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    Clinical Trial Results:
    A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery

    Summary
    EudraCT number
    2018-004237-32
    Trial protocol
    BE   HU   PL   PT   BG   ES   GR   LT   IT  
    Global end of trial date
    06 Apr 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Apr 2022
    First version publication date
    22 Apr 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    70033093THR2001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03891524
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920 Route 202, South Raritan, United States, 08869
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, clinicaltrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, clinicaltrialsEU@its.jnj.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
    06 Apr 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis (DVT) [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism (PE), or any death) during the treatment period.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. The safety evaluations included adverse events,including non-serious adverse events, serious adverse events, adverse events of interest (that is, bleeding events, liver enzyme elevations and clinical liver events, and wound or joint complications), clinical laboratory tests (that is, hematology, clinical chemistry, urinalysis), and physical examinations.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    17 Jun 2019
    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
    Argentina: 47
    Country: Number of subjects enrolled
    Belgium: 49
    Country: Number of subjects enrolled
    Bulgaria: 77
    Country: Number of subjects enrolled
    Brazil: 8
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Spain: 87
    Country: Number of subjects enrolled
    Greece: 81
    Country: Number of subjects enrolled
    Hungary: 107
    Country: Number of subjects enrolled
    Israel: 59
    Country: Number of subjects enrolled
    Italy: 10
    Country: Number of subjects enrolled
    Japan: 134
    Country: Number of subjects enrolled
    Poland: 217
    Country: Number of subjects enrolled
    Portugal: 79
    Country: Number of subjects enrolled
    Russian Federation: 20
    Country: Number of subjects enrolled
    Turkey: 23
    Country: Number of subjects enrolled
    Ukraine: 84
    Country: Number of subjects enrolled
    United States: 155
    Worldwide total number of subjects
    1242
    EEA total number of subjects
    707
    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)
    409
    From 65 to 84 years
    817
    85 years and over
    16

    Subject disposition

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    Recruitment
    Recruitment details
    No text entered

    Pre-assignment
    Screening details
    A total of 1,242 subjects were randomized and included in the ITT population.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    JNJ-70033093 25 mg Once Daily + Placebo
    Arm description
    Subjects received JNJ-70033093 25 mg (1*25 milligrams [mg] capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    JNJ-70033093 25 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) once daily.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 1 placebo capsule orally in the morning and 2 placebo capsules in the evening.

    Arm title
    JNJ-70033093 50 mg once daily + Placebo
    Arm description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 matching placebo capsules orally.

    Investigational medicinal product name
    JNJ-70033093 50 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules orally in the morning) once daily.

    Arm title
    JNJ-70033093 25 mg + Placebo Twice daily (BID)
    Arm description
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 1 matching placebo capsule orally, twice daily.

    Investigational medicinal product name
    JNJ-70033093 25 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) orally twice daily.

    Arm title
    JNJ-70033093 50 mg BID
    Arm description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    JNJ-70033093 50 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules) BID orally.

    Arm title
    JNJ-70033093 200 mg Once Daily + Placebo
    Arm description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 2 matching placebo capsules orally, in the evening.

    Investigational medicinal product name
    JNJ-70033093 200 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules in the morning) orally once daily.

    Arm title
    JNJ-70033093 100 mg + Placebo BID
    Arm description
    Subjects received JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 1 matching placebo capsule BID orally.

    Investigational medicinal product name
    JNJ-70033093 100 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 100 mg (1*100 mg capsule) BID orally.

    Arm title
    JNJ-70033093 200 mg BID
    Arm description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days.
    Arm type
    Experimental

    Investigational medicinal product name
    JNJ-70033093 200 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules) BID orally.

    Arm title
    Enoxaparin 40 mg Once Daily
    Arm description
    Subjects received enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
    Arm type
    Active comparator

    Investigational medicinal product name
    Enoxaparin 40 mg
    Investigational medicinal product code
    Other name
    BMS-986177
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received enoxaparin 40 mg once daily subcutaneously.

