Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III Multicenter, Open-Label, Randomized Study to Evaluate a Switch to MK-1439A in HIV-1-Infected Subjects Virologically Suppressed on a Regimen of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

    Summary
    EudraCT number
    		 2014-005550-18
    Trial protocol
    		 DE   AT   DK   BE   IT   ES   FR   PL  
    Global end of trial date
    05 Sep 2023

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1439a-024
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02397096
    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
    05 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Feb 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.
    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
    09 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
    Argentina: 21
    Country: Number of subjects enrolled
    Australia: 17
    Country: Number of subjects enrolled
    Austria: 23
    Country: Number of subjects enrolled
    Belgium: 19
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Colombia: 6
    Country: Number of subjects enrolled
    Denmark: 22
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Germany: 58
    Country: Number of subjects enrolled
    Guatemala: 10
    Country: Number of subjects enrolled
    Israel: 16
    Country: Number of subjects enrolled
    Italy: 64
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 9
    Country: Number of subjects enrolled
    Mexico: 30
    Country: Number of subjects enrolled
    New Zealand: 6
    Country: Number of subjects enrolled
    Peru: 7
    Country: Number of subjects enrolled
    Poland: 29
    Country: Number of subjects enrolled
    Russian Federation: 43
    Country: Number of subjects enrolled
    Spain: 33
    Country: Number of subjects enrolled
    Switzerland: 22
    Country: Number of subjects enrolled
    United Kingdom: 51
    Country: Number of subjects enrolled
    United States: 142
    Worldwide total number of subjects
    673
    EEA total number of subjects
    274
    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)
    655
    From 65 to 84 years
    18
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The base study and study extension 1 were conducted at 122 centers in 23 countries. Study extension 2 was conducted at 110 centers in 23 countries. Study extension 3 was at 28 centers in 10 countries.

    Pre-assignment
    Screening details
    		 Out of 852 participants screened, 673 were randomized to study treatment, and 670 were treated.

    Period 1
    Period 1 title
    Day 1 to Week 24
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch Group (ISG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor
    Investigational medicinal product code
    Other name
    Baseline regimen of atazanavir, darunavir, or lopinavir administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule or oral suspension

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule or oral suspension

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule or oral solution

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    tablet

    Arm title
    		 Delayed Switch Group (DSG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor
    Investigational medicinal product code
    Other name
    Baseline regimen of atazanavir, darunavir, or lopinavir administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule or oral suspension

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule or oral suspension

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular
    Pharmaceutical forms
    Tablet, Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    tablet, capsule, or oral suspension

    Investigational medicinal product name
    Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular
    Investigational medicinal product code
    Other name
    Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    tablet

    Number of subjects in period 1
    		Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Started
    450
    223
    Treated
    447
    223
    Completed
    427
    209
    Not completed
    23
    14
         Adverse event, serious fatal
    1
    -
         Physician decision
    2
    3
         Consent withdrawn by subject
    6
    1
         Adverse event, non-fatal
    7
    1
         Lost to follow-up
    3
    4
         Randomized, not treated
    3
    -
         Protocol deviation
    1
    4
         Lack of efficacy
    -
    1
    Period 2
    Period 2 title
    Week 24 to Week 48
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch Group (ISG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Arm title
    		 Delayed Switch Group (DSG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Number of subjects in period 2
    		Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Started
    427
    209
    Completed
    407
    202
    Not completed
    20
    7
         Physician decision
    2
    1
         Consent withdrawn by subject
    5
    2
         Adverse event, non-fatal
    6
    2
         Non-Compliance With Study Drug
    -
    1
         Lost to follow-up
    2
    -
         Lack of efficacy
    5
    1
    Period 3
    Period 3 title
    Study Extension 1
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch Group (ISG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Arm title
    		 Delayed Switch Group (DSG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Number of subjects in period 3 [1]
    		Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Started
    398
    202
    Completed
    357
    179
    Not completed
    41
    23
         Adverse event, serious fatal
    1
    -
         Physician decision
    4
    2
         Consent withdrawn by subject
    21
    7
         Adverse event, non-fatal
    7
    5
         Non-Compliance With Study Drug
    3
    -
         Pregnancy
    1
    -
         Lost to follow-up
    2
    3
         Lack of efficacy
    2
    5
         Protocol deviation
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Number started refers only to participants completing Base Study and volunteering to continue to Study Extension Part 1.
    Period 4
    Period 4 title
    Study Extension 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch Group (ISG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Arm title
    		 Delayed Switch Group (DSG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Number of subjects in period 4 [2]
    		Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Started
    303
    154
    Completed
    129
    78
    Not completed
    174
    76
         Availability of study medication locally
    152
    64
         Adverse event, serious fatal
    2
    -
         Physician decision
    2
    5
         Consent withdrawn by subject
    10
    3
         Adverse event, non-fatal
    3
    3
         Non-Compliance With Study Drug
    1
    -
         Pregnancy
    1
    -
         Lost to follow-up
    2
    1
         Lack of efficacy
    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: Number started refers only to participants completing Base Study, Study Extension Part 1, and volunteering to continue to Study Extension Part 2.
    Period 5
    Period 5 title
    Study Extension 3
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch Group (ISG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Arm title
    		 Delayed Switch Group (DSG)
    Arm description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine/Lamivudine/Tenofovir
    Investigational medicinal product code
    Other name
    Doravirine (PIFELTRO™) Doravirine/Lamivudine/Tenofovir disoproxil fumarate (DELSTRIGO™) MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg

    Number of subjects in period 5 [3]
    		Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Started
    84
    43
    Completed
    69
    39
    Not completed
    15
    4
         Availability of study medication locally
    11
    3
         Consent withdrawn by subject
    2
    1
         Adverse event, non-fatal
    1
    -
         Lost to follow-up
    1
    -
    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: Number started refers only to participants completing Base Study, Study Extension Part 1, Study Extension Part 2 and volunteering to continue to Study Extension Part 3.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG) Total
    Number of subjects
    		 450 223 673
    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)
    		 441 214 655
        From 65-84 years
    		 9 9 18
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 43.1 ( 10.1 ) 43.7 ( 10.6 ) -
    Sex: Female, Male
    Units:
        Female
    		 75 29 104
        Male
    		 375 194 569
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 5 2 7
        Asian
    		 17 8 25
        Native Hawaiian or Other Pacific Islander
    		 1 0 1
        Black or African American
    		 56 34 90
        White
    		 346 168 514
        More than one race
    		 25 11 36
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 98 43 141
        Not Hispanic or Latino
    		 347 177 524
        Unknown or Not Reported
    		 5 3 8

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.
    Reporting group title
    Immediate Switch Group (ISG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    Delayed Switch Group (DSG)
    Reporting group description
    		 Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Subject analysis set title
    Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Subject analysis set title
    Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Subject analysis set title
    Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will switch on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Subject analysis set title
    Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants receiving continuous antiretroviral therapy with a ritonavir-boosted, PI-based regimen for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Primary: Percentage of Participants Maintaining Human Immunodeficiency Virus–1 Ribonucleic Acid (HIV-1 RNA) <40 Copies/mL

    		 Close Top of page
    End point title
    		 Percentage of Participants Maintaining Human Immunodeficiency Virus–1 Ribonucleic Acid (HIV-1 RNA) <40 Copies/mL
    End point description
    The percentage of participants in each arm achieving HIV-1 RNA levels <40 copies/mL 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 and all missing data were considered treatment failures, regardless of the reason. The analysis population consisted of all randomized participants who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    89.7
    93.3
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -3.556
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.977
         upper limit
    		 0.864

    Secondary: Mean Change from Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)
    End point description
    To evaluate the effect on fasting LDL-C of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based regimen, as measured by mean change from baseline in each treatment group. 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 consisted of all randomized participants in the ritonavir-boosted PI-based regimen who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    		 Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Number of subjects analysed
    256
    125
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline
    108.82 ( 34.21 )
    109.00 ( 33.58 )
        Change from Baseline
    -16.54 ( 23.10 )
    -1.94 ( 25.74 )
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) v Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Number of subjects included in analysis
    381
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Treatment Difference
    Point estimate
    -14.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.92
         upper limit
    		 -10.38

    Secondary: Mean Change from Baseline in Fasting Non-high-density Lipoprotein Cholesterol (non-HDL-C)

