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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir + Emtricitabine/Tenofovir Alafenamide in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

    Summary
    EudraCT number
    		 2015-003988-10
    Trial protocol
    		 GB   BE   DE   ES   FR   IT  
    Global end of trial date
    05 Jul 2021

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-380-1490
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02607956
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.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
    05 Jul 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 May 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jul 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG) + a FDC containing emtricitabine/tenofovir alafenamide (F/TAF) in HIV-1 infected, antiretroviral treatment-naive adults.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Nov 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 14
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Canada: 22
    Country: Number of subjects enrolled
    Dominican Republic: 45
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Germany: 49
    Country: Number of subjects enrolled
    Italy: 34
    Country: Number of subjects enrolled
    Spain: 34
    Country: Number of subjects enrolled
    United Kingdom: 48
    Country: Number of subjects enrolled
    United States: 391
    Worldwide total number of subjects
    657
    EEA total number of subjects
    137
    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)
    651
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at centers in Australia, Europe, North America, and the Dominican Republic. The first participant was screened on 11 November 2015. The last study visit occurred on 05 July 2021.

    Pre-assignment
    Screening details
    		 742 participants were screened.

    Period 1
    Period 1 title
    Double-Blinded Phase
    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
    		 B/F/TAF
    Arm description
    		 Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) tablets fixed-dose combination (FDC) + dolutegravir (DTG) placebo + F/TAF placebo orally once daily for at least 144 weeks without regard to food.
    Arm type
    		 Experimental

    Investigational medicinal product name
    B/F/TAF
    Investigational medicinal product code
    Other name
    GS-9883/F/TAF
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50/200/25 mg FDC administered once daily

    Investigational medicinal product name
    F/TAF Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered once daily

    Investigational medicinal product name
    DTG Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered once daily

    Arm title
    		 DTG + F/TAF
    Arm description
    		 DTG (50 mg) + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo orally once daily for at least 144 weeks without regard to food.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    DTG
    Investigational medicinal product code
    Other name
    Tivicay®
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg administered once daily

    Investigational medicinal product name
    F/TAF
    Investigational medicinal product code
    Other name
    Descovy®
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/25 mg administered once daily

    Investigational medicinal product name
    B/F/TAF Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered once daily

    Number of subjects in period 1 [1]
    		B/F/TAF DTG + F/TAF
    Started
    320
    325
    Completed
    266
    277
    Not completed
    54
    48
         Protocol violation
    3
    1
         Death
    4
    4
         Investigator's Discretion
    7
    2
         Adverse event
    4
    3
         Non-compliance with study drug
    -
    3
         Lost to follow-up
    19
    16
         Withdrew consent
    17
    19
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Seven participants in B/F/TAF arm and 5 participants in DTG + F/TAF were randomized but were not treated.
    Period 2
    Period 2 title
    Open-Label Extension Phase
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 B/F/TAF to B/F/TAF
    Arm description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    B/F/TAF
    Investigational medicinal product code
    Other name
    GS-9883/F/TAF
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50/200/25 mg FDC administered once daily

    Arm title
    		 DTG+F/TAF to B/F/TAF
    Arm description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    B/F/TAF
    Investigational medicinal product code
    Other name
    GS-9883/F/TAF
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50/200/25 mg FDC administered once daily

    Number of subjects in period 2 [2]
    		B/F/TAF to B/F/TAF DTG+F/TAF to B/F/TAF
    Started
    254
    265
    Completed
    225
    235
    Not completed
    29
    30
         Protocol violation
    -
    2
         Death
    1
    3
         Investigator's Discretion
    2
    2
         Pregnancy
    -
    1
         Non-compliance with study drug
    2
    -
         Lost to follow-up
    14
    6
         Withdrew consent
    10
    16
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 66 participants from B/F/TAF arm did not enter the Open-Label Extension Phase. 60 participants from DTG+F/TAF arm did not enter the Open-Label Extension Phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) tablets fixed-dose combination (FDC) + dolutegravir (DTG) placebo + F/TAF placebo orally once daily for at least 144 weeks without regard to food.

    Reporting group title
    DTG + F/TAF
    Reporting group description
    		 DTG (50 mg) + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo orally once daily for at least 144 weeks without regard to food.

