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    Clinical Trial Results:
    A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

    Summary
    EudraCT number
    		 2019-000587-23
    Trial protocol
    		 FI   ES   FR   DE   IT  
    Global end of trial date
    27 Feb 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Jan 2026
    First version publication date
    31 Jan 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-8591A-018
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04223791
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 JAPIC-CTI: 205166
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.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
    27 Feb 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Aug 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Feb 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study will evaluate the safety and efficacy of a switch to Doravirine/Islatravir (DOR/ISL) (MK-8591A) (a fixed dose combination of doravirine 100 mg and islatravir 0.75 mg) in participants living with human immunodeficiency virus-1 (HIV-1) virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to DOR/ISL (MK-8591A) will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Feb 2020
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 50 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 37
    Country: Number of subjects enrolled
    Austria: 48
    Country: Number of subjects enrolled
    Canada: 18
    Country: Number of subjects enrolled
    Finland: 10
    Country: Number of subjects enrolled
    France: 66
    Country: Number of subjects enrolled
    Germany: 109
    Country: Number of subjects enrolled
    Italy: 36
    Country: Number of subjects enrolled
    Japan: 9
    Country: Number of subjects enrolled
    Puerto Rico: 23
    Country: Number of subjects enrolled
    Spain: 85
    Country: Number of subjects enrolled
    United States: 202
    Worldwide total number of subjects
    643
    EEA total number of subjects
    354
    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)
    590
    From 65 to 84 years
    53
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Adult participants living with human immunodeficiency virus-1 (HIV-1) who have been virologically suppressed for ≥3 months and receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) with no history of treatment failure were enrolled.

    Period 1
    Period 1 title
    Base Study (Day 1 to Week 144)
    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
    		 DOR/ISL
    Arm description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo to BIC/FTC/TAF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily

    Investigational medicinal product name
    doravirine (DOR)/islatravir (ISL)
    Investigational medicinal product code
    Other name
    MK-8591A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg DOR/ 0.75 ISL fixed dose combination (FDC) single tablet taken orally once daily

    Arm title
    		 BIC/FTC/TAF
    Arm description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo to FDC DOR/ISL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to FDC DOR/ISL in a single tablet taken orally, once daily

    Investigational medicinal product name
    bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily

    Number of subjects in period 1
    		DOR/ISL BIC/FTC/TAF
    Started
    322
    321
    Treated
    322
    319
    Completed
    224
    211
    Not completed
    98
    110
         Adverse event, serious fatal
    2
    -
         Physician decision
    18
    7
         Consent withdrawn by subject
    56
    40
         Unknown
    6
    15
         Sponsor Decision
    11
    39
         Lost to follow-up
    5
    8
         Protocol deviation
    -
    1
    Period 2
    Period 2 title
    Extension Study (Week 144 to Week 168)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DOR/ISL
    Arm description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.
    Arm type
    		 Experimental

    Investigational medicinal product name
    doravirine (DOR)/islatravir (ISL)
    Investigational medicinal product code
    Other name
    MK-8591A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg DOR/ 0.75 ISL fixed dose combination (FDC) single tablet taken orally once daily

    Arm title
    		 BIC/FTC/TAF
    Arm description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily

    Number of subjects in period 2 [1]
    		DOR/ISL BIC/FTC/TAF
    Started
    132
    131
    Completed
    10
    2
    Not completed
    122
    129
         Physician decision
    2
    1
         Consent withdrawn by subject
    28
    2
         Unknown
    -
    1
         Sponsor Decision
    91
    124
         Lost to follow-up
    1
    1
    Notes
    [1] - 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: Subset of participants who completed the base study may have been eligible to enter the study extension.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DOR/ISL
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Reporting group values
    		 DOR/ISL BIC/FTC/TAF Total
    Number of subjects
    		 322 321 643
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 294 296 590
        From 65-84 years
    		 28 25 53
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 47.6 ( 12.6 ) 48.0 ( 11.8 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 105 78 183
        Male
    		 217 243 460
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 3 2 5
        Asian
    		 14 13 27
        Native Hawaiian or Other Pacific Islander
    		 2 0 2
        Black or African American
    		 59 56 115
        White
    		 239 240 479
        More than one race
    		 5 7 12
        Unknown or Not Reported
    		 0 3 3
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 64 55 119
        Not Hispanic or Latino
    		 256 261 517
        Unknown or Not Reported
    		 2 5 7