    Number of subjects in period 1
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Started
    34
    150
    153
    150
    149
    152
    153
    301
    Safety analysis set
    33 [1]
    150
    148 [2]
    148 [3]
    147
    149 [4]
    148 [5]
    296 [6]
    Completed
    34
    149
    151
    149
    147
    150
    151
    299
    Not completed
    0
    1
    2
    1
    2
    2
    2
    2
         Adverse event, serious fatal
    -
    -
    -
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    -
    1
    2
    1
    2
    2
    2
    1
    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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.
    [2] - 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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.
    [3] - 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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.
    [4] - 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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.
    [5] - 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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.
    [6] - 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: Among 1242 intent to treat (ITT) subjects,1,219 subjects received at least one dose of study drug and were included in the safety analysis set.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    JNJ-70033093 25 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 25 mg (1*25 milligrams [mg] capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg once daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 25 mg + Placebo Twice daily (BID)
    Reporting group description
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg BID
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 100 mg + Placebo BID
    Reporting group description
    Subjects received JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg BID
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    Enoxaparin 40 mg Once Daily
    Reporting group description
    Subjects received enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

    Reporting group values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily Total
    Number of subjects
    34 150 153 150 149 152 153 301 1242
    Age categorical
    Units: Subjects
        From 50-64 years
    9 51 47 43 51 55 49 104 409
        65 years and over
    25 99 106 107 98 97 104 197 833
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    68.1 ( 5.74 ) 67.9 ( 8.03 ) 68.4 ( 8.49 ) 68.8 ( 8.17 ) 68 ( 8.25 ) 67 ( 8 ) 68.6 ( 7.76 ) 67.8 ( 7.97 ) -
    Sex: Female, Male
    Units: subjects
        Female
    24 107 113 108 108 102 106 208 876
        Male
    10 43 40 42 41 50 47 93 366

    End points

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    End points reporting groups
    Reporting group title
    JNJ-70033093 25 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 25 mg (1*25 milligrams [mg] capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg once daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 25 mg + Placebo Twice daily (BID)
    Reporting group description
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg BID
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 100 mg + Placebo BID
    Reporting group description
    Subjects received JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg BID
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    Enoxaparin 40 mg Once Daily
    Reporting group description
    Subjects received enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

    Subject analysis set title
    Female
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Male
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Participants received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Age: Less than or Equal to (<=) 68 years
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Age: Greater than (>) 68 years
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Weight: Less than or Equal to (<=) 82 kilograms (kg)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Weight: Greater than (>) 82 kg
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Creatinine clearance (CRCL): Less than (<) 90
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    CRCL: Greater than or equal to (>=) 90
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 (either 25 mg, 50 mg, 100 mg or 200 mg) once daily or twice daily orally for 10 to 14 postoperative days.

    Subject analysis set title
    Overall
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects received JNJ-70033093 ( either 25 mg, 50 mg, 100 mg or 200 mg ) once daily or twice daily orally for 10 to 14 postoperative days.

    Primary: Number of Subjects with Total Venous Thromboembolism (VTE) (CEC-adjudicated)

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    End point title
    Number of Subjects with Total Venous Thromboembolism (VTE) (CEC-adjudicated) [1]
    End point description
    Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death. The modified Intent-to-treat (mITT) analysis set included all intent-to-treat (ITT) subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic proximal DVT, PE or death as adjudicated by the CEC.
    End point type
    Primary
    End point timeframe
    Up to Day 14
    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 was done, no inferential statistical analysis was performed.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    127
    129
    124
    123
    134
    131
    252
    Units: subjects
    7
    30
    27
    14
    8
    12
    10
    54
    No statistical analyses for this end point

    Secondary: Number of Subjects with any Bleeding Event (CEC-adjudicated)

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    End point title
    Number of Subjects with any Bleeding Event (CEC-adjudicated)
    End point description
    Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC. The safety analysis set was a subset of the intent to treat (ITT) analysis set, consisting of all ITT subjects who received at least 1 dose (partial or complete) of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 14; Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    8
    2
    7
    11
    7
    6
    12
        Up to Day 52
    0
    8
    2
    7
    11
    7
    6
    12
    No statistical analyses for this end point