    Reporting group values
    		 B/F/TAF DTG + F/TAF Total
    Number of subjects
    		 320 325 645
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 37 ± 12.3 37 ± 11.6 -
    Gender categorical
    Units: Subjects
        Female
    		 40 37 77
        Male
    		 280 288 568
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 7 10 17
        Black
    		 97 100 197
        Native Hawaiian or Pacific Islander
    		 1 0 1
        White
    		 183 195 378
        Other
    		 31 19 50
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 83 81 164
        Not Hispanic or Latino
    		 237 244 481
    HIV-1 RNA Categories
    Units: Subjects
        ≤ 100,000 copies/mL
    		 254 271 525
        > 100,000 ≤ 400,000 copies/mL
    		 54 41 95
        > 400,000 copies/mL
    		 12 13 25
    CD4 Cell Count Categories
    Units: Subjects
        < 50 cells/μL
    		 15 13 28
        ≥ 50 to < 200 cells/μL
    		 29 21 50
        ≥ 200 to < 350 cells/μL
    		 67 77 144
        ≥ 350 to < 500 cells/μL
    		 91 94 185
        ≥ 500 cells/ μL
    		 118 120 238
    HIV-1 RNA
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    		 4.39 ± 0.730 4.42 ± 0.669 -
    CD4 Cell Count
    Units: Cells/μL
        arithmetic mean (standard deviation)
    		 457 ± 255.3 454 ± 231.5 -

    End points

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    End points reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) tablets fixed-dose combination (FDC) + dolutegravir (DTG) placebo + F/TAF placebo orally once daily for at least 144 weeks without regard to food.

    Reporting group title
    DTG + F/TAF
    Reporting group description
    		 DTG (50 mg) + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo orally once daily for at least 144 weeks without regard to food.
    Reporting group title
    B/F/TAF to B/F/TAF
    Reporting group description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.

    Reporting group title
    DTG+F/TAF to B/F/TAF
    Reporting group description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive open-label (OL) B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.

    Subject analysis set title
    All B/F/TAF
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Blinded Phase: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) tablets fixed-dose combination (FDC) + dolutegravir (DTG) placebo + F/TAF placebo orally once daily for at least 144 weeks without regard to food. Open-Label Extension Phase: After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive OL B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.

    Primary: Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    89.4
    92.9
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Differences in percentages of participants between groups and their 95.002% CIs were calculated based on Mantel-Haenszel (MH) proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 1
    Notes
    [1] - A sample of approximately 600 participants randomized 1:1 achieves at least 95% power using a non-inferiority margin of 12% assuming a response rate in both groups of 91% (Reference Genvoya studies) and a one-sided alpha level of 0.025.
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.12 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [2] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    84.1
    86.5
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Differences in percentages of participants between groups and their 95% CIs were calculated based on MH proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -2.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 3.2
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.41 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [3] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 144 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    81.9
    84.0
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Differences in percentages of participants between groups and their 95% CIs were calculated based on MH proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.8
         upper limit
    		 3.9
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.52 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [4] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    82.2
    87.1
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    The differences in percentages of participants between treatment groups and their 95% CIs were calculated based on the MH proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.4
         upper limit
    		 1.5
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.16 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [5] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    77.5
    80.3
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    The differences in percentages of participants between treatment groups and their 95% CIs were calculated based on the MH proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.8
         upper limit
    		 3.8
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.44 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [6] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Week 144 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    320
    325
    Units: percentage of participants
        number (not applicable)
    77.5
    79.1
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    The differences in percentages of participants between treatment groups and their 95% CIs were calculated based on the MH proportions adjusted by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 5.3
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    645
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.74 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval
    Notes
    [7] - p-value was calculated from CMH test stratified by baseline HIV-1 RNA stratum (≤ 100,000 vs. > 100,000 copies/mL) and region stratum (US vs. Ex-US).

    Secondary: Change From Baseline in log10 HIV-1 RNA at Week 48

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    End point title
    		 Change From Baseline in log10 HIV-1 RNA at Week 48
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    294
    308
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    -3.07 ± 0.719
    -3.12 ± 0.672
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in least-squares mean (LSM), and its 95% confidence interval (CI) were adjusted by baseline HIV-1 RNA stratum and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    602
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.081 [8]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.17
    Notes
    [8] - p-value was adjusted by baseline HIV-1 RNA stratum and region stratum.