    End points

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    End points reporting groups
    Reporting group title
    DOR/ISL
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.
    Reporting group title
    DOR/ISL
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Primary: Percentage of Participants with Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 copies/mL at Week 48

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    End point title
    		 Percentage of Participants with Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 copies/mL at Week 48
    End point description
    The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    0.6
    0.3
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    P-value
    		 < 0.001 [2]
    Method
    		 Unstratified Miettinen and Nurminen
    Parameter type
    		 Estimated difference
    Point estimate
    0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.19
         upper limit
    		 1.96
    Notes
    [1] - Non-inferiority is concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI for the difference in the percentage of participants with HIV-1 RNA ≥50 copies/mL (DOR/ISL-BIC/FTC/TAF) is less than 4 percentage points.
    [2] - p-value for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method.

    Primary: Percentage of Participants With One or More Adverse Events (AEs) up to Week 48

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    End point title
    		 Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented. The analysis population consisted of all randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.
    End point type
    Primary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    71.1
    74.6
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 Difference in % (DOR/ISL- BIC/FTC/TAF)
    Point estimate
    -3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.4
         upper limit
    		 3.4
    Notes
    [3] - Difference between treatment groups. Based on Miettinen and Nurminen method.

    Primary: Percentage of Participants who Discontinued Study Intervention Due to an AE up to Week 48

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    End point title
    		 Percentage of Participants who Discontinued Study Intervention Due to an AE up to Week 48
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE up to week 48 is presented. The analysis population consisted of all randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.
    End point type
    Primary
    End point timeframe
    Up to 48 weeks
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    2.5
    2.5
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 Difference in % (DOR/ISL- BIC/FTC/TAF)
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 2.6
    Notes
    [4] - Difference between treatment groups; based on Miettinen and Nurminen method

    Secondary: Percentage of Participants with HIV-1 RNA ≥50 copies/mL at Week 96

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    End point title
    		 Percentage of Participants with HIV-1 RNA ≥50 copies/mL at Week 96
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    0.6
    0.3
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    P-value
    		 < 0.001 [6]
    Method
    		 Unstratified Miettinen and Nurminen
    Parameter type
    		 Estimated Difference
    Point estimate
    0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.19
         upper limit
    		 1.96
    Notes
    [5] - Non-inferiority is concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI for the difference in the percentage of participants with HIV-1 RNA ≥50 copies/mL (DOR/ISL minus BIC/FTC/TAF) is less than 4 percentage points. Estimated difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.
    [6] - p-value for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method.

    Secondary: Percentage of Participants with HIV-1 RNA ≥50 copies/mL at Week 144

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    End point title
    		 Percentage of Participants with HIV-1 RNA ≥50 copies/mL at Week 144
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    0.9
    1.3
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.36
         upper limit
    		 1.6
    Notes
    [7] - Non-inferiority is concluded if the upper bound of the 2-sided multiplicity-adjusted 95% CI for the difference in the percentage of participants with HIV-1 RNA ≥50 copies/mL (DOR/ISL minus BIC/FTC/TAF) is less than 4 percentage points. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 48

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    End point title
    		 Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 48
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    93.8
    94.4
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [8]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.38
         upper limit
    		 3.21
    Notes
    [8] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences and CIs for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 48

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    End point title
    		 Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 48
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 48 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    93.2
    94.0
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [9]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.81
         upper limit
    		 3.02
    Notes
    [9] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences and CIs for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 96

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    End point title
    		 Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 96
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    85.1
    90.9
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -5.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.94
         upper limit
    		 -0.79
    Notes
    [10] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences, CIs and p-value for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 96

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    End point title
    		 Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 96
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 96 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    84.8
    90.9
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -6.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.28
         upper limit
    		 -1.08
    Notes
    [11] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences, CIs and p-value for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 144