    Secondary: Number of Subjects with Total VTE (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Subjects with Total VTE (CEC-adjudicated) Up to Day 52
    End point description
    Total VTE was defined as the composite of CEC-adjudicated proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death. The mITT analysis set included all the subjects in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Here,‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    253
    Units: subjects
    7
    30
    27
    14
    8
    12
    10
    54
    No statistical analyses for this end point

    Secondary: Number of Subjects With Composite of Major and Clinically Relevant Non-Major CRNM Bleeding Events (CEC-adjudicated)

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    End point title
    Number of Subjects With Composite of Major and Clinically Relevant Non-Major CRNM Bleeding Events (CEC-adjudicated)
    End point description
    Composite of Major BE: Fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; surgical site bleeding that requires second intervention open,arthroscopic,endovascular,or hemarthrosis resulting in prolonged hospitalization, deep wound infection and/or either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.The analysis set: safety set. Here,‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14, Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    2
    0
    2
    1
    1
    1
    5
        Up to Day 52
    0
    2
    0
    2
    2
    1
    1
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects with Major Bleeding Events (CEC-adjudicated)

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    End point title
    Number of Subjects with Major Bleeding Events (CEC-adjudicated)
    End point description
    Number of subjects with major bleeding events (adjudicated by CEC) were reported. Major bleeding was defined as: Fatal bleeding; Bleeding that is symptomatic and occurs in critical area/organ and/or; Extrasurgical site bleeding causing fall in hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; Surgical site bleeding that requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. The safety analysis set was a subset of the ITT analysis set, consisting of all ITT subjects who received at least 1 dose (partial or complete) of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 14; Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    0
    0
    0
    0
    0
    0
    1
        Up to Day 52
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with CRNM Bleeding Events (CEC-adjudicated)

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    End point title
    Number of Subjects with CRNM Bleeding Events (CEC-adjudicated)
    End point description
    Number of subjects with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding events were defined as acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE and meets and is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed, Hematuria, Bruising/ecchymosis, Hemoptysis, Hematoma. The safety analysis set was a subset of the ITT analysis set, consisting of all ITT subjects who received at least 1 dose (partial or complete) of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 14; Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    2
    0
    2
    1
    1
    1
    4
        Up to Day 52
    0
    2
    0
    2
    2
    1
    1
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects with Minimal Bleeding Events (CEC-adjudicated)

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    End point title
    Number of Subjects with Minimal Bleeding Events (CEC-adjudicated)
    End point description
    Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria. The safety analysis set was a subset of the ITT analysis set, consisting of all ITT subjects who received at least 1 dose (partial or complete) of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Day 14; Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    6
    2
    5
    8
    7
    4
    8
        Up to Day 52
    0
    6
    2
    5
    9
    7
    5
    8
    No statistical analyses for this end point

    Secondary: Number of Subjects with Major or CRNM Bleeding Events (CEC-adjudicated)

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    End point title
    Number of Subjects with Major or CRNM Bleeding Events (CEC-adjudicated)
    End point description
    Major Bleeding:Fatal bleeding; That is symptomatic and occurs in critical area/organ and/or;Extrasurgical site bleeding causing fall in Hb level of 20 g/L or more,or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding,and/or;Surgical site bleeding that requires second intervention open,arthroscopic,endovascular,or hemarthrosis resulting in prolonged hospitalization or deep wound infection and/or;Surgical site bleeding that is unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.CRNM bleeding:acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE,still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.The safety analysis set was used.
    End point type
    Secondary
    End point timeframe
    Up to Day 14; Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    296
    Units: subjects
        Up to Day 14
    0
    2
    0
    2
    1
    1
    1
    5
        Up to Day 52
    0
    0
    0
    0
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Major VTE (CEC-adjudicated)

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    End point title
    Number of Subjects with Major VTE (CEC-adjudicated)
    End point description
    Number of subjects with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. mITT at Day 14 included all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    127
    129
    124
    123
    134
    131
    252
    Units: subjects
    0
    2
    1
    1
    0
    2
    0
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects with Major VTE (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Subjects with Major VTE (CEC-adjudicated) Up to Day 52
    End point description
    Number of subjects with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death. The mITT analysis set included all the subjects in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    253
    Units: subjects
    0
    2
    1
    1
    0
    2
    0
    4
    No statistical analyses for this end point

