number
    21
    4
    Dyspepsia
         subjects affected / exposed
    4 / 28 (14.29%)
    0 / 2 (0.00%)
         occurrences all number
    5
    0
    Dry mouth
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 2 (50.00%)
         occurrences all number
    2
    1
    Oral pain
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    17 / 28 (60.71%)
    1 / 2 (50.00%)
         occurrences all number
    20
    1
    Vomiting
         subjects affected / exposed
    9 / 28 (32.14%)
    0 / 2 (0.00%)
         occurrences all number
    12
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Pruritus
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    3
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    5 / 28 (17.86%)
    0 / 2 (0.00%)
         occurrences all number
    7
    0
    Urinary retention
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    9 / 28 (32.14%)
    0 / 2 (0.00%)
         occurrences all number
    11
    0
    Back pain
         subjects affected / exposed
    5 / 28 (17.86%)
    1 / 2 (50.00%)
         occurrences all number
    5
    1
    Flank pain
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Muscle spasms
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Muscular weakness
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    6
    0
    Myalgia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    Pain in extremity
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    6 / 28 (21.43%)
    1 / 2 (50.00%)
         occurrences all number
    7
    2
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Decreased appetite
         subjects affected / exposed
    7 / 28 (25.00%)
    2 / 2 (100.00%)
         occurrences all number
    8
    2
    Hyperkalaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Hyperuricaemia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Hypocalcaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0
    Hypophosphataemia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 2 (0.00%)
         occurrences all number
    4
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Sep 2020
    The global protocol was amended to address comments received from various health authorities in the EU.
    24 Nov 2020
    The global protocol was amended due to the Sponsor’s decision to close enrolment in Arm A.

    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.
    The arbitrary value 9999.9999 indicates that the parameter was not measured.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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