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    Clinical Trial Results:
    A Phase 3b, Randomized, Double-Blind, Switch Study to Evaluate F/TAF in HIV-1 Infected Subjects who are Virologically Suppressed on Regimens containing ABC/3TC

    Summary
    EudraCT number
    		 2015-000871-28
    Trial protocol
    		 SE   BE   DE   DK   IE   ES   IT  
    Global end of trial date
    13 Mar 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Oct 2019
    First version publication date
    30 Oct 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-311-1717
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02469246
    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
    13 Mar 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Dec 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Mar 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study were to evaluate the efficacy, safety, and tolerability of switching abacavir/lamivudine (ABC/3TC) fixed-dose combination (FDC) tablets to emtricitabine/tenofovir alafenamide (F/TAF) FDC tablets versus maintaining ABC/3TC in human immunodeficiency virus type 1 (HIV-1) infected adults who are virologically suppressed on regimens containing ABC/3TC.
    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
    		 Participants received an allowed 3rd antiretroviral (ARV) agent of the participant's pre-existing regimen (boosted with F/TAF 200/10 mg FDC or unboosted with F/TAF 200/25 mg FDC). An allowed 3rd ARV agent of the participant's pre-existing regimen may have included one of the following boosted ARV agents: ritonavir boosted lopinavir (LPV/r), atazanavir (ATV) + ritonavir (RTV), ATV + cobicistat (COBI) or ATV/COBI FDC, darunavir (DRV) + RTV, DRV+COBI or DRV/COBI FDC; or, one of the following unboosted ARV agents: efavirenz (EFV), rilpivirine (RPV), raltegravir (RAL), dolutegravir (DTG), maraviroc (MVC), or nevirapine (NVP).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jun 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
    Spain: 71
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    United Kingdom: 112
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Denmark: 7
    Country: Number of subjects enrolled
    France: 36
    Country: Number of subjects enrolled
    Germany: 39
    Country: Number of subjects enrolled
    Ireland: 18
    Country: Number of subjects enrolled
    United States: 199
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    Puerto Rico: 8
    Country: Number of subjects enrolled
    Italy: 43
    Worldwide total number of subjects
    567
    EEA total number of subjects
    343
    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)
    526
    From 65 to 84 years
    41
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at study sites in North America and Europe. The first participant was screened on 29 June 2015. The last study visit occurred on 13 March 2019.

    Pre-assignment
    Screening details
    		 626 participants were screened.

    Period 1
    Period 1 title
    Double-Blind 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
    		 F/TAF
    Arm description
    		 Double-Blind Phase: F/TAF (200/10 mg) FDC tablet (with boosted 3rd ARV agent) or F/TAF (200/25 mg) FDC tablet (with unboosted 3rd ARV agent) + ABC/3TC placebo tablet once daily for 96 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Emtricitabine/tenofovir alafenamide
    Investigational medicinal product code
    Other name
    F/TAF; Descovy®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/10 mg FDC tablet (with boosted 3rd ARV agent) or 200/25 mg FDC tablet (with unboosted 3rd ARV agent) administered orally once daily

    Investigational medicinal product name
    ABC/3TC Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet administered orally once daily

    Arm title
    		 ABC/3TC
    Arm description
    		 Double-Blind Phase: ABC/3TC (600/300 mg) FDC tablet + F/TAF placebo tablet once daily + allowed 3rd ARV agent for 96 weeks.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Abacavir/lamivudine
    Investigational medicinal product code
    Other name
    ABC/3TC
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600/300 mg FDC tablet administered orally once daily

    Investigational medicinal product name
    F/TAF Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tablet administered orally once daily

    Number of subjects in period 1 [1]
    		F/TAF ABC/3TC
    Started
    280
    276
    Completed
    218
    226
    Not completed
    62
    50
         Withdrew Consent
    25
    25
         Adverse Event
    12
    9
         Non-Compliance with Study Drug
    3
    1
         Death
    2
    -
         Investigator's Discretion
    8
    8
         Protocol Violation
    1
    1
         Lost to follow-up
    9
    5
         Lack of efficacy
    2
    1
    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: 11 participants (5 F/TAF; 6 ABC/3TC) who were randomized but not treated are not included in the subject disposition table.
    Period 2
    Period 2 title
    Open-Label Extension (OLE)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 F/TAF to Open-Label F/TAF
    Arm description
    		 Open-Label Extension: After the unblinding visit, in countries where F/TAF FDC was not commercially available, participants (except in certain countries) were given the option to receive the open-label F/TAF FDC and attend study visits every 12 weeks until it became commercially available, or until Gilead terminated the study in that country.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Emtricitabine/tenofovir alafenamide
    Investigational medicinal product code
    Other name
    F/TAF; Descovy®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/10 mg FDC tablet (with boosted 3rd ARV agent) or 200/25 mg FDC tablet (with unboosted 3rd ARV agent) administered orally once daily