    Secondary: Number of Subjects with Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)

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    End point title
    Number of Subjects with Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
    End point description
    Number of subjects with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. The mITT analysis set at Day 14 includes all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). The subjects whose venography result is not evaluable distal but no proximal clot.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    29
    134
    133
    128
    128
    136
    135
    259
    Units: subjects
        Asymptomatic
    0
    0
    0
    0
    0
    0
    0
    1
        Symptomatic
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Proximal DVT (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Participants with Proximal DVT (CEC-adjudicated) Up to Day 52
    End point description
    Number of subjects with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. The mITT analysis set at Week 6 included all the subjects in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Also included the subjects whose venography result was not evaluable distal but no proximal clot.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    29
    135
    133
    128
    128
    137
    135
    260
    Units: subjects
        Asymptomatic
    0
    0
    0
    0
    0
    0
    0
    1
        Symptomatic
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Distal DVT (CEC-adjudicated)

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    End point title
    Number of Subjects with Distal DVT (CEC-adjudicated)
    End point description
    Number of subjects with distal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. The mITT analysis set at Day 14 included all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here, ‘N’ (number of subjects analyzed) signifies those participants who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    252
    Units: subjects
        Asymptomatic
    7
    27
    26
    13
    8
    10
    10
    50
        Symptomatic
    0
    2
    0
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Distal DVT (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Subjects with Distal DVT (CEC-adjudicated) Up to Day 52
    End point description
    Number of subjects with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic. mITT included all the subjects in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    253
    Units: subjects
        Asymptomatic (Up to Day 52)
    7
    27
    26
    13
    8
    10
    10
    50
        Symptomatic (Up to Day 52)
    0
    2
    2
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects with Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)

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    End point title
    Number of Subjects with Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
    End point description
    Number of subjects with nonfatal PE (adjudicated by CEC) were reported. mITT at Day 14 included all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    127
    129
    124
    123
    134
    131
    252
    Units: subjects
    0
    0
    0
    1
    0
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Nonfatal PE (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Subjects with Nonfatal PE (CEC-adjudicated) Up to Day 52
    End point description
    Number of subjects with nonfatal PE (adjudicated by CEC) were reported. The mITT analysis set included all the participants in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    253
    Units: subjects
    0
    0
    0
    1
    0
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Deaths (CEC-adjudicated)

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    End point title
    Number of Subjects with Deaths (CEC-adjudicated)
    End point description
    Number of subjects with deaths (CEC-adjudicated) were reported. mITT at Day 14 included all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    127
    129
    124
    123
    134
    131
    252
    Units: subjects
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Deaths (CEC-adjudicated) Up to Day 52

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    End point title
    Number of Subjects with Deaths (CEC-adjudicated) Up to Day 52
    End point description
    Number of subjects with deaths (CEC-adjudicated) were reported. mITT at Week 6 included all the subjects in mITT at Day 14 plus the subjects who had symptomatic/asymptomatic VTE events (DVT, non-fatal PE or any death) after day 17 through day 52. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 52
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Number of subjects analysed
    28
    128
    129
    124
    123
    135
    131
    253
    Units: subjects
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Apparent Clearance (CL/F) of JNJ-70033093

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    End point title
    Apparent Clearance (CL/F) of JNJ-70033093
    End point description
    Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure. This outcome measure was planned to be analyzed for overall subjects and not group wise.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Overall
    Number of subjects analysed
    921
    Units: Liter per hour (L/h)
        geometric mean (geometric coefficient of variation)
    8.33 ( 45.8 )
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (V/F) of JNJ-70033093

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    End point title
    Apparent Volume of Distribution (V/F) of JNJ-70033093
    End point description
    V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint. This endpoint was planned to be analyzed for overall subjects and not group wise.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Overall
    Number of subjects analysed
    921
    Units: Liter
        geometric mean (geometric coefficient of variation)
    148 ( 77.6 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographics: Sex on CL/F