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in Fasting Non-high-density Lipoprotein Cholesterol (non-HDL-C)
    End point description
    Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid lowering therapy. The analysis population consisted of all randomized participants in the ritonavir-boosted PI-based regimen who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    		 Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Number of subjects analysed
    266
    133
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline
    139.14 ( 42.12 )
    137.99 ( 38.46 )
        Change from Baseline
    -24.74 ( 29.26 )
    -1.31 ( 28.45 )
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch (Ritonavir--boosted, PI-based) Group (ISG) v Delayed Switch (Ritonavir-boosted, PI-based) Group (DSG)
    Number of subjects included in analysis
    399
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Treatment Difference
    Point estimate
    -23.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28
         upper limit
    		 -18.05

    Secondary: Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL

    		 Close Top of page
    End point title
    		 Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL
    End point description
    The percentage of participants in each arm achieving HIV-1 RNA levels <50 copies/mL 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 and all missing data were considered treatment failures, regardless of the reason. The analysis population consisted of all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    93.7
    94.6
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.877
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.706
         upper limit
    		 2.952
    Notes
    [1] - DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -8 percentage points.

    Secondary: Mean Change from Baseline in Cluster of Differentiation (CD4) Cell Counts

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in Cluster of Differentiation (CD4) Cell Counts
    End point description
    The mean change from baseline in CD4 cell counts was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued due to lack of efficacy. Cell counts were measured and expressed as cells/mm^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay. The analysis population consisted of all randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
    End point type
    Secondary
    End point timeframe
    Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    402
    209
    Units: cells/mm^3
    arithmetic mean (standard deviation)
        Baseline
    660.5 ( 293.4 )
    655.6 ( 279.3 )
        Change from Baseline
    13.9 ( 168.1 )
    18.0 ( 157.7 )
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    611
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.6
         upper limit
    		 23.5

    Secondary: Mean Change from Baseline in Cluster of Differentiation (CD4) Cell Counts up to Week 24

    		 Close Top of page
    End point title
    		 Mean Change from Baseline in Cluster of Differentiation (CD4) Cell Counts up to Week 24
    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 due to lack of efficacy. Cell counts were measured and expressed as cells/mm^3, and percent change was then calculated. CD4 cell counts were quantified by a central laboratory using a commercially available assay. The analysis population consisted of all randomized participants who received at least 1 dose of study drug and had a measurement at baseline and had at least one post baseline time point assessed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    412
    209
    Units: cells/mm^3
    geometric mean (standard deviation)
        Baseline
    664.5 ( 300.7 )
    655.6 ( 279.3 )
        Change from Baseline
    5.1 ( 174.9 )
    18.0 ( 157.7 )
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    621
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -12.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.1
         upper limit
    		 15.4

    Secondary: Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL up to Week 24

    		 Close Top of page
    End point title
    		 Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL up to Week 24
    End point description
    To evaluate the immunological effect of an immediate switch to MK -1439A on Study Day 1 compared with continuation of a ritonavir boosted, PI-based regimen, as measured by the proportion of subjects maintaining HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay (<40 copies/mL) in both treatment groups. The analysis population consisted of all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    92.8
    93.3
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.427
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.591
         upper limit
    		 3.738

    Secondary: Percentage of Participants with HIV-1 RNA >=50 Copies/mL

    		 Close Top of page
    End point title
    		 Percentage of Participants with HIV-1 RNA >=50 Copies/mL
    End point description
    The percentage of participants in each arm achieving HIV-1 RNA levels >=50 copies/mL 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. The analysis population consisted of all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    1.6
    1.8
    Statistical analysis title
    		 ISG, DSG
    Comparison groups
    Immediate Switch Group (ISG) v Delayed Switch Group (DSG)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -0.232
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.529
         upper limit
    		 2.064
    Notes
    [2] - DOR/3TC/TDF QD ISG is concluded to be non-inferior to baseline regimen DSG if the lower bound of the 95% CI for the difference in percent response is above -4 percentage points.

    Secondary: Percentage of Participants Experiencing ≥1 Adverse Event (AE)

    		 Close Top of page
    End point title
    		 Percentage of Participants Experiencing ≥1 Adverse Event (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 at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    68.9
    52.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)

    		 Close Top of page
    End point title
    		 Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)
    End point description
    A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed. The analysis population consisted of all randomized participants who received at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to 24 weeks
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    2.9
    3.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants Discontinuing From Study Medication Due to an AE(s)