    Arm title
    		 ABC/3TC to Open-Label F/TAF
    Arm description
    		 Open-Label Extension: After the unblinding visit, in countries where F/TAF FDC was not commercially available, participants (except in certain countries) were given the option to receive the open-label F/TAF FDC and attend study visits every 12 weeks until it became commercially available, or until Gilead terminated the study in that country.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Emtricitabine/tenofovir alafenamide
    Investigational medicinal product code
    Other name
    F/TAF; Descovy®
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/10 mg FDC tablet (with boosted 3rd ARV agent) or 200/25 mg FDC tablet (with unboosted 3rd ARV agent) administered orally once daily

    Number of subjects in period 2 [2]
    		F/TAF to Open-Label F/TAF ABC/3TC to Open-Label F/TAF
    Started
    6
    5
    Completed
    6
    5
    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: Only participants in countries where F/TAF was not commercially available were eligible for the OLE.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    F/TAF
    Reporting group description
    		 Double-Blind Phase: F/TAF (200/10 mg) FDC tablet (with boosted 3rd ARV agent) or F/TAF (200/25 mg) FDC tablet (with unboosted 3rd ARV agent) + ABC/3TC placebo tablet once daily for 96 weeks

    Reporting group title
    ABC/3TC
    Reporting group description
    		 Double-Blind Phase: ABC/3TC (600/300 mg) FDC tablet + F/TAF placebo tablet once daily + allowed 3rd ARV agent for 96 weeks.

    Reporting group values
    		 F/TAF ABC/3TC Total
    Number of subjects
    		 280 276 556
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 51 ± 9.4 51 ± 9.3 -
    Gender categorical
    Units: Subjects
        Female
    		 40 61 101
        Male
    		 240 215 455
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 5 5 10
        Black
    		 64 66 130
        White
    		 205 199 404
        Other
    		 5 6 11
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 16 19 35
        Not Hispanic or Latino
    		 264 257 521
    HIV-1 RNA Category
    Units: Subjects
        < 50 copies/mL
    		 278 273 551
        ≥ 50 copies/mL
    		 2 3 5
    CD4 Cell Count Category
    Units: Subjects
        < 50 cells/μL
    		 0 1 1
        ≥ 50 to < 200 cells/μL
    		 0 0 0
        ≥ 200 to < 350 cells/μL
    		 20 16 36
        ≥ 350 to < 500 cells/μL
    		 56 38 94
        ≥ 500 cells/μL
    		 204 221 425
    HIV Disease Status
    Units: Subjects
        Asymptomatic
    		 201 201 402
        Symptomatic HIV Infection
    		 31 24 55
        AIDS
    		 47 50 97
        Unknown
    		 1 1 2
    CD4 Cell Count
    Units: cells/μL
        arithmetic mean (standard deviation)
    		 703 ± 298.7 727 ± 275.2 -

    End points

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    End points reporting groups
    Reporting group title
    F/TAF
    Reporting group description
    		 Double-Blind Phase: F/TAF (200/10 mg) FDC tablet (with boosted 3rd ARV agent) or F/TAF (200/25 mg) FDC tablet (with unboosted 3rd ARV agent) + ABC/3TC placebo tablet once daily for 96 weeks

    Reporting group title
    ABC/3TC
    Reporting group description
    		 Double-Blind Phase: ABC/3TC (600/300 mg) FDC tablet + F/TAF placebo tablet once daily + allowed 3rd ARV agent for 96 weeks.
    Reporting group title
    F/TAF to Open-Label F/TAF
    Reporting group description
    		 Open-Label Extension: After the unblinding visit, in countries where F/TAF FDC was not commercially available, participants (except in certain countries) were given the option to receive the open-label F/TAF FDC and attend study visits every 12 weeks until it became commercially available, or until Gilead terminated the study in that country.

    Reporting group title
    ABC/3TC to Open-Label F/TAF
    Reporting group description
    		 Open-Label Extension: After the unblinding visit, in countries where F/TAF FDC was not commercially available, participants (except in certain countries) were given the option to receive the open-label F/TAF FDC and attend study visits every 12 weeks until it became commercially available, or until Gilead terminated the study in that country.