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    End point title
    Impact of Selected Demographics: Sex on CL/F
    End point description
    Impact of sex on CL/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Arms are created based on sex (male and female) to report the effect of sex on CL/F. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Female Male
    Number of subjects analysed
    653
    268
    Units: Litres per hour (L/h)
        geometric mean (geometric coefficient of variation)
    7.70 ( 48.4 )
    9.87 ( 36.3 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographic: Age on CL/F

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    End point title
    Impact of Selected Demographic: Age on CL/F
    End point description
    Impact of age CL/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint. Arms are created based on age to report the effect of age on CL/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Age: Less than or Equal to (<=) 68 years Age: Greater than (>) 68 years
    Number of subjects analysed
    464
    457
    Units: L/h
        geometric mean (geometric coefficient of variation)
    9.33 ( 45.5 )
    7.32 ( 41.1 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographic: Weight on CL/F

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    End point title
    Impact of Selected Demographic: Weight on CL/F
    End point description
    Impact of weight) on CL/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoints. Arms are created based on weight to report the effect of weight on CL/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Weight: Less than or Equal to (<=) 82 kilograms (kg) Weight: Greater than (>) 82 kg
    Number of subjects analysed
    486
    435
    Units: L/h
        geometric mean (geometric coefficient of variation)
    7.56 ( 41.2 )
    9.20 ( 46.9 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Laboratory Values: Renal Function on CL/F

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    End point title
    Impact of Selected Laboratory Values: Renal Function on CL/F
    End point description
    Impact of renal function on V/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. The outcome measure was reported based on CRCL. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure. Arms are created based on CRCL to report the effect of renal function on CL/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Creatinine clearance (CRCL): Less than (<) 90 CRCL: Greater than or equal to (>=) 90
    Number of subjects analysed
    442
    447
    Units: L/h
        geometric mean (geometric coefficient of variation)
    7.21 ( 43.4 )
    9.40 ( 43.7 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex

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    End point title
    Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
    End point description
    Impact of sex on V/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure. Arms are created based on sex (male and female) to report the effect of sex on V/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Female Male
    Number of subjects analysed
    653
    268
    Units: Liters
        geometric mean (geometric coefficient of variation)
    140 ( 81.2 )
    166 ( 69.0 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographics : Weight on V/F

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    End point title
    Impact of Selected Demographics : Weight on V/F
    End point description
    Impact of weight on V/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint. Arms are created based on weight to report the effect of weight on CV/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Weight: Less than or Equal to (<=) 82 kilograms (kg) Weight: Greater than (>) 82 kg
    Number of subjects analysed
    486
    435
    Units: Liters
        geometric mean (geometric coefficient of variation)
    127 ( 65.4 )
    171 ( 80.9 )
    No statistical analyses for this end point

    Secondary: Impact of Selected Demographics : Age on V/F

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    End point title
    Impact of Selected Demographics : Age on V/F
    End point description
    Impact of age on V/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this outcome measure. Arms are created based on age to report the effect of sex on V/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Age: Less than or Equal to (<=) 68 years Age: Greater than (>) 68 years
    Number of subjects analysed
    464
    457
    Units: Liters
        geometric mean (geometric coefficient of variation)
    160 ( 83.2 )
    135 ( 66.9 )
    No statistical analyses for this end point

    Secondary: Relationship between JNJ-70033093 Dose Levels with Total VTE

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    End point title
    Relationship between JNJ-70033093 Dose Levels with Total VTE [2]
    End point description
    Relationship between JNJ-70033093 dose levels with total VTE was determined using a multiple comparison procedures and modeling (MCP-Mod) approach. The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here 'number' signifies the estimated response rate.
    End point type
    Secondary
    End point timeframe
    Up to 14 days
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    Units: percentage of subjects
        number (confidence interval 95%)
    0.35 (0.17 to 0.52)
    0.21 (0.16 to 0.25)
    0.20 (0.15 to 0.24)
    0.13 (0.10 to 0.16)
    0.09 (0.07 to 0.12)
    0.09 (0.06 to 0.11)
    0.07 (0.03 to 0.10)
    No statistical analyses for this end point