    Secondary: Change From Baseline in log10 HIV-1 RNA at Week 96

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    End point title
    		 Change From Baseline in log10 HIV-1 RNA at Week 96
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 96
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    276
    291
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    -3.08 ± 0.703
    -3.10 ± 0.713
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in LSM, and its 95% CI were adjusted by baseline HIV-1 RNA stratum and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.18 [9]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.15
    Notes
    [9] - p-value was adjusted by baseline HIV-1 RNA stratum and region stratum.

    Secondary: Change From Baseline in log10 HIV-1 RNA at Week 144

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    End point title
    		 Change From Baseline in log10 HIV-1 RNA at Week 144
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 144
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    270
    280
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    -3.06 ± 0.731
    -3.11 ± 0.672
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in LSM, and its 95% CI were adjusted by baseline HIV-1 RNA stratum and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    550
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.054 [10]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.18
    Notes
    [10] - p-value was adjusted by baseline HIV-1 RNA stratum and region stratum.

    Secondary: Change From Baseline in CD4+ Cell Count at Week 48

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    End point title
    		 Change From Baseline in CD4+ Cell Count at Week 48
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    290
    304
    Units: cells/μL
        arithmetic mean (standard deviation)
    180 ± 166.2
    201 ± 165.9
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in LSM, and its 95% CI were adjusted by the baseline HIV-1 RNA and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    594
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.096 [11]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -49
         upper limit
    		 4
    Notes
    [11] - P-value was adjusted by the baseline HIV-1 RNA and region stratum.

    Secondary: Change From Baseline in CD4+ Cell Count at Week 96

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    End point title
    		 Change From Baseline in CD4+ Cell Count at Week 96
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 96
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    269
    285
    Units: cells/μL
        arithmetic mean (standard deviation)
    237 ± 204.2
    281 ± 209.3
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in LSM, and its 95% CI were adjusted by the baseline HIV-1 RNA and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    554
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.008 [12]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -81
         upper limit
    		 -12
    Notes
    [12] - P-value was adjusted by the baseline HIV-1 RNA and region stratum.

    Secondary: Change From Baseline in CD4+ Cell Count at Week 144

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    End point title
    		 Change From Baseline in CD4+ Cell Count at Week 144
    End point description
    Participants in the Full Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 144
    End point values
    		 B/F/TAF DTG + F/TAF
    Number of subjects analysed
    262
    277
    Units: cells/μL
        arithmetic mean (standard deviation)
    278 ± 236.6
    289 ± 218.5
    Statistical analysis title
    		 B/F/TAF, DTG + F/TAF
    Statistical analysis description
    Difference in LSM, and its 95% CI were adjusted by baseline HIV-1 RNA stratum and region stratum.
    Comparison groups
    B/F/TAF v DTG + F/TAF
    Number of subjects included in analysis
    539
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.48 [13]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -52
         upper limit
    		 25
    Notes
    [13] - p-value was adjusted by baseline HIV-1 RNA stratum and region stratum.

    Secondary: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm

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    End point title
    		 Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with nonmissing HIV-1 RNA value at that visit. Participants in All B/F/TAF Analysis Set (who were randomized into the randomized phase of the study and received at least 1 dose of the B/F/TAF in the randomized phase or at least 1 dose of the B/F/TAF in the open label extension phase) with available data were analyzed. For the B/F/TAF group, Week 48 open-label time point refers to Week 192; for Missing = Excluded analysis, it included the available participants at that time point from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 48
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    225
    243
    Units: percentage of participants
        number (confidence interval 95%)
    99.6 (97.5 to 100)
    99.2 (97.1 to 99.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure algorithm

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    End point title
    		 Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure algorithm
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was treated as HIV-1 RNA ≥ 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set. Participants in the All B/F/TAF Analysis Set were analyzed. For the B/F/TAF group, Week 48 open-label time point refers to Week 192; for Missing = Failure analysis, it included all participants from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 48
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    265
    320
    Units: percentage of participants
        number (confidence interval 95%)
    84.5 (79.6 to 88.7)
    75.3 (70.2 to 79.9)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm

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    End point title
    		 Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Excluded for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). The denominator for percentages at a visit was the number of participants in the all B/F/TAF analysis set with nonmissing HIV-1 RNA value at that visit. Participants in All B/F/TAF Analysis Set with available data were analyzed. For the B/F/TAF group, Week 96 open-label time point refers to Week 240; for Missing = Excluded analysis, it included the available participants at that time point from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 96
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    234
    219
    Units: percentage of participants
        number (confidence interval 95%)
    99.1 (96.9 to 99.9)
    99.5 (97.5 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure algorithm

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    End point title
    		 Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure algorithm
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL was analyzed using Missing = Failure for imputing missing HIV-1 RNA values using the All B/F/TAF Analysis Set for the all B/F/TAF analysis. All missing data was treated as HIV-1 RNA ≥ 50 copies/mL. The denominator for percentages was the number of participants in all B/F/TAF analysis set. Participants in the All B/F/TAF Analysis Set were analyzed. For the B/F/TAF group, Week 96 open-label time point refers to Week 240; for Missing = Failure analysis, it included all participants from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 96
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    265
    320
    Units: percentage of participants
        number (confidence interval 95%)
    87.5 (83.0 to 91.3)
    68.1 (62.7 to 73.2)
    No statistical analyses for this end point

    Secondary: Change From Baseline in CD4+ Cell Count at Week 48 Open-Label

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    End point title
    		 Change From Baseline in CD4+ Cell Count at Week 48 Open-Label
    End point description
    Participants in the All B/F/TAF Analysis Set with available data were analyzed. For the B/F/TAF group, Week 48 open-label time point refers to Week 192; for Change from Baseline in CD4 Cell Count analysis, it included the available participants at that time point from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 48
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    223
    241
    Units: cells/μL
        arithmetic mean (standard deviation)
    9 ± 198.0
    304 ± 249.2
    No statistical analyses for this end point

    Secondary: Change From Baseline in CD4+ Cell Count at Week 96 Open-Label

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    End point title
    		 Change From Baseline in CD4+ Cell Count at Week 96 Open-Label
    End point description
    Participants in the All B/F/TAF Analysis Set with available data were analyzed. For the B/F/TAF group, Week 96 open-label time point refers to Week 240; for Change from Baseline in CD4 Cell Count analysis, it included the available participants at that time point from the Randomized Phase.
    End point type
    Secondary
    End point timeframe
    Baseline, open-label Week 96
    End point values
    		 DTG+F/TAF to B/F/TAF All B/F/TAF
    Number of subjects analysed
    210
    225
    Units: cells/µL
        arithmetic mean (standard deviation)
    -10 ± 181.1
    336 ± 235.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events: First dose date up to last dose date (maximum: 281.4 weeks) plus 30 days All-Cause Mortality: Randomization date through last visit/follow up date (maximum: 287.1 weeks)
    Adverse event reporting additional description
    Adverse Events: Safety Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug. All-Cause Mortality: All Randomized Analysis Set included all participants randomized into the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 B/F/TAF (50/200/25 mg) FDC + DTG placebo + F/TAF placebo orally once daily for at least 144 weeks, without regard to food.

    Reporting group title
    DTG + F/TAF
    Reporting group description
    		 DTG (50 mg) + F/TAF (200/25 mg) FDC tablet + B/F/TAF placebo orally once daily for at least 144 weeks, without regard to food.

    Reporting group title
    B/F/TAF to B/F/TAF
    Reporting group description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive OL B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.

    Reporting group title
    DTG+F/TAF to B/F/TAF
    Reporting group description
    		 After Week 144, participants continued to take their blinded study drug and attended visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants were given the option to receive OL B/F/TAF for 96 weeks. After the Week 96 OL Visit, participants in a country where B/F/TAF was not commercially available were given the option to continue OL B/F/TAF until the product became accessible through an access program or until Gilead elected to discontinue the study in that country, whichever occured first.

    Serious adverse events
    		 B/F/TAF DTG + F/TAF B/F/TAF to B/F/TAF DTG+F/TAF to B/F/TAF
    Total subjects affected by serious adverse events
         subjects affected / exposed
    64 / 320 (20.00%)
    46 / 325 (14.15%)
    20 / 254 (7.87%)
    32 / 265 (12.08%)
         number of deaths (all causes)
    4
    4
    1
    3
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Anogenital warts
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    B-cell lymphoma
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Central nervous system lymphoma
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleomorphic adenoma
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 320 (0.63%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive emergency
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Oesophagogastric fundoplasty
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion incomplete
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 320 (0.00%)
    2 / 325 (0.62%)
    1 / 254 (0.39%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    0 / 2
    Chest pain
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 320 (0.31%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillar disorder
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    2 / 320 (0.63%)
    1 / 325 (0.31%)
    1 / 254 (0.39%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug abuse
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute psychosis
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seasonal affective disorder
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance use disorder
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance-induced psychotic disorder
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Transaminases increased
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Road traffic accident
         subjects affected / exposed
    0 / 320 (0.00%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heat stroke
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal injury
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive heart disease
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 320 (0.00%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bell's palsy
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cubital tunnel syndrome
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral artery stenosis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iridocyclitis
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 320 (0.00%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fissure
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal ulcer
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Volvulus
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 320 (0.94%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid mass
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    3 / 320 (0.94%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthralgia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip deformity
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc displacement
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle tightness
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    6 / 320 (1.88%)
    1 / 325 (0.31%)
    1 / 254 (0.39%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 320 (0.31%)
    4 / 325 (1.23%)
    2 / 254 (0.79%)
    2 / 265 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    3 / 320 (0.94%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 320 (0.31%)
    2 / 325 (0.62%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    3 / 320 (0.94%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    2 / 254 (0.79%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shigella infection
         subjects affected / exposed
    2 / 320 (0.63%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess neck
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amoebic dysentery
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal infection
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blister infected
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye infection syphilitic
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis shigella
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    1 / 254 (0.39%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    1 / 265 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 320 (0.00%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 320 (0.31%)
    1 / 325 (0.31%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fluid overload
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolic acidosis
         subjects affected / exposed
    1 / 320 (0.31%)
    0 / 325 (0.00%)
    0 / 254 (0.00%)
    0 / 265 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 B/F/TAF DTG + F/TAF B/F/TAF to B/F/TAF DTG+F/TAF to B/F/TAF
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    250 / 320 (78.13%)
    262 / 325 (80.62%)
    165 / 254 (64.96%)
    163 / 265 (61.51%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts
         subjects affected / exposed
    18 / 320 (5.63%)
    11 / 325 (3.38%)
    1 / 254 (0.39%)
    6 / 265 (2.26%)
         occurrences all number
    20
    12
    1
    6
    Vascular disorders
    Hypertension
         subjects affected / exposed
    19 / 320 (5.94%)
    22 / 325 (6.77%)
    4 / 254 (1.57%)
    8 / 265 (3.02%)
         occurrences all number
    19
    23
    4
    9
    Nervous system disorders
    Headache
         subjects affected / exposed
    57 / 320 (17.81%)
    59 / 325 (18.15%)
    16 / 254 (6.30%)
    19 / 265 (7.17%)
         occurrences all number
    72
    74
    18
    23
    Dizziness
         subjects affected / exposed
    17 / 320 (5.31%)
    20 / 325 (6.15%)
    7 / 254 (2.76%)
    5 / 265 (1.89%)
         occurrences all number
    20
    24
    7
    6
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    24 / 320 (7.50%)
    23 / 325 (7.08%)
    5 / 254 (1.97%)
    3 / 265 (1.13%)
         occurrences all number
    29
    24
    6
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    29 / 320 (9.06%)
    37 / 325 (11.38%)
    4 / 254 (1.57%)
    13 / 265 (4.91%)
         occurrences all number
    30
    38
    5
    13
    Pyrexia
         subjects affected / exposed
    21 / 320 (6.56%)
    31 / 325 (9.54%)
    6 / 254 (2.36%)
    9 / 265 (3.40%)
         occurrences all number
    24
    35
    8
    13
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    66 / 320 (20.63%)
    54 / 325 (16.62%)
    15 / 254 (5.91%)
    15 / 265 (5.66%)
         occurrences all number
    86
    69
    16
    17
    Nausea
         subjects affected / exposed
    31 / 320 (9.69%)
    43 / 325 (13.23%)
    8 / 254 (3.15%)
    11 / 265 (4.15%)
         occurrences all number
    35
    52
    9
    13
    Abdominal pain
         subjects affected / exposed
    23 / 320 (7.19%)
    23 / 325 (7.08%)
    4 / 254 (1.57%)
    7 / 265 (2.64%)
         occurrences all number
    25
    24
    5
    8
    Vomiting
         subjects affected / exposed
    23 / 320 (7.19%)
    22 / 325 (6.77%)
    5 / 254 (1.97%)
    5 / 265 (1.89%)
         occurrences all number
    26
    27
    5
    7
    Dyspepsia
         subjects affected / exposed
    21 / 320 (6.56%)
    14 / 325 (4.31%)
    2 / 254 (0.79%)
    5 / 265 (1.89%)
         occurrences all number
    27
    14
    2
    5
    Constipation
         subjects affected / exposed
    16 / 320 (5.00%)
    15 / 325 (4.62%)
    4 / 254 (1.57%)
    3 / 265 (1.13%)
         occurrences all number
    18
    16
    4
    3
    Abdominal pain upper
         subjects affected / exposed
    16 / 320 (5.00%)
    13 / 325 (4.00%)
    5 / 254 (1.97%)
    2 / 265 (0.75%)
         occurrences all number
    19
    14
    5
    2
    Toothache
         subjects affected / exposed
    16 / 320 (5.00%)
    9 / 325 (2.77%)
    5 / 254 (1.97%)
    3 / 265 (1.13%)
         occurrences all number
    18
    10
    5
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    28 / 320 (8.75%)
    30 / 325 (9.23%)
    16 / 254 (6.30%)
    9 / 265 (3.40%)
         occurrences all number
    32
    39
    17
    9
    Oropharyngeal pain
         subjects affected / exposed
    20 / 320 (6.25%)
    19 / 325 (5.85%)
    8 / 254 (3.15%)
    7 / 265 (2.64%)
         occurrences all number
    24
    23
    9
    7
    Nasal congestion
         subjects affected / exposed
    17 / 320 (5.31%)
    11 / 325 (3.38%)
    4 / 254 (1.57%)
    1 / 265 (0.38%)
         occurrences all number
    19
    11
    4
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    15 / 320 (4.69%)
    27 / 325 (8.31%)
    7 / 254 (2.76%)
    11 / 265 (4.15%)
         occurrences all number
    19
    30
    7
    12
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    29 / 320 (9.06%)
    25 / 325 (7.69%)
    8 / 254 (3.15%)
    14 / 265 (5.28%)
         occurrences all number
    33
    26
    8
    15
    Depression
         subjects affected / exposed
    21 / 320 (6.56%)
    26 / 325 (8.00%)
    9 / 254 (3.54%)
    9 / 265 (3.40%)
         occurrences all number
    21
    27
    9
    9
    Anxiety
         subjects affected / exposed
    16 / 320 (5.00%)
    26 / 325 (8.00%)
    9 / 254 (3.54%)
    9 / 265 (3.40%)
         occurrences all number
    17
    26
    9
    9
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    30 / 320 (9.38%)
    44 / 325 (13.54%)
    18 / 254 (7.09%)
    12 / 265 (4.53%)
         occurrences all number
    33
    54
    20
    13
    Arthralgia
         subjects affected / exposed
    36 / 320 (11.25%)
    33 / 325 (10.15%)
    16 / 254 (6.30%)
    17 / 265 (6.42%)
         occurrences all number
    41
    37
    17
    18
    Pain in extremity
         subjects affected / exposed
    27 / 320 (8.44%)
    11 / 325 (3.38%)
    8 / 254 (3.15%)
    13 / 265 (4.91%)
         occurrences all number
    29
    12
    9
    14
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    51 / 320 (15.94%)
    62 / 325 (19.08%)
    19 / 254 (7.48%)
    22 / 265 (8.30%)
         occurrences all number
    94
    108
    20
    24
    Upper respiratory tract infection
         subjects affected / exposed
    44 / 320 (13.75%)
    54 / 325 (16.62%)
    15 / 254 (5.91%)
    17 / 265 (6.42%)
         occurrences all number
    61
    80
    16
    20
    Syphilis
         subjects affected / exposed
    34 / 320 (10.63%)
    33 / 325 (10.15%)
    20 / 254 (7.87%)
    17 / 265 (6.42%)
         occurrences all number
    39
    39
    22
    19
    Influenza
         subjects affected / exposed
    27 / 320 (8.44%)
    24 / 325 (7.38%)
    15 / 254 (5.91%)
    11 / 265 (4.15%)
         occurrences all number
    43
    32
    17
    14
    Bronchitis
         subjects affected / exposed
    15 / 320 (4.69%)
    28 / 325 (8.62%)
    10 / 254 (3.94%)
    7 / 265 (2.64%)
         occurrences all number
    15
    31
    12
    7
    Covid-19
         subjects affected / exposed
    0 / 320 (0.00%)
    0 / 325 (0.00%)
    26 / 254 (10.24%)
    31 / 265 (11.70%)
         occurrences all number
    0
    0
    26
    32
    Anal chlamydia infection
         subjects affected / exposed
    18 / 320 (5.63%)
    18 / 325 (5.54%)
    11 / 254 (4.33%)
    8 / 265 (3.02%)
         occurrences all number
    22
    20
    14
    9
    Chlamydial infection
         subjects affected / exposed
    14 / 320 (4.38%)
    26 / 325 (8.00%)
    5 / 254 (1.97%)
    6 / 265 (2.26%)
         occurrences all number
    14
    33
    5
    6
    Sinusitis
         subjects affected / exposed
    25 / 320 (7.81%)
    10 / 325 (3.08%)
    10 / 254 (3.94%)
    5 / 265 (1.89%)
         occurrences all number
    34
    11
    12
    5
    Gonorrhoea
         subjects affected / exposed
    18 / 320 (5.63%)
    24 / 325 (7.38%)
    2 / 254 (0.79%)
    4 / 265 (1.51%)
         occurrences all number
    19
    35
    3
    4
    Gastroenteritis
         subjects affected / exposed
    15 / 320 (4.69%)
    18 / 325 (5.54%)
    5 / 254 (1.97%)
    8 / 265 (3.02%)
         occurrences all number
    17
    29
    6
    8
    Urinary tract infection
         subjects affected / exposed
    19 / 320 (5.94%)
    14 / 325 (4.31%)
    3 / 254 (1.18%)
    9 / 265 (3.40%)
         occurrences all number
    23
    17
    4
    12
    Proctitis gonococcal
         subjects affected / exposed
    12 / 320 (3.75%)
    17 / 325 (5.23%)
    3 / 254 (1.18%)
    8 / 265 (3.02%)
         occurrences all number
    15
    20
    3
    9
    Pharyngitis
         subjects affected / exposed
    22 / 320 (6.88%)
    11 / 325 (3.38%)
    4 / 254 (1.57%)
    1 / 265 (0.38%)
         occurrences all number
    23
    11
    5
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Feb 2016
    • Clarified criteria for discontinuation of study treatment and for management of laboratory toxicity • Included guidance for management of potential hepatobiliary toxicity
    19 Oct 2016
    • Extended duration of blinded phase from 96 weeks of treatment to 144 weeks of treatment • Revised secondary objectives and end point to include Week 144 • Added OL rollover extension and treatment assessments for participants who receive OL BVY • Revised language to the risk/benefit assessment for the study • Revised prior and concomitant medications • Added hepatitis B virus (HBV) and hepatitis C virus (HCV) serology testing at Week 48 and every 48 weeks after Week 48 • Revised Gilead reporting requirements to clarify that in addition to using the reference safety information in the investigator’s brochure and relevant local label as applicable, Gilead may also use the European Union (EU) summary of product characteristics for the assessment of expectedness of serious adverse events (SAEs) • Revised the definition of special situations • Added peripheral blood mononuclear cell (PBMC) collection at Week 132 in the PBMC substudy
    06 May 2019
    • Extended the duration of the OL Extension phase of the study from 48 to 96 weeks to allow collection of longer term safety and efficacy data • Revised the secondary objectives and end point • Revised the duration of treatment • Revised the procedures for breaking treatment codes • Added prior and concomitant medications table for BVY OL Extension • Revised End of Blinded Treatment Visit • Revised treatment assessments (OL Rollover Extension) • Revised participant with HIV-1 ribonucleic acid (RNA) ≥ 50 copies/mL instructions to include Week 96 OL • Revised instructions for reporting special situation • Added a section for All BVY Analysis Set and an efficacy analysis for all BVY analysis • Revised safety analysis • Revised Analysis Schedule • Revised Appendix 3 to include OL visits through 96 Weeks

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/28867499
    http://www.ncbi.nlm.nih.gov/pubmed/29956087
    http://www.ncbi.nlm.nih.gov/pubmed/30803969
    http://www.ncbi.nlm.nih.gov/pubmed/31068270
    http://www.ncbi.nlm.nih.gov/pubmed/31068272
    http://www.ncbi.nlm.nih.gov/pubmed/30932951
    http://www.ncbi.nlm.nih.gov/pubmed/32504574
    http://www.ncbi.nlm.nih.gov/pubmed/33880558
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