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    Clinical Trial Results:
    A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects

    Summary
    EudraCT number
    		 2014-003382-17
    Trial protocol
    		 DE   GB   PT   DK   NL   BE   ES  
    Global end of trial date
    07 Sep 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Sep 2024
    First version publication date
    07 Sep 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-1439A-021
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02403674
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.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
    07 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis was that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48.
    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
    05 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Belgium: 7
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    Chile: 49
    Country: Number of subjects enrolled
    Colombia: 41
    Country: Number of subjects enrolled
    Denmark: 6
    Country: Number of subjects enrolled
    Germany: 25
    Country: Number of subjects enrolled
    Guatemala: 20
    Country: Number of subjects enrolled
    Honduras: 7
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Mexico: 27
    Country: Number of subjects enrolled
    New Zealand: 7
    Country: Number of subjects enrolled
    Peru: 32
    Country: Number of subjects enrolled
    Portugal: 27
    Country: Number of subjects enrolled
    Russian Federation: 54
    Country: Number of subjects enrolled
    South Africa: 66
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    Switzerland: 11
    Country: Number of subjects enrolled
    Taiwan: 37
    Country: Number of subjects enrolled
    Thailand: 74
    Country: Number of subjects enrolled
    United Kingdom: 32
    Country: Number of subjects enrolled
    United States: 176
    Worldwide total number of subjects
    734
    EEA total number of subjects
    81
    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)
    730
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Treatment-naïve participants with HIV-1 infection have been recruited at 141 study sites worldwide. The present results include results from the base study (first 96-weeks of the study) along with study extension 1 (week 96 - 192), study extension 2 (week 192 - 288), and study extension 3 (week 288 - 384).

    Pre-assignment
    Screening details
    		 Randomization in base study was stratified by screening HIV-1 ribonucleic acid (RNA [≤1000,000 or >100,000 copies/mL]), and Chronic Hepatitis B and/or C infection status (yes or no).

    Period 1
    Period 1 title
    Base Study
    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
    		 MK-1439A (DOR/3TC/TDF from Day 1)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets matched to ATRIPLA™ q.d.

    Arm title
    		 ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo tablets matched to doravirine, tenofovir, lamivudine.

    Investigational medicinal product name
    ATRIPLA™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One ATRIPLA™ tablet taken by mouth.

    Number of subjects in period 1
    		MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Started
    368
    366
    Treated
    364
    364
    Completed
    296
    276
    Not completed
    72
    90
         Consent withdrawn by subject
    10
    17
         Physician decision
    2
    2
         Adverse event, non-fatal
    11
    26
         Death
    1
    4
         Pregnancy
    2
    2
         Noncompliance with study drug
    1
    4
         Not treated with study drug
    4
    2
         Lost to follow-up
    6
    8
         Lack of efficacy
    31
    23
         Protocol deviation
    4
    2
    Period 2
    Period 2 title
    Study Extension 1 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-1439A (DOR/3TC/TDF from Day 1)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.

    Arm title
    		 ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.

    Number of subjects in period 2 [1]
    		MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Started
    291
    269
    Completed
    230
    205
    Not completed
    61
    64
         Physician decision
    2
    5
         Consent withdrawn by subject
    11
    13
         Adverse event, non-fatal
    1
    4
         Availability of study drug locally
    22
    19
         Death
    1
    -
         Pregnancy
    4
    2
         Non-Compliance with study drug
    2
    3
         Lost to follow-up
    8
    5
         Lack of efficacy
    10
    13
    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: not all study participants continued into optional study extension 1.
    Period 3
    Period 3 title
    Study Extension 2 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-1439A (DOR/3TC/TDF from Day 1)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth

    Arm title
    		 ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth

    Number of subjects in period 3 [2]
    		MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Started
    192
    173
    Completed
    150
    132
    Not completed
    42
    41
         Physician decision
    1
    1
         Consent withdrawn by subject
    8
    6
         Availability of study drug locally
    27
    23
         Death
    2
    2
         Pregnancy
    -
    1
         Non-Compliance with study drug
    2
    -
         Lost to follow-up
    1
    7
         Lack of efficacy
    1
    1
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: not all study participants continued into optional study extension 2.
    Period 4
    Period 4 title
    Study Extension 3 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MK-1439A (DOR/3TC/TDF from Day 1)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth

    Arm title
    		 ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Arm description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth

    Number of subjects in period 4 [3]
    		MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Started
    121
    111
    Completed
    100
    85
    Not completed
    21
    26
         Physician decision
    1
    5
         Consent withdrawn by subject
    1
    3
         Availability of study drug locally
    14
    13
         Pregnancy
    -
    1
         Lost to follow-up
    5
    4
    Notes
    [3] - 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: not all study participants continued into optional study extension 3.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    MK-1439A (DOR/3TC/TDF from Day 1)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group title
    ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96) Total
    Number of subjects
    		 368 366 734
    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)
    		 366 364 730
        From 65-84 years
    		 2 2 4
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 33.6 ( 10.5 ) 32.7 ( 9.9 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 59 54 113
        Male
    		 309 312 621
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 9 6 15
        Asian
    		 59 64 123
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 70 69 139
        White
    		 178 171 349
        More than one race
    		 52 56 108
        Unknown or Not Reported
    		 0 0 0
    Baseline cluster of differentiation 4 (CD4) cell counts
    The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy.
    Units: cells/mm^3
        arithmetic mean (standard deviation)
    		 434.9 ( 217.9 ) 415.5 ( 210.6 ) -
    Baseline fasting low-density lipoprotein cholesterol (LDL-C)
    Participants fasted for ≥8 hours prior to LDL-C measurement on Day 1. The analysis population consisted of all randomized participants with baseline data available.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 92.08 ( 32.32 ) 90.47 ( 30.64 ) -
    Baseline fasting non-high-density lipoprotein cholesterol (non-HDL-C)
    Participants fasted for ≥8 hours prior to non-HDL-C measurement on Day 1. The analysis population consisted of all randomized participants with baseline data available.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 115.39 ( 34.67 ) 114.63 ( 33.55 ) -
    Baseline fasting cholesterol
    Participants fasted for ≥8 hours prior to cholesterol measurement on Day 1. The analysis population consisted of all randomized participants with baseline data available.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 157.29 ( 36.43 ) 156.07 ( 36.51 ) -
    Baseline fasting triglycerides
    Participants fasted for ≥8 hour prior to triglycerides measurement on Day 1. The analysis population consisted of all randomized participants with baseline data available.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 120.85 ( 83.06 ) 123.23 ( 82.73 ) -
    Baseline fasting high-density lipoprotein cholesterol (HDL-C)
    Participants fasted for ≥8 hours prior to HDL-C measurement on Day 1. Description: Participants fasted for ≥8 hours prior to HDL-C measurement on Day 1. The analysis population consisted of all randomized participants with baseline data available.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 41.90 ( 11.67 ) 41.44 ( 13.08 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    MK-1439A (DOR/3TC/TDF from Day 1)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group title
    ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Reporting group title
    MK-1439A (DOR/3TC/TDF from Day 1)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group title
    ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Reporting group title
    MK-1439A (DOR/3TC/TDF from Day 1)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group title
    ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).
    Reporting group title
    MK-1439A (DOR/3TC/TDF from Day 1)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Reporting group title
    ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384).

    Primary: Percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48

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    End point title
    		 Percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48
    End point description
    The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach in which all missing data are considered treatment failures, regardless of the reason. The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
        number (not applicable)
    84.3
    80.8
    Statistical analysis title
    		 Non-inferiority Analysis for MK-1439A
    Statistical analysis description
    The 95% CIs for difference in percentages were calculated using stratum-adjusted Mantel-Haenszel method for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL).
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    3.537
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.951
         upper limit
    		 9.026
    Notes
    [1] - Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10.

    Primary: Percentage of participants with Tier-1 neuropsychiatric adverse events (AEs)

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    End point title
    		 Percentage of participants with Tier-1 neuropsychiatric adverse events (AEs)
    End point description
    The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included "dizziness", "sleep disorders and disturbances", and "altered sensorium" (including disturbance in attention). The analysis population consists of all randomized participants who received ≥1 dose of study medication.
    End point type
    Primary
    End point timeframe
    Up to Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
    number (not applicable)
        Dizziness
    8.8
    37.1
        Sleep disorders and disturbances
    12.1
    25.5
        Altered sensorium
    4.4
    8.2
    Statistical analysis title
    		 Superiority Analysis of neuropsychiatric AEs
    Statistical analysis description
    The 95% CIs for difference (dizziness difference) in percentages were calculated Miettinen and Nurminen method.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.001 [3]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Difference in percentages
    Point estimate
    -28.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34
         upper limit
    		 -22.5
    Notes
    [2] - Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. 95% CIs were calculated using the Miettinen and Nurminen method.
    [3] - 2-sided P-value
    Statistical analysis title
    		 Superiority Analysis of neuropsychiatric AE's
    Statistical analysis description
    The 95% CIs for difference (sleep disorders and disturbances difference) in percentages were calculated Miettinen and Nurminen method.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 < 0.001 [5]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Difference in percentages
    Point estimate
    -13.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.1
         upper limit
    		 -7.9
    Notes
    [4] - Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497.
    [5] - 2-sided P-value
    Statistical analysis title
    		 Superiority Analysis of neuropsychiatric AE's
    Statistical analysis description
    The 95% CIs for difference (Altered sensorium difference) in percentages were calculated Miettinen and Nurminen method.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.033 [7]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Difference in percentages
    Point estimate
    -3.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.6
         upper limit
    		 -0.3
    Notes
    [6] - Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497.
    [7] - 2-sided P-value

    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 percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 96 were be determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses. The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of participants
        number (confidence interval 95%)
    77.5 (72.8 to 81.7)
    73.6 (68.8 to 78.1)
    Statistical analysis title
    		 Non-inferiority analysis for MK-1439A
    Statistical analysis description
    The 95% CIs for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL).
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    3.815
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.412
         upper limit
    		 10.042
    Notes
    [8] - Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10.

    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 percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach in which all missing data are considered treatment failures, regardless of the reason. The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
        number (confidence interval 95%)
    83.8 (79.6 to 87.4)
    79.7 (75.2 to 83.7)
    Statistical analysis title
    		 Non-inferiority analysis for MK-1439A
    Statistical analysis description
    The 95% CIs for difference in percentages were calculated using stratum-adjusted Mantel-Haenszel method for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL).
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 9.7
    Notes
    [9] - Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10.

    Secondary: Change from baseline in CD4 cell counts at Week 48

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    End point title
    		 Change from baseline in CD4 cell counts at Week 48
    End point description
    The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm^3, and percent change was then calculated as [(Baseline counts - Week 48 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay. The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline and Week 48 CD4 data available.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    344
    329
    Units: Percentage Change from Baseline
        arithmetic mean (confidence interval 95%)
    198.4 (180.2 to 216.7)
    188.4 (169.5 to 207.2)
    Statistical analysis title
    		 Superiority analysis for MK-1439A
    Statistical analysis description
    95% CIs were calculated based on t-distribution.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    673
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [10]
    Method
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    10.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.1
         upper limit
    		 36.3
    Notes
    [10] - Superiority was declared when group difference (MK-1439A-ATRIPLA®) was a positive value.

    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 percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses. The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of participants
        number (confidence interval 95%)
    76.1 (71.4 to 80.4)
    72.8 (67.9 to 77.3)
    Statistical analysis title
    		 Non-inferiority analysis for MK-1439A
    Statistical analysis description
    The 95% CIs for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (HIV-1 RNA ≤100,000 or >100,000 copies/mL).
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    3.268
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.057
         upper limit
    		 9.593
    Notes
    [11] - Non-inferiority was declared if the lower bound of the 95% CI of the mean treatment difference was greater than -10.

    Secondary: Change from baseline in CD4 cell counts at Week 96

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    End point title
    		 Change from baseline in CD4 cell counts at Week 96
    End point description
    The mean change from baseline in CD4 cell counts at Week 96 was assessed using the OF approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 were measured and expressed as cells/mm^3, and percent change was calculated as [(Baseline counts - Week 96 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay. The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline and week 96 CD4 data available.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 96
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    337
    311
    Units: Percentage Change from Baseline
        arithmetic mean (confidence interval 95%)
    237.7 (214.9 to 260.6)
    223.0 (198.4 to 247.6)
    Statistical analysis title
    		 Superiority analysis for MK-1439A
    Statistical analysis description
    The 95% CIs were calculated based on t-distribution.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    648
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    Method
    Parameter type
    		 Diff in mean % change from baseline
    Point estimate
    14.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.7
         upper limit
    		 48.2
    Notes
    [12] - Superiority was declared when group difference (MK-1439A-ATRIPLA) was a positive value.

    Secondary: Percentage of participants discontinuing from study medication due to an AE(s)

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    End point title
    		 Percentage of participants discontinuing from study medication due to an AE(s)
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population consisted of all randomized participants who received ≥1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of participants
        number (not applicable)
    3.0
    6.6
    Statistical analysis title
    		 Diff in % analysis in participant discontinuation
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 other [13]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    -3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.9
         upper limit
    		 -0.5
    Notes
    [13] - Difference in percentage of participants with ≥1 AE(s)

    Secondary: Percentage of participants experiencing ≥1 AE

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    End point title
    		 Percentage of participants experiencing ≥1 AE
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population consisted of all randomized participants who received ≥1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of participants
        number (not applicable)
    82.7
    90.7
    Statistical analysis title
    		 Diff in % analysis vs. ATRIPLA™
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 other [14]
    Method
    Parameter type
    		 Difference in percentages
    Point estimate
    -8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13
         upper limit
    		 -3.1
    Notes
    [14] - Difference in percentage of participants with ≥1 AE(s)

    Secondary: Percentage of participants with Tier-2 neuropsychiatric AEs

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    End point title
    		 Percentage of participants with Tier-2 neuropsychiatric AEs
    End point description
    The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included "depression and suicide/self-injury" and "psychosis and psychotic disorders". The analysis population consists of all randomized participants who received ≥1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
    number (not applicable)
        Depression and suicide/self-injury
    4.1
    6.6
        Psychosis and psychotic disorders
    0.3
    1.1
    Statistical analysis title
    		 % analysis of neuropsychiatric AEs in participants
    Statistical analysis description
    Psychosis and psychotic disorders difference
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 other [15]
    P-value
    		 < 0.001 [16]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Difference in percentages
    Point estimate
    -0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 0.5
    Notes
    [15] - Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. 95% CIs were calculated using the Miettinen and Nurminen method.
    [16] - 2-sided P-value
    Statistical analysis title
    		 % analysis of neuropsychiatric AEs in participants
    Statistical analysis description
    Depression and suicide/self-injury difference
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    728
    Analysis specification
    Pre-specified
    Analysis type
    		 other [17]
    P-value
    		 < 0.001 [18]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Difference in percentages
    Point estimate
    -2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.9
         upper limit
    		 0.8
    Notes
    [17] - Superiority was declared when the 1-sided p-value comparing treatment difference was <0.02497. 95% CIs were calculated using the Miettinen and Nurminen method.
    [18] - 2-sided P-value

    Secondary: Change from baseline in fasting LDL-C at Week 48

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    End point title
    		 Change from baseline in fasting LDL-C at Week 48
    End point description
    The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant-initiated lipid-modifying therapy. The analysis population consists of all randomized participants who had baseline LDL-C data available as well as ≥1 LDL-C measurement after initiating study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    330
    305
    Units: Percent Change from Baseline
        arithmetic mean (confidence interval 95%)
    -1.58 (-3.98 to 0.81)
    8.74 (5.86 to 11.62)
    Statistical analysis title
    		 % change from baseline in LDL-C
    Statistical analysis description
    95% CIs and 2-sided p-values for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    635
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    -10.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.53
         upper limit
    		 -6.49

    Secondary: Change from baseline in fasting non-HDL-C at Week 48

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    End point title
    		 Change from baseline in fasting non-HDL-C at Week 48
    End point description
    The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. The analysis population consists of all randomized participants who had baseline non-HDL-C data available as well as ≥1 non-HDL-C measurement after initiating study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    333
    314
    Units: Percent Change from Baseline
        arithmetic mean (confidence interval 95%)
    -3.83 (-6.27 to -1.40)
    13.26 (10.07 to 16.45)
    Statistical analysis title
    		 % change from baseline in non-HDL-C
    Statistical analysis description
    95% CIs and 2-sided p-values for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    -17.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.89
         upper limit
    		 -13.16

    Secondary: Change from baseline in fasting cholesterol at Week 48

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    End point title
    		 Change from baseline in fasting cholesterol at Week 48
    End point description
    The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant-initiated lipid-modifying therapy. The analysis population consists of all randomized participants who had baseline cholesterol data available as well as ≥1 cholesterol measurement after initiating study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    333
    314
    Units: Percent Change from Baseline
        arithmetic mean (confidence interval 95%)
    -1.97 (-4.74 to 0.79)
    21.77 (18.35 to 25.18)
    Statistical analysis title
    		 % change from baseline in fasting cholesterol
    Statistical analysis description
    95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    -23.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.57
         upper limit
    		 -19.32

    Secondary: Change from baseline in fasting triglycerides at Week 48

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    End point title
    		 Change from baseline in fasting triglycerides at Week 48
    End point description
    The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. The analysis population consists of all randomized participants who had baseline triglyceride data available as well as ≥1 triglyceride measurement after initiating study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    333
    314
    Units: Percent Change from Baseline
        arithmetic mean (confidence interval 95%)
    -12.40 (-19.66 to -5.15)
    22.01 (11.68 to 32.34)
    Statistical analysis title
    		 % change from baseline in fasting triglycerides
    Statistical analysis description
    95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    -35.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -47.1
         upper limit
    		 -24.82

    Secondary: Change from baseline in fasting HDL-C at Week 48

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    End point title
    		 Change from baseline in fasting HDL-C at Week 48
    End point description
    The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant-initiated lipid-modifying therapy. The analysis population consists of all randomized participants who had baseline HDL-C data available as well as ≥1 HDL-C measurement after initiating study treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    333
    314
    Units: Percent Change from Baseline
        arithmetic mean (confidence interval 95%)
    1.86 (0.83 to 2.89)
    8.51 (7.32 to 9.69)
    Statistical analysis title
    		 % change from baseline in fasting HDL-C
    Statistical analysis description
    95% CIs for treatment difference were calculated from an ANCOVA model with terms for baseline lipid level and treatment.
    Comparison groups
    MK-1439A (DOR/3TC/TDF from Day 1) v ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in mean %change from baseline
    Point estimate
    -6.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.97
         upper limit
    		 -4.96

    Secondary: Percentage of participants with HIV-1 RNA below the limit of quantification (BLoQ) at Week 48

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    End point title
    		 Percentage of participants with HIV-1 RNA below the limit of quantification (BLoQ) at Week 48
    End point description
    The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed. The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
        number (not applicable)
    59.6
    55.5
    No statistical analyses for this end point

    Secondary: Plasma concentration of doravirine at Week 48

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    End point title
    		 Plasma concentration of doravirine at Week 48 [19]
    End point description
    Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose. The analysis population consists of all randomized participants in the MK-1439A arm who received ≥1 dose of study drug and had doravirine concentration data available.
    End point type
    Secondary
    End point timeframe
    0 hours post-dose and 2 hours post-dose on Week 48
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: plasma concentrations from this trial were included in this population PK analysis of pooled phase data.
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1)
    Number of subjects analysed
    312
    Units: nM
    arithmetic mean (standard deviation)
        Pre-dose
    1290 ( 799 )
        0.5 to 2 hours post-dose
    2330 ( 1230 )
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA BLoQ at Week 96

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    End point title
    		 Percentage of participants with HIV-1 RNA BLoQ at Week 96
    End point description
    The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 were determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed. The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 MK-1439A (DOR/3TC/TDF from Day 1) ATRIPLA™ (Switch from EFV/FTC/TDF at Week 96)
    Number of subjects analysed
    364
    364
    Units: Percentage of Participants
        number (not applicable)
    59.3
    59.1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 96 weeks
    Adverse event reporting additional description
    All cause-mortality: all allocated participants. Serious and non-serious AEs: all allocated participants who received ≥1 dose of study treatment. Per protocol, non-serious adverse event data were not collected during Study Extensions 2 and 3.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    DOR/3TC/TDF Only (from Day 1) at Base Study
    Reporting group description
    		 Treatment-naive participants took a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for a total of 96 weeks.

    Reporting group title
    DOR/3TC/TDF Switch at Week 96 Base Study
    Reporting group description
    		 Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 48 weeks (and will take ATRIPLA for an additional 48 weeks for a total of 96 weeks).

    Reporting group title
    DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 1
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 96 - Week 192)

    Reporting group title
    DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 1
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 96 - Week 192)

    Reporting group title
    DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 2
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 192 - Week 288)

    Reporting group title
    DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 2
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 192 - Week 288)

    Reporting group title
    DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 3
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 388 - Week 384)

    Reporting group title
    DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 3
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 388 - Week 384)

    Serious adverse events
    		 DOR/3TC/TDF Only (from Day 1) at Base Study DOR/3TC/TDF Switch at Week 96 Base Study DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 1 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 1 DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 2 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 2 DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 3 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 364 (6.04%)
    30 / 364 (8.24%)
    19 / 291 (6.53%)
    12 / 269 (4.46%)
    8 / 192 (4.17%)
    9 / 173 (5.20%)
    2 / 121 (1.65%)
    7 / 111 (6.31%)
         number of deaths (all causes)
    1
    4
    2
    0
    2
    2
    0
    0
         number of deaths resulting from adverse events
    0
    2
    1
    0
    0
    2
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal squamous cell carcinoma
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Anogenital warts
         subjects affected / exposed
    2 / 364 (0.55%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 364 (0.00%)
    2 / 364 (0.55%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    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
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurofibroma
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Leiomyosarcoma metastatic
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    1 / 121 (0.83%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaplastic large-cell lymphoma
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Malignant hypertension
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    1 / 121 (0.83%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 364 (0.27%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    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
    Ectopic pregnancy
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Pyrexia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inflammation
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Insomnia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Nightmare
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Suicide attempt
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
    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
    Schizophrenia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    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
    Subdural haematoma
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Accidental overdose
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    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
    Acetabulum fracture
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    2 / 291 (0.69%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral injury
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Poisoning
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Phimosis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Tachycardia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Myocardial infarction
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Myopericarditis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Syncope
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    Blood and lymphatic system disorders
    Normocytic anaemia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Anaemia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal obstruction
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Pancreatitis acute
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Proctitis ulcerative
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis ulcerative
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholangitis
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholecystitis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    1 / 121 (0.83%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Lipodystrophy acquired
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    1 / 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
    Psoriasis
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    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
    Rash maculo-papular
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash macular
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    2 / 269 (0.74%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    Mania
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid cyst
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic nodular goitre
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vertebral foraminal stenosis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal infection
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Abscess limb
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    Appendicitis
         subjects affected / exposed
    1 / 364 (0.27%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Clostridium difficile infection
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    1 / 364 (0.27%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    1 / 364 (0.27%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine infection
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis bacterial
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Oophoritis
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral bacterial infection
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal disease
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 364 (0.55%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 364 (0.27%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    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
    Anal abscess
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    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
    Diarrhoea infectious
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis mumps
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    1 / 269 (0.37%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute hepatitis C
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    1 / 192 (0.52%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurosyphilis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    1 / 173 (0.58%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    2 / 111 (1.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    1 / 111 (0.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 364 (0.00%)
    0 / 364 (0.00%)
    1 / 291 (0.34%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 364 (0.00%)
    1 / 364 (0.27%)
    0 / 291 (0.00%)
    0 / 269 (0.00%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DOR/3TC/TDF Only (from Day 1) at Base Study DOR/3TC/TDF Switch at Week 96 Base Study DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 1 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 1 DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 2 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 2 DOR/3TC/TDF Only (DOR/3TC/TDF from Day 1) Ext 3 DOR/3TC/TDF Switch (Switch from EFV/FTC/TDF at Week 96) Ext 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    231 / 364 (63.46%)
    281 / 364 (77.20%)
    111 / 291 (38.14%)
    110 / 269 (40.89%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    37 / 364 (10.16%)
    139 / 364 (38.19%)
    2 / 291 (0.69%)
    4 / 269 (1.49%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    47
    155
    2
    4
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    58 / 364 (15.93%)
    56 / 364 (15.38%)
    18 / 291 (6.19%)
    16 / 269 (5.95%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    96
    77
    19
    21
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    13 / 364 (3.57%)
    28 / 364 (7.69%)
    2 / 291 (0.69%)
    2 / 269 (0.74%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    13
    28
    2
    2
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    22 / 364 (6.04%)
    24 / 364 (6.59%)
    4 / 291 (1.37%)
    5 / 269 (1.86%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    25
    26
    4
    5
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    50 / 364 (13.74%)
    58 / 364 (15.93%)
    16 / 291 (5.50%)
    17 / 269 (6.32%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    73
    68
    21
    18
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    31 / 364 (8.52%)
    42 / 364 (11.54%)
    5 / 291 (1.72%)
    7 / 269 (2.60%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    35
    55
    5
    8
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    19 / 364 (5.22%)
    29 / 364 (7.97%)
    1 / 291 (0.34%)
    4 / 269 (1.49%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    23
    42
    3
    4
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    22 / 364 (6.04%)
    20 / 364 (5.49%)
    8 / 291 (2.75%)
    11 / 269 (4.09%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    25
    24
    8
    12
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    20 / 364 (5.49%)
    50 / 364 (13.74%)
    8 / 291 (2.75%)
    5 / 269 (1.86%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    22
    54
    9
    5
    0
    0
    0
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    18 / 364 (4.95%)
    44 / 364 (12.09%)
    0 / 291 (0.00%)
    2 / 269 (0.74%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    20
    49
    0
    2
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    24 / 364 (6.59%)
    38 / 364 (10.44%)
    6 / 291 (2.06%)
    10 / 269 (3.72%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    35
    42
    7
    10
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    18 / 364 (4.95%)
    19 / 364 (5.22%)
    7 / 291 (2.41%)
    14 / 269 (5.20%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    23
    21
    7
    15
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    50 / 364 (13.74%)
    43 / 364 (11.81%)
    40 / 291 (13.75%)
    26 / 269 (9.67%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    89
    61
    58
    36
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    41 / 364 (11.26%)
    30 / 364 (8.24%)
    21 / 291 (7.22%)
    19 / 269 (7.06%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    55
    40
    33
    22
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    30 / 364 (8.24%)
    20 / 364 (5.49%)
    13 / 291 (4.47%)
    11 / 269 (4.09%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    39
    27
    16
    18
    0
    0
    0
    0
    Syphilis
         subjects affected / exposed
    18 / 364 (4.95%)
    14 / 364 (3.85%)
    16 / 291 (5.50%)
    15 / 269 (5.58%)
    0 / 192 (0.00%)
    0 / 173 (0.00%)
    0 / 121 (0.00%)
    0 / 111 (0.00%)
         occurrences all number
    21
    15
    18
    17
    0
    0
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 May 2015
    AM1: Instructions to the Inclusion Criteria were added to direct investigators to provide appropriate guidance to subjects about the use of contraceptives after study completion. Modified Exclusion Criterion added to include the mutations D67N and K70R to those mutations indicative of resistance to emtricitabine, lamivudine, and tenofovir.
    03 Jun 2015
    AM2: Exploratory objective pharmacokinetics/pharmacodynamics changed to a secondary objective. Included updated list of medications prohibited during the use of ATRIPLA (EFV/FTC/TDF), and specified additional visits for the collection of plasma for potential viral resistance testing. Inclusion and Exclusion criteria added to include baseline hemoglobin threshold, and exclusion of subjects with severe hepatic impairment.
    03 Aug 2015
    AM3: Added text to explain the rationale for the selected doses of the lamivudine and TDF components of MK-1439A and include text to disallow concomitant use of interferon. Also clarified that sites would receive the calculated creatinine clearance in the laboratory reports from the central laboratory.
    28 Nov 2016
    AM4: Added open-label study extension 1 for 2 years to collect long-term efficacy and safety data. Clarified visits during which plasma samples were tested for resistance, and removed rosuvastatin as prohibited medication due to an interaction with DOR. Specified that concomitant medications prohibited due to interactions with EFV/FTC/TDF in the base study were allowed in the study extension.
    05 Feb 2019
    AM5: Added open-label study extension 2 to provide continued access to MK-1439A until the drug is available locally in countries participating in the trial or for an additional 2 years (whichever comes first). Added oxcarbazepine and rifapentine as prohibited medications/therapy due to interaction with MK-1439. Clarified that evaluation of Immune Reconstruction Syndrome (IRIS) causality applies only during the base study.

    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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