    Secondary: Impact of Selected Laboratory Values: Renal Function on V/F

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    End point title
    Impact of Selected Laboratory Values: Renal Function on V/F
    End point description
    Impact of renal function on V/F was assessed. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. The outcome measure was reported based on CRCL. Here, ‘N’ (number of subjects analyzed) signifies those subjects who were evaluable for this endpoint. Arms are created based on CRCL to report the effect of renal function on V/F.
    End point type
    Secondary
    End point timeframe
    Up to Day 14
    End point values
    Creatinine clearance (CRCL): Less than (<) 90 CRCL: Greater than or equal to (>=) 90
    Number of subjects analysed
    442
    447
    Units: Liters
        geometric mean (geometric coefficient of variation)
    136 ( 66.3 )
    160 ( 84.5 )
    No statistical analyses for this end point

    Secondary: Relationship Between JNJ-70033093 Dose Levels with Composite of Major or Clinically Relevant Nonmajor Bleeding Events

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    End point title
    Relationship Between JNJ-70033093 Dose Levels with Composite of Major or Clinically Relevant Nonmajor Bleeding Events [3]
    End point description
    Relationship between JNJ-70033093 dose levels with composite of major or clinically relevant nonmajor bleeding events was determined using a MCP-Mod approach. The mITT analysis set at Day 14 included all ITT subjects who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here 'number' signifies the estimated response rate.
    End point type
    Secondary
    End point timeframe
    Up to 14 days
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    Units: percentage of subjects
        number (confidence interval 95%)
    0.02 (0.00 to 0.17)
    0.01 (0.00 to 0.03)
    0.01 (0.00 to 0.04)
    0.01 (0.00 to 0.02)
    0.01 (0.00 to 0.02)
    0.01 (0.00 to 0.02)
    0.01 (0.00 to 0.02)
    No statistical analyses for this end point

    Secondary: Relationship between JNJ-70033093 Dose Levels with Major Bleeding Events

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    End point title
    Relationship between JNJ-70033093 Dose Levels with Major Bleeding Events [4]
    End point description
    Relationship between JNJ-70033093 dose levels with major bleeding events was determined using a MCP-Mod approach. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here "99999" indicates that data was not available as there were no major bleeding events.
    End point type
    Secondary
    End point timeframe
    Up to 14 days
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    Units: unitless
        geometric mean (geometric coefficient of variation)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Relationship between JNJ-70033093 Dose Levels with Clinically Relevant Nonmajor Bleeding Events

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    End point title
    Relationship between JNJ-70033093 Dose Levels with Clinically Relevant Nonmajor Bleeding Events [5]
    End point description
    Relationship between JNJ-70033093 dose levels with clinically relevant nonmajor bleeding events was determined using a MCP-Mod approach. The mITT analysis set at Day 14 included all ITT participants who received at least 1 dose of study drug with an evaluable venography assessment or a confirmed symptomatic VTE event (DVT, non-fatal PE or any death). Here '99999' indicates that data was not available as there were no clinically relevant nonmajor events.
    End point type
    Secondary
    End point timeframe
    Up to 14 days
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID
    Number of subjects analysed
    33
    150
    148
    148
    147
    149
    148
    Units: unitless
        geometric mean (geometric coefficient of variation)
    99999 ( 99999 )
    0.0133 ( 863.1 )
    99999 ( 99999 )
    0.0136 ( 854.4 )
    0.00680 ( 1212.4 )
    0.00671 ( 1220.7 )
    0.00676 ( 0.00676 )
    No statistical analyses for this end point

    Secondary: Relationship between JNJ-70033093 Dose Levels with Minimal Bleeding Events

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    End point title
    Relationship between JNJ-70033093 Dose Levels with Minimal Bleeding Events [6]
    End point description
    Relationship between JNJ-70033093 dose levels with minimal bleeding events was determined using a MCP-Mod approach. The PK analysis set consisted of subjects who received at least 1 dose of milvexian and had at least one valid blood sample drawn for PK analysis. Here "99999" indicates that data was not available as there were no minimal bleeding events.
    End point type
    Secondary
    End point timeframe
    Up to 14 days
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be analyzed for specified arms only.
    End point values
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID
    Number of subjects analysed
    33
    150
    150
    148
    147
    149
    148
    Units: unitless
        geometric mean (geometric coefficient of variation)
    99999 ( 99999 )
    0.0533 ( 422.7 )
    0.0135 ( 857.3 )
    0.0476 ( 448.7 )
    0.0612 ( 392.9 )
    0.0470 ( 451.9 )
    0.0338 ( 536.6 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 6 weeks
    Adverse event reporting additional description
    The safety analysis set is a subset of the intent to treat (ITT) analysis set, consisting of all ITT participants who received at least 1 dose (partial or complete) of study drug.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    JNJ-70033093 25 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 25 mg (1*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg once daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 25 mg + Placebo Twice daily (BID)
    Reporting group description
    Subjects received JNJ-70033093 25 milligram (mg) (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 50 mg BID
    Reporting group description
    Subjects received JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg Once Daily + Placebo
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 100 mg + Placebo BID
    Reporting group description
    Subjects received JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days.

    Reporting group title
    JNJ-70033093 200 mg BID
    Reporting group description
    Subjects received JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days.

    Reporting group title
    Enoxaparin 40 mg Once Daily
    Reporting group description
    Subjects received enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.

    Serious adverse events
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 33 (3.03%)
    2 / 150 (1.33%)
    5 / 148 (3.38%)
    5 / 148 (3.38%)
    2 / 147 (1.36%)
    5 / 149 (3.36%)
    2 / 148 (1.35%)
    11 / 296 (3.72%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    Investigations
    Cardiovascular Evaluation
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    1 / 147 (0.68%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Full Blood Count Decreased
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    1 / 149 (0.67%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoglobin Decreased
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 150 (0.67%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Periprosthetic Fracture
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural Haemorrhage
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 150 (0.67%)
    1 / 148 (0.68%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    2 / 149 (1.34%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femoral Artery Embolism
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial Fibrillation
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    1 / 148 (0.68%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic Stroke
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    1 / 148 (0.68%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    1 / 148 (0.68%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    1 / 147 (0.68%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    1 / 148 (0.68%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    1 / 148 (0.68%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    1 / 149 (0.67%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    1 / 148 (0.68%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Compartment Syndrome
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    1 / 148 (0.68%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Covid-19
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    1 / 149 (0.67%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    1 / 148 (0.68%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    0 / 296 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound Infection
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrolyte Imbalance
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 150 (0.00%)
    0 / 148 (0.00%)
    0 / 148 (0.00%)
    0 / 147 (0.00%)
    0 / 149 (0.00%)
    0 / 148 (0.00%)
    1 / 296 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    JNJ-70033093 25 mg Once Daily + Placebo JNJ-70033093 50 mg once daily + Placebo JNJ-70033093 25 mg + Placebo Twice daily (BID) JNJ-70033093 50 mg BID JNJ-70033093 200 mg Once Daily + Placebo JNJ-70033093 100 mg + Placebo BID JNJ-70033093 200 mg BID Enoxaparin 40 mg Once Daily
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 33 (0.00%)
    6 / 150 (4.00%)
    9 / 148 (6.08%)
    8 / 148 (5.41%)
    3 / 147 (2.04%)
    4 / 149 (2.68%)
    3 / 148 (2.03%)
    17 / 296 (5.74%)
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 33 (0.00%)
    6 / 150 (4.00%)
    9 / 148 (6.08%)
    8 / 148 (5.41%)
    3 / 147 (2.04%)
    4 / 149 (2.68%)
    3 / 148 (2.03%)
    17 / 296 (5.74%)
         occurrences all number
    0
    6
    9
    8
    3
    4
    3
    17

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Sep 2019
    The overall reasons for the amendment was to modify the study design with regards to the planned and optional doses and to remove the option for preoperative dosing and some minor editorial changes.

    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.
    No notable study limitations were identified by the sponsor.
    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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