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    End point title
    		 Percentage of Participants with HIV-1 RNA <50 copies/mL at Week 144
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    51.9
    65.5
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -13.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.11
         upper limit
    		 -6.04
    Notes
    [12] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences and CIs for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 144

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    End point title
    		 Percentage of Participants with HIV-1 RNA <40 copies/mL at Week 144
    End point description
    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 144 is presented using the FDA snapshot missing data approach. The analysis population consisted of all participants who received ≥1 dose of study intervention. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    51.9
    65.5
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    641
    Analysis specification
    Pre-specified
    Analysis type
    		 other [13]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -13.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.11
         upper limit
    		 -6.04
    Notes
    [13] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The estimated differences, CIs and p-value for the treatment differences in percent response were calculated using the unstratified Miettinen and Nurminen method. Estimated Difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Mean Change from Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48

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    End point title
    		 Mean Change from Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48
    End point description
    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and 48 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 48 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline. The analysis population consisted of all participants who received ≥1 dose of study intervention and had data available, including baseline data available, for CD4+ T-cell count at Week 48. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    301
    298
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    -19.66 (-39.78 to 0.45)
    40.51 (20.66 to 60.36)
    Statistical analysis title
    		 Mean Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    599
    Analysis specification
    Pre-specified
    Analysis type
    		 other [14]
    Method
    Parameter type
    		 Mean difference (DOR/ISL-BIC/FTC/TAF)
    Point estimate
    -68.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -94.75
         upper limit
    		 -41.43
    Notes
    [14] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The Confidence Intervals (CIs) for mean difference in CD4+ T-cell count change from baseline were based on Analysis of Covariance (ANCOVA) model adjusted by baseline CD4+ T-cell count and treatment group.

    Secondary: Mean Change from Baseline in CD4+ T-cell count at Week 144

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    End point title
    		 Mean Change from Baseline in CD4+ T-cell count at Week 144
    End point description
    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and 144 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 144 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline. The analysis population consisted of all participants who received ≥1 dose of study intervention and had data available, including baseline data available, for CD4+ T-cell count at Week 144. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    170
    213
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    0.48 (-28.69 to 29.64)
    66.25 (38.78 to 93.73)
    Statistical analysis title
    		 Mean Difference in Treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    383
    Analysis specification
    Pre-specified
    Analysis type
    		 other [15]
    Method
    Parameter type
    		 Mean difference (DOR/ISL-BIC/FTC/TAF)
    Point estimate
    -78.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -114.63
         upper limit
    		 -41.63
    Notes
    [15] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The CIs for mean difference in CD4+ T-cell count change from baseline were based on ANCOVA model adjusted by baseline CD4+ T-cell count and treatment group.

    Secondary: Mean Change from Baseline in CD4+ T-cell count at Week 96

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    End point title
    		 Mean Change from Baseline in CD4+ T-cell count at Week 96
    End point description
    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and 96 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 96 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline. The analysis population consisted of all participants who received ≥1 dose of study intervention and had data available, including baseline data available, for CD4+ T-cell count at Week 96. Participants were included in the treatment group to which they were randomized.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    273
    290
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    5.36 (-19.71 to 30.42)
    62.67 (40.44 to 84.90)
    Statistical analysis title
    		 Mean Difference in Treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    563
    Analysis specification
    Pre-specified
    Analysis type
    		 other [16]
    Method
    Parameter type
    		 Mean difference (DOR/ISL-BIC/FTC/TAF)
    Point estimate
    -65.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -97.02
         upper limit
    		 -33.89
    Notes
    [16] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The CIs for mean difference in CD4+ T-cell count change from baseline were based on ANCOVA model adjusted by baseline CD4+ T-cell count and treatment group.

    Secondary: Number of Participants with evidence of viral drug resistance-associated substitutions at Week 96

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    End point title
    		 Number of Participants with evidence of viral drug resistance-associated substitutions at Week 96
    End point description
    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance at week 96 is presented. The analysis population consisted of participants with data available at Week 96. Per protocol, participants who met the definition of confirmed virologic rebound (two consecutive [2 to 4 weeks apart] occurrences of HIV-1 RNA ≥200 copies/mL) at any time during the study or who discontinued study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation. Participants for whom available genotypic or phenotypic data showed evidence of resistance, irrespective of viral load, were also included.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    2 [17]
    0 [18]
    Units: Participants
    0
    Notes
    [17] - Participants who met protocol-specified criteria for viral drug resistance analysis in DOR/ISL
    [18] - Participants who met protocol-specified criteria for viral drug resistance analysis in BIC/FTC/TAF
    No statistical analyses for this end point

    Secondary: Number of Participants with Viral Drug Resistance-associated Substitutions at Week 48

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    End point title
    		 Number of Participants with Viral Drug Resistance-associated Substitutions at Week 48
    End point description
    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL having genotypic or phenotypic evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance is presented. The analysis population consisted of participants with data available at Week 48. Per protocol, participants who met the definition of confirmed virologic rebound (two consecutive [2 to 4 weeks apart] occurrences of HIV-1 RNA ≥200 copies/mL) at any time during the study or who discontinued study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation. Participants for whom available genotypic or phenotypic data showed evidence of resistance, irrespective of viral load, were also included.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    1 [19]
    0 [20]
    Units: Participants
    0
    Notes
    [19] - Participants who met protocol-specified criteria for viral drug resistance analysis in DOR/ISL
    [20] - Participants who met protocol-specified criteria for viral drug resistance analysis in BIC/FTC/TAF
    No statistical analyses for this end point

    Secondary: Number of Participants with evidence of viral drug resistance-associated substitutions at Week 144

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    End point title
    		 Number of Participants with evidence of viral drug resistance-associated substitutions at Week 144
    End point description
    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance at week 144 is presented. The analysis population consisted of participants with data available at Week 144. Per protocol, participants who met the definition of confirmed virologic rebound (two consecutive [2 to 4 weeks apart] occurrences of HIV-1 RNA ≥200 copies/mL) at any time during the study or who discontinued study intervention for another reason and have HIV-1 RNA ≥200 copies/mL at the time of discontinuation. Participants for whom available genotypic or phenotypic data showed evidence of resistance, irrespective of viral load, were also included.
    End point type
    Secondary
    End point timeframe
    Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    2 [21]
    0 [22]
    Units: Participants
    0
    Notes
    [21] - Participants who met protocol-specified criteria for viral drug resistance analysis in DOR/ISL
    [22] - Participants who met protocol-specified criteria for viral drug resistance analysis in BIC/FTC/TAF
    No statistical analyses for this end point

    Secondary: Change from Baseline in Body Weight at Week 48

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    End point title
    		 Change from Baseline in Body Weight at Week 48
    End point description
    Body weight was measured and recorded at baseline and week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 48 is presented. The analysis population consisted of participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received. The analysis population included participants with baseline and at least one postbaseline test result and had data available for this outcome measure at Week 48.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 48
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    306
    302
    Units: kilogram (kg)
        arithmetic mean (standard deviation)
    0.23 ( 4.19 )
    0.55 ( 4.40 )
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    608
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    P-value
    		 = 0.392 [24]
    Method
    		 ANCOVA
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.99
         upper limit
    		 0.39
    Notes
    [23] - ANCOVA Model included terms for baseline weight, sex, race, and treatment. Treatment difference is treatment difference for DOR/ISL group-BIC/FTC/TAF group.
    [24] - Model included terms for baseline weight, sex, race, and treatment.

    Secondary: Change from Baseline in Body Weight at Week 96

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    End point title
    		 Change from Baseline in Body Weight at Week 96
    End point description
    Body weight was measured and recorded at baseline and week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 96 is presented. The analysis population consisted of participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received. The analysis population included participants with baseline and at least one postbaseline test result and had data available for this outcome measure at Week 96.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 96
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    277
    293
    Units: kilogram (kg)
        arithmetic mean (standard deviation)
    0.29 ( 5.33 )
    0.72 ( 5.72 )
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    570
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    P-value
    		 = 0.3263 [26]
    Method
    		 ANCOVA
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.34
         upper limit
    		 0.45
    Notes
    [25] - ANCOVA model included terms for baseline weight, sex, race, and treatment. Treatment difference is treatment difference for DOR/ISL group minus BIC/FTC/TAF group.
    [26] - Model included terms for baseline weight, sex, race, and treatment.

    Secondary: Change from Baseline in Body Weight at Week 144

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    End point title
    		 Change from Baseline in Body Weight at Week 144
    End point description
    Body weight was measured and recorded at baseline and week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 144 is presented. The analysis population consisted of participants who received ≥1 dose of study intervention and were included in the treatment group corresponding to the study intervention received. The analysis population included participants with baseline and at least one postbaseline test result and had data available for this outcome measure at Week 144.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 144
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    216
    236
    Units: kilogram (kg)
        arithmetic mean (standard deviation)
    0.63 ( 6.67 )
    0.84 ( 6.41 )
    Statistical analysis title
    		 Difference between treatment groups
    Comparison groups
    DOR/ISL v BIC/FTC/TAF
    Number of subjects included in analysis
    452
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.33
         upper limit
    		 1.06
    Notes
    [27] - Type of statistical test 'other' denotes no hypothesis testing was conducted. The 95% CIs for treatment difference were calculated from ANCOVA model with terms for baseline weight, sex, race, and treatment. Treatment difference for DOR/ISL group minus BIC/FTC/TAF group.

    Secondary: Percentage of Participants With One or More AEs

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    End point title
    		 Percentage of Participants With One or More AEs
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced at least one or more AEs is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The analysis population consisted of all randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.
    End point type
    Secondary
    End point timeframe
    Up to approximately 55 months
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    96.3
    94.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Discontinued Study Intervention Due to an AE

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    End point title
    		 Percentage of Participants who Discontinued Study Intervention Due to an AE
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The analysis population consisted of all randomized participants who received ≥1 dose of study intervention. Participants were included in the treatment group corresponding to the study intervention received.
    End point type
    Secondary
    End point timeframe
    Up to approximately 40 months
    End point values
    		 DOR/ISL BIC/FTC/TAF
    Number of subjects analysed
    322
    319
    Units: Percentage of Participants
        number (not applicable)
    22.0
    6.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 55 months
    Adverse event reporting additional description
    All cause mortality: all randomized participants; AEs: all randomized participants who got ≥1 dose of study drug. Reported by base & extension. Per protocol, participants with specific drops in CD4+/total lymphocyte count reported as ‘post treatment follow up’; all pregnancy-related AEs were collected & reported by arm that participants enrolled.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    DOR/ISL: Base Study Week 0 - Week 48
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    DOR/ISL: Base Study Week 48-Week 96
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    DOR/ISL: Base Study Week 96-Week 144
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    DOR/ISL: Open-Label Extension Week 144-Week 168
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    DOR/ISL: Post-Treatment Follow-Up
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received a once daily (QD) fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and a placebo to BIC/FTC/TAF for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF: Base Study Week 0 - Week 48
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF: Base Study Week 48 - Week 96
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF: Base Study Week 96 - Week 144
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF: Open-Label Extension Week 144 - Week 168
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Reporting group title
    BIC/FTC/TAF: Post-Treatment Follow-Up
    Reporting group description
    		 Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months with no history of treatment failure who were previously treated with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) received once daily (QD) 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to fixed dose combination (FDC) DOR/ISL for 96 weeks. At Week 144, participants who consent to enter the optional open-label study extension will continue to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.

    Serious adverse events
    		 DOR/ISL: Base Study Week 0 - Week 48 DOR/ISL: Base Study Week 48-Week 96 DOR/ISL: Base Study Week 96-Week 144 DOR/ISL: Open-Label Extension Week 144-Week 168 DOR/ISL: Post-Treatment Follow-Up BIC/FTC/TAF: Base Study Week 0 - Week 48 BIC/FTC/TAF: Base Study Week 48 - Week 96 BIC/FTC/TAF: Base Study Week 96 - Week 144 BIC/FTC/TAF: Open-Label Extension Week 144 - Week 168 BIC/FTC/TAF: Post-Treatment Follow-Up
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 322 (4.35%)
    19 / 305 (6.23%)
    7 / 266 (2.63%)
    0 / 132 (0.00%)
    3 / 196 (1.53%)
    16 / 319 (5.02%)
    11 / 301 (3.65%)
    6 / 281 (2.14%)
    1 / 131 (0.76%)
    0 / 152 (0.00%)
         number of deaths (all causes)
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer metastatic
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    1 / 196 (0.51%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipoma
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Social circumstances
    Imprisonment
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Substance use
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst torsion
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Bipolar disorder
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug abuse
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular pseudoaneurysm
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arteriospasm coronary
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    2 / 322 (0.62%)
    1 / 305 (0.33%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    1 / 196 (0.51%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brachial plexopathy
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thalamic stroke
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic artery aneurysm
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    1 / 131 (0.76%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myositis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    1 / 196 (0.51%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acute hepatitis B
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 322 (0.31%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 322 (0.31%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis bacterial
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis escherichia
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Giardiasis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurosyphilis
         subjects affected / exposed
    1 / 322 (0.31%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    1 / 301 (0.33%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    1 / 266 (0.38%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 322 (0.00%)
    0 / 305 (0.00%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    1 / 319 (0.31%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 322 (0.00%)
    1 / 305 (0.33%)
    0 / 266 (0.00%)
    0 / 132 (0.00%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    0 / 301 (0.00%)
    0 / 281 (0.00%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DOR/ISL: Base Study Week 0 - Week 48 DOR/ISL: Base Study Week 48-Week 96 DOR/ISL: Base Study Week 96-Week 144 DOR/ISL: Open-Label Extension Week 144-Week 168 DOR/ISL: Post-Treatment Follow-Up BIC/FTC/TAF: Base Study Week 0 - Week 48 BIC/FTC/TAF: Base Study Week 48 - Week 96 BIC/FTC/TAF: Base Study Week 96 - Week 144 BIC/FTC/TAF: Open-Label Extension Week 144 - Week 168 BIC/FTC/TAF: Post-Treatment Follow-Up
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 322 (26.40%)
    104 / 305 (34.10%)
    151 / 266 (56.77%)
    34 / 132 (25.76%)
    14 / 196 (7.14%)
    93 / 319 (29.15%)
    86 / 301 (28.57%)
    101 / 281 (35.94%)
    13 / 131 (9.92%)
    0 / 152 (0.00%)
    Investigations
    CD4 lymphocytes decreased
         subjects affected / exposed
    1 / 322 (0.31%)
    28 / 305 (9.18%)
    63 / 266 (23.68%)
    15 / 132 (11.36%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    4 / 301 (1.33%)
    28 / 281 (9.96%)
    6 / 131 (4.58%)
    0 / 152 (0.00%)
         occurrences all number
    1
    28
    75
    16
    0
    0
    4
    35
    6
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 322 (0.31%)
    32 / 305 (10.49%)
    86 / 266 (32.33%)
    21 / 132 (15.91%)
    0 / 196 (0.00%)
    0 / 319 (0.00%)
    8 / 301 (2.66%)
    28 / 281 (9.96%)
    6 / 131 (4.58%)
    0 / 152 (0.00%)
         occurrences all number
    1
    32
    108
    21
    0
    0
    8
    31
    6
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 322 (1.86%)
    3 / 305 (0.98%)
    5 / 266 (1.88%)
    1 / 132 (0.76%)
    0 / 196 (0.00%)
    16 / 319 (5.02%)
    6 / 301 (1.99%)
    3 / 281 (1.07%)
    1 / 131 (0.76%)
    0 / 152 (0.00%)
         occurrences all number
    6
    3
    5
    1
    0
    16
    6
    3
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    26 / 322 (8.07%)
    14 / 305 (4.59%)
    3 / 266 (1.13%)
    1 / 132 (0.76%)
    1 / 196 (0.51%)
    22 / 319 (6.90%)
    6 / 301 (1.99%)
    1 / 281 (0.36%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences all number
    43
    38
    7
    1
    9
    22
    6
    2
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    8 / 322 (2.48%)
    7 / 305 (2.30%)
    7 / 266 (2.63%)
    2 / 132 (1.52%)
    2 / 196 (1.02%)
    20 / 319 (6.27%)
    7 / 301 (2.33%)
    2 / 281 (0.71%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences all number
    8
    7
    7
    2
    3
    21
    7
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    13 / 322 (4.04%)
    9 / 305 (2.95%)
    9 / 266 (3.38%)
    0 / 132 (0.00%)
    1 / 196 (0.51%)
    17 / 319 (5.33%)
    6 / 301 (1.99%)
    8 / 281 (2.85%)
    1 / 131 (0.76%)
    0 / 152 (0.00%)
         occurrences all number
    14
    11
    9
    0
    1
    17
    6
    8
    1
    0
    Arthralgia
         subjects affected / exposed
    16 / 322 (4.97%)
    8 / 305 (2.62%)
    9 / 266 (3.38%)
    1 / 132 (0.76%)
    1 / 196 (0.51%)
    19 / 319 (5.96%)
    14 / 301 (4.65%)
    8 / 281 (2.85%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences all number
    20
    9
    10
    1
    1
    20
    15
    9
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    19 / 322 (5.90%)
    40 / 305 (13.11%)
    33 / 266 (12.41%)
    2 / 132 (1.52%)
    5 / 196 (2.55%)
    18 / 319 (5.64%)
    45 / 301 (14.95%)
    46 / 281 (16.37%)
    0 / 131 (0.00%)
    0 / 152 (0.00%)
         occurrences all number
    19
    42
    35
    2
    5
    19
    47
    47
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    9 / 322 (2.80%)
    11 / 305 (3.61%)
    16 / 266 (6.02%)
    1 / 132 (0.76%)
    4 / 196 (2.04%)
    3 / 319 (0.94%)
    11 / 301 (3.65%)
    10 / 281 (3.56%)
    3 / 131 (2.29%)
    0 / 152 (0.00%)
         occurrences all number
    11
    12
    17
    1
    7
    3
    11
    10
    3
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Jun 2020
    Amendment 02: The protocol was amended to: (1) update the hypothesis testing strategy in the statistical analysis plan, (2) update the prohibited concomitant therapies, and (3) allow participants to rescreen one time following approval from the Sponsor.
    14 May 2021
    Amendment 03: The protocol was amended to: (1) extend study intervention, open-label, from 96 weeks to 144 weeks for all participants, (2) add option for Group 2 to receive open-label DOR/ISL from Week 144 to Week 156 (a 12-week safety monitoring period before being offered enrollment in DOR/ISL rollover study), (3) offer the option to continue study intervention for participants who become pregnant, (4) add a discontinuation criterion if a participant chooses to breastfeed.
    15 Feb 2022
    Amendment 06: Given the findings of decreases in CD4+ T-cell and total lymphocyte counts in clinical studies evaluating ISL, the protocol is being amended to increase the frequency of monitoring of CD4+ T-cell and total lymphocyte counts and to specify the management of participants who meet protocol-defined decreases in CD4+ T-cell and/or total lymphocyte counts.
    30 Nov 2022
    Amendment 08: This protocol was amended to allow Group 1/Group 2 participants who continue to benefit (as determined by the investigator) from their assigned study intervention to continue their assigned study intervention through a study extension after Week 144. This extension will continue for up to 24 additional weeks (up to maximum Week 168) or until participants have the option to enroll in a DOR/ISL 100-mg/0.25-mg study; whichever is sooner. Participants choosing not to enroll in a DOR/ISL 100 mg/0.25 mg study, will transition to commercially available ART as soon as possible.
    30 May 2024
    Amendment 09: The protocol was amended to revise the post-treatment management of participants with specific decreases in CD4+ T-cell or total lymphocyte counts. The recovery criteria were revised to account for normal physiologic variability in CD4+ T-cell or total lymphocyte counts and the frequency of monitoring was updated to minimize the burden on study participants

    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
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