    		 Close Top of page
    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 at least 1 dose of study drug.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    		 Immediate Switch Group (ISG) Delayed Switch Group (DSG)
    Number of subjects analysed
    447
    223
    Units: Percentage of Participants
        number (not applicable)
    2.5
    0.4
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to ~338 weeks
    Adverse event reporting additional description
    All cause-mortality was reported on all allocated participants. Serious and non-serious AEs were reported for all allocated participants who received ≥1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    ISG Base Study Weeks 0-24
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    ISG Base Study Weeks 24-48
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    DSG Base Study Weeks 24-48
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    DSG Base Study Weeks 0-24
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    ISG Study Extension 1
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    DSG Study Extension 2
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    DSG Study Extension 1
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    ISG Study Extension 2
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    ISG Study Extension 3
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 (nuceloside/nucleotide reverse transcriptase inhibitors) NRTIs for >=6 months with undetectable HIV-1 RNA switched on Day 1 to MK-1439A single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Reporting group title
    DSG Study Extension 3
    Reporting group description
    		 Participants received continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for >=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they switched to MK-1439A single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions.

    Serious adverse events
    		 ISG Base Study Weeks 0-24 ISG Base Study Weeks 24-48 DSG Base Study Weeks 24-48 DSG Base Study Weeks 0-24 ISG Study Extension 1 DSG Study Extension 2 DSG Study Extension 1 ISG Study Extension 2 ISG Study Extension 3 DSG Study Extension 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 447 (2.91%)
    11 / 427 (2.58%)
    4 / 209 (1.91%)
    8 / 223 (3.59%)
    37 / 398 (9.30%)
    7 / 154 (4.55%)
    13 / 202 (6.44%)
    13 / 303 (4.29%)
    3 / 84 (3.57%)
    1 / 43 (2.33%)
         number of deaths (all causes)
    1
    0
    0
    0
    1
    0
    0
    3
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    3 / 398 (0.75%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    1 / 84 (1.19%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Burkitt's lymphoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epstein-Barr virus associated lymphoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Laryngeal cancer
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Vascular disorders
    Ischaemia
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shock haemorrhagic
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    2 / 398 (0.50%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    2 / 398 (0.50%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Obstructive sleep apnoea syndrome
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    1 / 209 (0.48%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Behaviour disorder
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 447 (0.22%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Amylase increased
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 447 (0.22%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 447 (0.22%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CD4 lymphocytes decreased
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 447 (0.22%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    1 / 209 (0.48%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amyotrophic lateral sclerosis
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Distal intestinal obstruction syndrome
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal ulcer haemorrhage
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Prerenal failure
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    1 / 84 (1.19%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    1 / 209 (0.48%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    2 / 398 (0.50%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 4
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    2 / 398 (0.50%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    1 / 209 (0.48%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    2 / 202 (0.99%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    1 / 84 (1.19%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    1 / 154 (0.65%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphangitis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle abscess
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 447 (0.22%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    3 / 223 (1.35%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    2 / 202 (0.99%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    0 / 0
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    1 / 303 (0.33%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Shigella infection
         subjects affected / exposed
    0 / 447 (0.00%)
    1 / 427 (0.23%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syphilis
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    1 / 202 (0.50%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tuberculous pleurisy