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

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the 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. The Full Analysis Set included all participants who were randomized into the study and received at least 1 dose of study drug. Participants were grouped according to the treatment to which they were randomized.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    88.6
    92.4
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of the primary efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95.002% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests. Note that the confidence interval for the difference in percentages was actually 95.002%, but the EudraCT system automatically rounds the value to 95%.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 = 0.15
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 1.1
    Notes
    [1] - Non-inferiority was assessed using a 2-sided exact 95% confidence interval (CI) approach, with a non-inferiority margin of 10%.

    Secondary: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants with 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. Participants in the Full Analysis Set were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    1.8
    0.7
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95.002% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests. Note that the confidence interval for the difference in percentages was actually 95.002%, but the EudraCT system automatically rounds the value to 95%.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 = 0.45
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 3.5
    Notes
    [2] - Non-inferiority was assessed using a 2-sided exact 95% CI approach, with a non-inferiority margin of 4%.

    Secondary: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm

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    End point title
    		 Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Determined by the FDA-Defined Snapshot Algorithm
    End point description
    The percentage of participants with 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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    2.5
    1.1
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    P-value
    		 = 0.34
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1
         upper limit
    		 4.2
    Notes
    [3] - Non-inferiority was assessed using a 2-sided exact 95% CI approach, with a non-inferiority margin of 4%.

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

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Determined by the 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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    82.1
    88.4
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of this efficacy endpoint was to assess the non-inferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    P-value
    		 = 0.042
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    -6.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.3
         upper limit
    		 -0.3
    Notes
    [4] - Non-inferiority was assessed using a 2-sided exact 95% CI approach, with a non-inferiority margin of 4%.

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

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 as Determined by the 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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    85.7
    87.3
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of this efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    P-value
    		 = 0.62
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.4
         upper limit
    		 4.2
    Notes
    [5] - Non-inferiority was assessed using a 2-sided exact 95% CI approach, with a non-inferiority margin of 10%.

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

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 96 as Determined by the 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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    280
    276
    Units: percentage of participants
        number (not applicable)
    80.4
    86.2
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Statistical analysis description
    The analysis purpose of this efficacy endpoint was to assess the noninferiority of switching to F/TAF+3rd Agent relative to maintaining treatment with ABC/3TC+3rd Agent. The difference in percentages and its 95% CI were calculated based on an unconditional exact method using 2 inverted 1-sided tests.
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    556
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    P-value
    		 = 0.069
    Method
    		 Fisher exact
    Parameter type
    		 Difference in Percentages
    Point estimate
    -5.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.2
         upper limit
    		 0.4
    Notes
    [6] - Non-inferiority was assessed using a 2-sided exact 95% CI approach, with a non-inferiority margin of 10%.

    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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    249
    254
    Units: cells/μL
        arithmetic mean (standard deviation)
    -30 ± 152.3
    2 ± 171.2
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.026 [7]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -61
         upper limit
    		 -4
    Notes
    [7] - P-value, difference in least squares means (LSM), and its 95% CI were from ANOVA model with treatment and the third agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    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
    		 F/TAF ABC/3TC
    Number of subjects analysed
    229
    238
    Units: cells/μL
        arithmetic mean (standard deviation)
    -29 ± 160.7
    10 ± 178.2
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    467
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.013 [8]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -70
         upper limit
    		 -8
    Notes
    [8] - P-value, difference in LSM, and its 95% CI were from ANOVA model with treatment and the 3rd agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    Secondary: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48

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    End point title
    		 Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
    End point description
    Participants in the Hip Dual-Energy X-Ray Absorptiometry (DXA) Analysis Set (all participants who are randomized and have received at least one dose of study drug, and have nonmissing baseline hip BMD values) with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 48
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    231
    236
    Units: percent change
        arithmetic mean (standard deviation)
    0.246 ± 2.2914
    0.086 ± 2.3315
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    467
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4 [9]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.179
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.24
         upper limit
    		 0.598
    Notes
    [9] - P-value, difference in LSM, and its 95% CI were from ANOVA model with treatment and the 3rd agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    Secondary: Percent Change From Baseline in Hip BMD at Week 96

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    End point title
    		 Percent Change From Baseline in Hip BMD at Week 96
    End point description
    Participants in the Hip DXA Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 96
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    213
    221
    Units: percent change
        arithmetic mean (standard deviation)
    0.169 ± 2.7277
    0.021 ± 2.7212
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    434
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53 [10]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.165
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.348
         upper limit
    		 0.678
    Notes
    [10] - P-value, difference in LSM, and its 95% CI were from ANOVA model with treatment and the 3rd agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    Secondary: Percent Change From Baseline in Spine BMD at Week 48

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    End point title
    		 Percent Change From Baseline in Spine BMD at Week 48
    End point description
    Participants in the Spine DXA Analysis Set (all participants who are randomized and have received at least one dose of study drug, and have nonmissing baseline spine BMD values) with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 48
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    232
    240
    Units: percent change
        arithmetic mean (standard deviation)
    0.081 ± 3.0051
    -0.052 ± 3.7550
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    472
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.63 [11]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    0.151
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.465
         upper limit
    		 0.767
    Notes
    [11] - P-value, difference in LSM, and its 95% CI were from ANOVA model with treatment and the 3rd agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    Secondary: Percent Change From Baseline in Spine BMD at Week 96

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    End point title
    		 Percent Change From Baseline in Spine BMD at Week 96
    End point description
    Participants in the Spine DXA Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline; Week 96
    End point values
    		 F/TAF ABC/3TC
    Number of subjects analysed
    217
    225
    Units: percent change
        arithmetic mean (standard deviation)
    0.178 ± 3.8881
    0.235 ± 4.3066
    Statistical analysis title
    		 Statistical Analysis - F/TAF vs ABC/3TC
    Comparison groups
    F/TAF v ABC/3TC
    Number of subjects included in analysis
    442
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.89 [12]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LSM
    Point estimate
    -0.056
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.825
         upper limit
    		 0.713
    Notes
    [12] - P-value, difference in LSM, and its 95% CI were from ANOVA model with treatment and the 3rd agent stratum (boosted protease inhibitors vs. others) as fixed effects in the model.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    First dose date to last dose date (maximum duration: 168 weeks) plus 30 days
    Adverse event reporting additional description
    The Safety Analysis Set included all participants who were randomized and received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    F/TAF (Double-Blind Phase)
    Reporting group description
    		 Adverse events reported occurred during the Double-Blind Phase in participants from the F/TAF group, who received F/TAF (200/10 mg) FDC tablet (with boosted 3rd ARV agent) or F/TAF (200/25 mg) FDC tablet (with unboosted 3rd ARV agent) + ABC/3TC placebo tablet once daily.

    Reporting group title
    ABC/3TC (Double-Blind Phase)
    Reporting group description
    		 Adverse events reported occurred during the Double-Blind Phase in participants from the ABC/3TC group, who received ABC/3TC (600/300 mg) FDC tablet + F/TAF placebo tablet once daily + allowed 3rd ARV agent.

    Reporting group title
    Open-Label F/TAF From F/TAF
    Reporting group description
    		 Adverse events reported occurred during the Open-Label Extension Phase in participants who enrolled into the Open-Label Extension Phase from the F/TAF group and received F/TAF (200/10 mg or 200/25 mg) FDC tablet once daily.

    Reporting group title
    Open-Label F/TAF From ABC/3TC
    Reporting group description
    		 Adverse events reported occurred during the Open-Label Extension Phase in participants who enrolled into the Open-Label Extension Phase from the ABC/3TC group and received F/TAF (200/10 mg or 200/25 mg) FDC tablet once daily.

    Serious adverse events
    		 F/TAF (Double-Blind Phase) ABC/3TC (Double-Blind Phase) Open-Label F/TAF From F/TAF Open-Label F/TAF From ABC/3TC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    55 / 280 (19.64%)
    32 / 276 (11.59%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         number of deaths (all causes)
    5
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hodgkin's disease
         subjects affected / exposed
    2 / 280 (0.71%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Lung cancer metastatic
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 cancer
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Anogenital warts
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Bladder transitional cell carcinoma
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Choroid melanoma
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Ganglioneuroma
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Ovarian cancer metastatic
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Prostate cancer
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Rectal cancer
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    2 / 280 (0.71%)
    3 / 276 (1.09%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Chest pain
         subjects affected / exposed
    2 / 280 (0.71%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Asthenia
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Death
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Sudden cardiac death
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Social circumstances
    Substance use
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pulmonary embolism
         subjects affected / exposed
    0 / 280 (0.00%)
    3 / 276 (1.09%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pneumonia aspiration
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.71%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Alcohol abuse
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Depression
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Drug abuse
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Intentional self-injury
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Schizophrenia
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 abuse
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Transaminases increased
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Viral load increased
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Fall
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Femoral neck fracture
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Femur fracture
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Fibula fracture
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Meniscus injury
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Poisoning
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Road traffic accident
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Seroma
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Uterine perforation
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Cardiac disorders
    Coronary artery disease
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Myocardial infarction
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Cardiac failure congestive
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Coronary artery stenosis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pericarditis
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Cerebral infarction
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Epilepsy
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Hydrocephalus
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 encephalopathy
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Presyncope
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Seizure
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Transient ischaemic attack
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Leukocytosis
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Neutropenia
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Diarrhoea
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Faecaloma
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 haemorrhage
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Haematemesis
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Ileus paralytic
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Intestinal ischaemia
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Large intestine perforation
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Oesophageal ulcer
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pancreatitis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pancreatitis acute
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Rectal haemorrhage
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Small intestinal obstruction
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Umbilical hernia
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (1.07%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Nephrolithiasis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Renal colic
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Osteonecrosis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pathological fracture
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Rhabdomyolysis
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    5 / 280 (1.79%)
    2 / 276 (0.72%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 280 (0.36%)
    2 / 276 (0.72%)
    0 / 6 (0.00%)
    0 / 5 (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
    Appendicitis
         subjects affected / exposed
    1 / 280 (0.36%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Gastroenteritis
         subjects affected / exposed
    0 / 280 (0.00%)
    2 / 276 (0.72%)
    0 / 6 (0.00%)
    0 / 5 (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
    Abdominal wall abscess
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Acute hepatitis C
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Clostridium difficile infection
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Dengue fever
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Diarrhoea infectious
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Diverticulitis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Erysipelas
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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 pyelonephritis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Groin abscess
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Herpes zoster oticus
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Oesophageal candidiasis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Peritonitis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Pneumonia legionella
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Postoperative wound infection
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Respiratory tract infection
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Staphylococcal abscess
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Viral myocarditis
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Type 2 diabetes mellitus
         subjects affected / exposed
    2 / 280 (0.71%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Dehydration
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (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
    Hyponatraemia
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    0 / 6 (0.00%)
    0 / 5 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 F/TAF (Double-Blind Phase) ABC/3TC (Double-Blind Phase) Open-Label F/TAF From F/TAF Open-Label F/TAF From ABC/3TC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    190 / 280 (67.86%)
    199 / 276 (72.10%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    15 / 280 (5.36%)
    15 / 276 (5.43%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    15
    15
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    31 / 280 (11.07%)
    25 / 276 (9.06%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    35
    36
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    21 / 280 (7.50%)
    15 / 276 (5.43%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    22
    16
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    30 / 280 (10.71%)
    37 / 276 (13.41%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    38
    43
    0
    0
    Nausea
         subjects affected / exposed
    14 / 280 (5.00%)
    11 / 276 (3.99%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    15
    11
    0
    0
    Vomiting
         subjects affected / exposed
    14 / 280 (5.00%)
    10 / 276 (3.62%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    16
    10
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    34 / 280 (12.14%)
    30 / 276 (10.87%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    41
    40
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    14 / 280 (5.00%)
    17 / 276 (6.16%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    14
    19
    0
    0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 280 (0.36%)
    0 / 276 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    28 / 280 (10.00%)
    29 / 276 (10.51%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    31
    29
    0
    0
    Back pain
         subjects affected / exposed
    24 / 280 (8.57%)
    31 / 276 (11.23%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    26
    32
    0
    0
    Pain in extremity
         subjects affected / exposed
    22 / 280 (7.86%)
    15 / 276 (5.43%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    22
    18
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    11 / 280 (3.93%)
    14 / 276 (5.07%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    11
    15
    0
    0
    Spinal pain
         subjects affected / exposed
    0 / 280 (0.00%)
    1 / 276 (0.36%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    57 / 280 (20.36%)
    49 / 276 (17.75%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    80
    76
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    36 / 280 (12.86%)
    46 / 276 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    53
    63
    0
    0
    Bronchitis
         subjects affected / exposed
    19 / 280 (6.79%)
    14 / 276 (5.07%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    23
    16
    0
    0
    Urinary tract infection
         subjects affected / exposed
    13 / 280 (4.64%)
    18 / 276 (6.52%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    18
    30
    0
    0
    Influenza
         subjects affected / exposed
    12 / 280 (4.29%)
    15 / 276 (5.43%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    14
    16
    0
    0
    Gastroenteritis
         subjects affected / exposed
    11 / 280 (3.93%)
    15 / 276 (5.43%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    12
    17
    0
    0
    Syphilis
         subjects affected / exposed
    15 / 280 (5.36%)
    5 / 276 (1.81%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    16
    5
    0
    0
    Rhinitis
         subjects affected / exposed
    7 / 280 (2.50%)
    6 / 276 (2.17%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    8
    6
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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/29475804
    http://www.ncbi.nlm.nih.gov/pubmed/30932951
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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