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    1 / 223 (0.45%)
    0 / 398 (0.00%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    1 / 398 (0.25%)
    0 / 154 (0.00%)
    0 / 202 (0.00%)
    0 / 303 (0.00%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 ISG Base Study Weeks 0-24 ISG Base Study Weeks 24-48 DSG Base Study Weeks 24-48 DSG Base Study Weeks 0-24 ISG Study Extension 1 DSG Study Extension 2 DSG Study Extension 1 ISG Study Extension 2 ISG Study Extension 3 DSG Study Extension 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    100 / 447 (22.37%)
    63 / 427 (14.75%)
    33 / 209 (15.79%)
    28 / 223 (12.56%)
    107 / 398 (26.88%)
    11 / 154 (7.14%)
    57 / 202 (28.22%)
    24 / 303 (7.92%)
    9 / 84 (10.71%)
    3 / 43 (6.98%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    29 / 447 (6.49%)
    11 / 427 (2.58%)
    14 / 209 (6.70%)
    5 / 223 (2.24%)
    22 / 398 (5.53%)
    3 / 154 (1.95%)
    13 / 202 (6.44%)
    2 / 303 (0.66%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    32
    11
    14
    5
    24
    5
    16
    3
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    20 / 447 (4.47%)
    13 / 427 (3.04%)
    9 / 209 (4.31%)
    5 / 223 (2.24%)
    18 / 398 (4.52%)
    0 / 154 (0.00%)
    11 / 202 (5.45%)
    3 / 303 (0.99%)
    1 / 84 (1.19%)
    0 / 43 (0.00%)
         occurrences all number
    21
    13
    10
    5
    20
    0
    14
    3
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 447 (3.13%)
    8 / 427 (1.87%)
    3 / 209 (1.44%)
    5 / 223 (2.24%)
    21 / 398 (5.28%)
    1 / 154 (0.65%)
    4 / 202 (1.98%)
    5 / 303 (1.65%)
    1 / 84 (1.19%)
    0 / 43 (0.00%)
         occurrences all number
    14
    9
    5
    5
    23
    1
    4
    5
    1
    0
    Back pain
         subjects affected / exposed
    9 / 447 (2.01%)
    16 / 427 (3.75%)
    1 / 209 (0.48%)
    4 / 223 (1.79%)
    21 / 398 (5.28%)
    2 / 154 (1.30%)
    9 / 202 (4.46%)
    7 / 303 (2.31%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    9
    16
    1
    4
    22
    2
    11
    7
    0
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 447 (0.00%)
    0 / 427 (0.00%)
    0 / 209 (0.00%)
    0 / 223 (0.00%)
    0 / 398 (0.00%)
    6 / 154 (3.90%)
    0 / 202 (0.00%)
    4 / 303 (1.32%)
    7 / 84 (8.33%)
    3 / 43 (6.98%)
         occurrences all number
    0
    0
    0
    0
    0
    6
    0
    4
    7
    3
    Nasopharyngitis
         subjects affected / exposed
    33 / 447 (7.38%)
    19 / 427 (4.45%)
    9 / 209 (4.31%)
    12 / 223 (5.38%)
    51 / 398 (12.81%)
    2 / 154 (1.30%)
    29 / 202 (14.36%)
    5 / 303 (1.65%)
    0 / 84 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    34
    21
    10
    14
    68
    3
    54
    5
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 May 2015
    Amendment 1 was implemented to modify exclusion criterion #4b to include the mutations D67N and K70R in the list of excluded mutations as these 2 mutations confer decreased susceptibility to NRTIs and to clarify single mutations or components of double or triple mutations in the DOR resistance mutation list.
    03 Jun 2015
    Amendment 2 was implemented to change the PK/PD evaluation from an exploratory objective to a secondary objective given its importance in supporting the assessment of the exposure-response relationship for safety and efficacy in long-term use of DOR/3TC/TDF.
    12 Aug 2015
    Amendment 3 was implemented to add text to explain the rationale for the selected doses of the lamivudine and TDF components of DOR/3TC/TDF.
    10 Dec 2015
    Amendment 4 was implemented to add a secondary objective to evaluate the antiretroviral activity of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with continuation of a ritonavir-boosted PI based-regimen for 24 weeks, as measured by the proportion of participants with HIV-1 RNA ≥50 copies/mL (ie, viral rebound) at Study Week 48 in the ISG and at Study Week 24 in the DSG based on the FDA snapshot approach.
    06 May 2016
    Amendment 5 was implemented to add open-label study extension 1 for 2 years to collect long-term efficacy and safety data.
    01 Aug 2016
    Amendment 6 was implemented to expand subject population by allowing enrollment of participants on InSTIs (specifically, EVG) and NNRTIs (specifically, EFV, NVP, or RPV) and use of cobicistat as a booster for PIs in order to better reflect the real-world use of various antiretroviral agents and current HIV treatment guidelines.
    06 Mar 2018
    Amendment 7 was implemented to add open-label study extension 2 to provide continued access to DOR/3TC/TDF until the drug is available locally in countries participating in the trial or for an additional 2 years (whichever comes first).
    20 Dec 2019
    Amendment 8 was implemented to extend the trial to (1) provide continued access to MK-1439A for participants who are deriving benefit from MK-1439A until the drug is available locally in countries participating in the trial or for an additional 2 years (whichever comes first), and (2) collect key safety information from participants who continue on MK-1439A.
    06 Dec 2022
    Amendment 10 was implemented as a country-specific amendment for Guatemala, Mexico, Peru, Australia, New Zealand, Russia, and Spain to inform regarding the Sponsor’s name and address change and updates that were made to the Code of Conduct in the previous amendment.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 02 21:12:38 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA