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    Clinical Trial Results:
    Phase IIb, Double-Blinded, Multicenter, Randomized Study to Assess the Effect on Central Nervous System (CNS) Toxicity of Switching from ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Subjects

    Summary
    EudraCT number
    		 2015-003617-18
    Trial protocol
    		 GB   IE  
    Global end of trial date
    07 Feb 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Feb 2025
    First version publication date
    09 Feb 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-1439A-028
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02652260
    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@msd.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    07 Feb 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Aug 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study aims to evaluate a switch from fixed dose combination (FDC) treatment with ATRIPLA^TM for 12 weeks prior to screening to FDC treatment with Doravirine, Tenofovir, Lamivudine (MK-1439A) in virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA^TM to Doravirine, Tenofovir, Lamivudine results in a lower proportion of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA^TM treatment.
    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
    04 Mar 2016
    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
    Ireland: 2
    Country: Number of subjects enrolled
    South Africa: 45
    Country: Number of subjects enrolled
    United Kingdom: 39
    Worldwide total number of subjects
    86
    EEA total number of subjects
    2
    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)
    82
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of 112 participants screened, 86 were randomized and received study treatment.

    Period 1
    Period 1 title
    Base Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch to MK-1439A
    Arm description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period and 12 weeks during the Open-Label period.

    Investigational medicinal product name
    Placebo to ATRIPLA™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period.

    Investigational medicinal product name
    Placebo to Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period.

    Arm title
    		 Deferred Switch to MK-1439A
    Arm description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    ATRIPLA™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period.

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for 24 weeks during the Open-Label period.

    Number of subjects in period 1
    		Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Started
    43
    43
    Switched Over to MK-1439A
    0 [1]
    42
    Completed
    43
    41
    Not completed
    0
    2
         Consent withdrawn by subject
    -
    1
         Pregnancy
    -
    1
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only participants in the Deferred Switch to MK-1439A arm switched treatments.
    Period 2
    Period 2 title
    Study Extension 1 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch to MK-1439A
    Arm description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for an additional 96 weeks during the Open-Label extension period 1.

    Arm title
    		 Deferred Switch to MK-1439A
    Arm description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for an additional 96 weeks during the Open-Label extension period 1.

    Number of subjects in period 2
    		Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Started
    43
    41
    Completed
    39
    34
    Not completed
    4
    7
         Consent withdrawn by subject
    1
    2
         Availability of study drug locally
    1
    1
         Adverse event, non-fatal
    -
    2
         Pregnancy
    1
    1
         Lack of efficacy
    1
    1
    Period 3
    Period 3 title
    Study Extension 2 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch to MK-1439A
    Arm description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2.

    Arm title
    		 Deferred Switch to MK-1439A
    Arm description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2.

    Number of subjects in period 3 [2]
    		Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Started
    39
    33
    Completed
    17
    19
    Not completed
    22
    14
         Adverse event, non-fatal
    1
    -
         Availability of study drug locally
    18
    13
         Pregnancy
    1
    1
         Non-Compliance with study drug
    1
    -
         Lost to follow-up
    1
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Not all study participants continued into optional study extension 2.
    Period 4
    Period 4 title
    Study Extension 3 (Open-Label)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Immediate Switch to MK-1439A
    Arm description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.

    Arm title
    		 Deferred Switch to MK-1439A
    Arm description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Doravirine, Tenofovir, Lamivudine
    Investigational medicinal product code
    Other name
    MK-1439A
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3

    Number of subjects in period 4
    		Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Started
    17
    19
    Completed
    10
    8
    Not completed
    7
    11
         Physician decision
    7
    10
         Pregnancy
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Immediate Switch to MK-1439A
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).

    Reporting group title
    Deferred Switch to MK-1439A
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).

    Reporting group values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A Total
    Number of subjects
    		 43 43 86
    Age categorical
    Units: Participants
        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)
    		 40 42 82
        From 65-84 years
    		 3 1 4
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 41.8 ( 11.9 ) 41.6 ( 11.2 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 19 17 36
        Male
    		 24 26 50
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 3 1 4
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 25 23 48
        White
    		 12 19 31
        More than one race
    		 3 0 3
        Unknown or Not Reported
    		 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 1 5
        Not Hispanic or Latino
    		 39 42 81
        Unknown or Not Reported
    		 0 0 0
    CNS Toxicity Percentage Of Maximum Score
    Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converting the sum to a percentage of the maximum possible sum of intensities (10 x 3 = 30). A higher CNS score indicates worsening symptoms.
    Units: Percentage of maximum score
        arithmetic mean (standard deviation)
    		 32.9 ( 16.5 ) 37.1 ( 19.0 ) -
    Fasting Lipids - LDL Cholesterol
    Mean concentrations of low-density lipoprotein (LDL) cholesterol. All randomized participants who received at least one dose of study treatment were analyzed.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 98.67 ( 35.28 ) 99.54 ( 33.57 ) -
    Fasting Lipids - Non-HDL Cholesterol
    Mean concentrations of non high-density lipoprotein (HDL) cholesterol. All randomized participants who received at least one dose of study treatment were analyzed
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 118.73 ( 36.93 ) 117.76 ( 37.83 ) -
    Fasting Lipids - Cholesterol
    Mean concentrations of cholesterol. All randomized participants who received at least one dose of study treatment were analyzed.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 178.11 ( 36.39 ) 173.02 ( 36.62 ) -
    Fasting Lipids - HDL Cholesterol
    Mean concentrations of HDL cholesterol. All randomized participants who received at least one dose of study treatment.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 59.38 ( 14.58 ) 55.27 ( 14.00 ) -
    Fasting Lipids - Triglyceride
    Mean concentrations of triglyceride. All randomized participants who received at least one dose of study treatment.
    Units: mg/dL
        arithmetic mean (standard deviation)
    		 107.49 ( 65.64 ) 91.39 ( 39.43 ) -

    End points

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    End points reporting groups
    Reporting group title
    Immediate Switch to MK-1439A
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).

    Reporting group title
    Deferred Switch to MK-1439A
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Reporting group title
    Immediate Switch to MK-1439A
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).

    Reporting group title
    Deferred Switch to MK-1439A
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Reporting group title
    Immediate Switch to MK-1439A
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).

    Reporting group title
    Deferred Switch to MK-1439A
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).
    Reporting group title
    Immediate Switch to MK-1439A
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Eligible participants from Base Study (Day 1 to Week 24) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 24 to 120), Extension 2 (Weeks 120 to 216), and Extension 3 (Weeks 216 to 312).

    Reporting group title
    Deferred Switch to MK-1439A
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks (Day 1 to Week 12), followed by open-label MK-1439A orally, once daily for 24 weeks (Weeks 12 to 36). Eligible participants from Base Study (Day 1 to Week 36) may have entered open-label optional study extensions to receive MK-1439A once daily during Study Extension 1 (Weeks 36 to 132), Extension 2 (Weeks 132 to 228), and Extension 3 (Weeks 228 to 324).

    Subject analysis set title
    Combined Treatment Groups: Time of Switch
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Immediate Switch to MK-1439A: Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Deferred Switch to MK-1439A: Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for 24 weeks.

    Subject analysis set title
    Combined Treatment Groups: Week 24 Post-Switch
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Immediate Switch to MK-1439A: Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Deferred Switch to MK-1439A: Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for 24 weeks.

    Subject analysis set title
    Combined Treatment Groups
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Immediate Switch to MK-1439A: Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Deferred Switch to MK-1439A: Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for 24 weeks.

    Subject analysis set title
    Combined Treatment Groups
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Immediate Switch to MK-1439A: Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded MK-1439A orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for an additional 12 weeks. Deferred Switch to MK-1439A: Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label MK-1439A orally, once daily for 24 weeks.

    Primary: Percentage of participants with at least one central nervous system (CNS) toxicity of at least grade 2 intensity at week 12

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    End point title
    		 Percentage of participants with at least one central nervous system (CNS) toxicity of at least grade 2 intensity at week 12
    End point description
    A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach. All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data were analyzed.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Percentage of participants
        number (not applicable)
    41.9
    37.2
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Statistical analysis description
    The Immediate Switch group will be considered statistically significantly smaller than the Delayed Switch group if the upper bound of the 95% confidence interval for the treatment difference is less than 0.
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.331
    Method
    		 Miettinen and Nurminen
    Parameter type
    		 Estimated Difference
    Point estimate
    4.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.92
         upper limit
    		 24.85

    Secondary: Percentage of participants with at least one CNS toxicity of at least grade 2 intensity at week 4

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    End point title
    		 Percentage of participants with at least one CNS toxicity of at least grade 2 intensity at week 4
    End point description
    A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach. All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data were analyzed.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Percentage of participants
        number (not applicable)
    46.5
    65.1
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Statistical analysis description
    The Immediate Switch group will be considered statistically significantly smaller than the Delayed Switch group if the upper bound of the 95% confidence interval for the treatment difference is less than 0.
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -18.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.14
         upper limit
    		 2.51

    Secondary: Change from baseline in CNS toxicity score at week 4

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    End point title
    		 Change from baseline in CNS toxicity score at week 4
    End point description
    A questionnaire was used to solicit for CNS toxicity based on 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; & abnormal dreams. Participants were asked to rate the intensity of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing all 10 CNS toxicities & converting to a percentage of the maximum possible sum of intensities. A positive change from baseline score = worsening symptoms. A negative change from baseline score = improvement in symptoms. All randomized participants who received ≥1 dose of study treatment & had baseline data where applicable were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 4
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Percentage of maximum score
        arithmetic mean (confidence interval 95%)
    -17.6 (-23.4 to -11.8)
    -15.6 (-22.0 to -9.2)
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.5
         upper limit
    		 6.5

    Secondary: Percentage of participants with at least one CNS toxicity of at least grade 2 intensity at time of switch, and at 24 weeks post-switch for the combined treatment groups

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    End point title
    		 Percentage of participants with at least one CNS toxicity of at least grade 2 intensity at time of switch, and at 24 weeks post-switch for the combined treatment groups
    End point description
    A questionnaire was used to solicit for CNS toxicity based on 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; & abnormal dreams. Participants were asked to rate the intensity for the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. For the Immediate Switch Group (ISG) time of switch was study Day 1, and week 24 post-switch was week 24. For the Delayed Switch Group (DSG) time of switch was study week 12, and week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment & had baseline data when applicable. Per protocol, the combined treatment groups were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (time of switch) and 24 weeks post-switch
    End point values
    		 Combined Treatment Groups: Time of Switch Combined Treatment Groups: Week 24 Post-Switch
    Number of subjects analysed
    86
    86
    Units: Percentage of participants
        number (not applicable)
    68.6
    30.2
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Statistical analysis description
    Change from time of switch to 24 weeks post-switch: Treatment difference in percent response
    Comparison groups
    Combined Treatment Groups: Week 24 Post-Switch v Combined Treatment Groups: Time of Switch
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    Method
    Parameter type
    		 Difference in Percentage
    Point estimate
    -38.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -51.2
         upper limit
    		 -23.8
    Notes
    [1] - The 95% CI was calculated by the method of Miettinen and Nurminen.

    Secondary: Change from baseline in CNS toxicity score at week 12

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    End point title
    		 Change from baseline in CNS toxicity score at week 12
    End point description
    A questionnaire was used to solicit for CNS toxicity based on 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; & abnormal dreams. Participants were asked to rate the intensity of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. The CNS toxicity score was calculated by summing all 10 CNS toxicities & converting to a percentage of the maximum possible sum of intensities. A positive change from baseline score = worsening symptoms. A negative change from baseline score = improvement in symptoms. All randomized participants who received ≥1 dose of study treatment & had baseline data where applicable were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Percentage of maximum score
        arithmetic mean (confidence interval 95%)
    -18.1 (-22.9 to -13.3)
    -21.7 (-27.9 to -15.5)
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    86
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 11.3

    Secondary: Change from baseline in fasting lipids at week 12

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    End point title
    		 Change from baseline in fasting lipids at week 12
    End point description
    Blood was collected under fasting conditions on Day 1 and on week 12 in order to determine the concentration of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride. All randomized participants who received at least one dose of study treatment, and have required lipid data were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (study Day 1) and study week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    37
    41
    Units: mg/dL
    arithmetic mean (standard deviation)
        LDL Cholesterol
    -10.78 ( 15.85 )
    -1.88 ( 14.88 )
        Non-HDL Cholesterol
    -14.08 ( 17.17 )
    -0.37 ( 16.51 )
        Cholesterol
    -22.14 ( 19.49 )
    0.00 ( 18.04 )
        HDL Cholesterol
    -8.05 ( 7.74 )
    0.37 ( 7.91 )
        Triglyceride
    -21.19 ( 43.37 )
    7.10 ( 38.55 )
    Statistical analysis title
    		 Difference Estimate: LDL Cholesterol
    Statistical analysis description
    The 95% CI for treatment difference was calculated from an ANCOVA model with terms for baseline lipid level, use of lipid lowering therapy at study Day 1 and treatment
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference Estimate
    Point estimate
    -9.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.69
         upper limit
    		 -2.35
    Statistical analysis title
    		 Difference Estimate: Non-HDL Cholesterol
    Statistical analysis description
    The 95% CI for treatment difference was calculated from an ANCOVA model with terms for baseline lipid level, use of lipid lowering therapy at study Day 1 and treatment
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference Estimate
    Point estimate
    -13.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.79
         upper limit
    		 -6.35
    Statistical analysis title
    		 Difference Estimate: Triglyceride
    Statistical analysis description
    The 95% CI for treatment difference was calculated from an ANCOVA model with terms for baseline lipid level, use of lipid lowering therapy at study Day 1 and treatment
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference Estimate
    Point estimate
    -22.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.52
         upper limit
    		 -5.84
    Statistical analysis title
    		 Difference Estimate: HDL Cholesterol
    Statistical analysis description
    The 95% CI for treatment difference was calculated from an ANCOVA model with terms for baseline lipid level, use of lipid lowering therapy at study Day 1 and treatment
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference Estimate
    Point estimate
    -8.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.76
         upper limit
    		 -4.6
    Statistical analysis title
    		 Difference Estimate: Cholesterol
    Statistical analysis description
    The 95% CI for treatment difference was calculated from an ANCOVA model with terms for baseline lipid level, use of lipid lowering therapy at study Day 1 and treatment
    Comparison groups
    Immediate Switch to MK-1439A v Deferred Switch to MK-1439A
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Difference Estimate
    Point estimate
    -21.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.63
         upper limit
    		 -13.21

    Secondary: CNS toxicity scores at time of switch, and at 24 weeks post-switch for the combined treatment groups

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    End point title
    		 CNS toxicity scores at time of switch, and at 24 weeks post-switch for the combined treatment groups
    End point description
    A questionnaire was used to solicit for CNS toxicity based on 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; & abnormal dreams. Participants were asked to rate the intensity for the 10 events as none (Grade 0) through severe (Grade 3). The CNS toxicity score was calculated by summing across all 10 CNS toxicities and converted to a percentage of the maximum possible sum of intensities. A higher CNS score = worse symptoms. A positive change in CNS score = worsening symptoms. A negative change = improvement in symptoms. For the ISG time of switch was Day 1, and week 24 post-switch was week 24. For the DSG time of switch was week 12, and week 24 post-switch was week 36. All randomized participants who received ≥1 dose of study treatment & had baseline data where applicable. Per protocol, the combined treatment groups were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (time of switch) and 24 weeks post-switch
    End point values
    		 Combined Treatment Groups: Time of Switch Combined Treatment Groups: Week 24 Post-Switch
    Number of subjects analysed
    86
    86
    Units: Percentage of maximum score
        arithmetic mean (confidence interval 95%)
    24.2 (20.5 to 27.9)
    10.7 (8.7 to 12.8)
    Statistical analysis title
    		 Treatment Difference: Immediate - Delayed Switch
    Statistical analysis description
    Change from time of switch to 24 weeks post-switch: Treatment difference in score
    Comparison groups
    Combined Treatment Groups: Time of Switch v Combined Treatment Groups: Week 24 Post-Switch
    Number of subjects included in analysis
    172
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -13.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.8
         upper limit
    		 -10.1
    Notes
    [2] - The 95% CI was based on a t-distribution.

    Secondary: Change in fasting lipids between time of switch and week 24 post-switch for the combined treatment groups

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    End point title
    		 Change in fasting lipids between time of switch and week 24 post-switch for the combined treatment groups
    End point description
    Blood was collected under fasting conditions at time of switch and 24 weeks post-switch in order to determine the change from baseline of the following lipids: low-density lipoprotein (LDL) cholesterol; Non high-density lipoprotein (HDL) cholesterol; cholesterol; HDL cholesterol; and triglyceride. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment, and have required lipid data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (time of switch) and 24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    76
    Units: mg/dL
    arithmetic mean (standard deviation)
        LDL Cholesterol
    -10.97 ( 17.15 )
        Non-HDL Cholesterol
    -13.18 ( 19.82 )
        Cholesterol
    -20.91 ( 20.19 )
        HDL Cholesterol
    -7.72 ( 9.53 )
        Triglyceride
    -12.99 ( 46.61 )
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA <50 and <40 copies/ml at week 24 post-switch for the combined treatment groups

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    End point title
    		 Percentage of participants with HIV-1 RNA <50 and <40 copies/ml at week 24 post-switch for the combined treatment groups
    End point description
    Blood was collected under fasting conditions at 24 weeks post-switch in order to determine the HIV-1 RNA. For the ISG week 24 post-switch was week 24. For the DSG week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment, and have required HIV-1 RNA data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Percentage of participants
    number (confidence interval 95%)
        < 50 copies/mL
    95.3 (88.4 to 98.7)
        < 40 copies/mL
    95.3 (88.4 to 98.7)
    No statistical analyses for this end point

    Secondary: Change from time of switch to week 24 post switch in CD4 T-cell count for the combined treatment groups

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    End point title
    		 Change from time of switch to week 24 post switch in CD4 T-cell count for the combined treatment groups
    End point description
    Blood was collected at time of switch and at 24 weeks post-switch in order to determine the CD4 T-cell count. For the ISG time of switch was study Day 1, and week 24 post-switch was week 24. For the DSG time of switch was study week 12, and week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment, and have required CD4 T-cell data. Based on the protocol-specified plan, the combined treatment groups was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (time of switch) and 24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    70.4 (35.9 to 104.8)
    No statistical analyses for this end point

    Secondary: Number of participants with one or more drug-related AEs through study week 12

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    End point title
    		 Number of participants with one or more drug-related AEs through study week 12
    End point description
    An adverse event (AE) is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug. All randomized participants who received at least one dose of study treatment were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Participants
    14
    9
    No statistical analyses for this end point

    Secondary: Number of participants with one or more Serious Adverse Events (SAEs) through study week 12

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    End point title
    		 Number of participants with one or more Serious Adverse Events (SAEs) through study week 12
    End point description
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. All randomized participants who received at least one dose of study treatment were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with one or more Adverse Events (AEs) through study week 12

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    End point title
    		 Number of participants with one or more Adverse Events (AEs) through study week 12
    End point description
    An adverse event (AE) is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. All randomized participants who received at least one dose of study treatment were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Participants
    34
    34
    No statistical analyses for this end point

    Secondary: Number of participants with one or more drug-related SAEs through study week 12

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    End point title
    		 Number of participants with one or more drug-related SAEs through study week 12
    End point description
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug. All randomized participants who received at least one dose of study treatment were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued treatment due to an AE through study week 12

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    End point title
    		 Number of participants who discontinued treatment due to an AE through study week 12
    End point description
    An AE is 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. All randomized participants who received at least one dose of study treatment were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to Week 12
    End point values
    		 Immediate Switch to MK-1439A Deferred Switch to MK-1439A
    Number of subjects analysed
    43
    43
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Secondary: Number of participants with one or more drug-related AEs for the combined treatment groups 24 weeks after the switch

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    End point title
    		 Number of participants with one or more drug-related AEs for the combined treatment groups 24 weeks after the switch
    End point description
    An AE was any untoward medical occurrence in a participant administered a pharmaceutical product & which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. A drug-related AE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. All randomized participants who received ≥1 dose of study treatment, & have baseline data for analyses requiring baseline data. Per protocol, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Participants
    18
    No statistical analyses for this end point

    Secondary: Number of participants with one or more AEs for the combined treatment groups 24 weeks after the switch

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    End point title
    		 Number of participants with one or more AEs for the combined treatment groups 24 weeks after the switch
    End point description
    An AE was 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. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol - specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. All randomized participants who received ≥1 dose of study treatment, and have baseline data for analyses requiring baseline data were analyzed. Per protocol, the combined treatment group was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Participants
    71
    No statistical analyses for this end point

    Secondary: Number of participants with one or more drug-related SAEs for the combined treatment groups 24 weeks after the switch

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    End point title
    		 Number of participants with one or more drug-related SAEs for the combined treatment groups 24 weeks after the switch
    End point description
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. A drug-related SAE was determined by the investigator to be related to the drug. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Participants
    0
    No statistical analyses for this end point

    Secondary: Number of participants with one or more SAEs for the combined treatment groups 24 weeks after the switch

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    End point title
    		 Number of participants with one or more SAEs for the combined treatment groups 24 weeks after the switch
    End point description
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that results in any of the following: death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing hospitalization; is a congenital anomaly/birth defect; is another important medical event; is a cancer; is associated with an overdose. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. All randomized participants who received at least one dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Participants
    1
    No statistical analyses for this end point

    Secondary: Number of participants who discontinued treatment due to an AE for the combined treatment groups 24 weeks after the switch

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    End point title
    		 Number of participants who discontinued treatment due to an AE for the combined treatment groups 24 weeks after the switch
    End point description
    An AE was 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. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor’s product, is also an AE. For the ISG 24 week post-switch was week 24; for the DSG week 24 post-switch was week 36. All randomized participants who received ≥1 dose of study treatment, and have baseline data for analyses requiring baseline data. Based on the protocol-specified plan, the combined treatment groups was analyzed. One participant in the DSG who discontinued from the study, before switching to MK-1439A, was not included in the analysis.
    End point type
    Secondary
    End point timeframe
    24 weeks post-switch
    End point values
    		 Combined Treatment Groups
    Number of subjects analysed
    85
    Units: Participants
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 326 weeks
    Adverse event reporting additional description
    All cause-mortality was reported on all allocated participants. AEs were reported for all allocated participants who received ≥1 dose of study treatment. Per protocol, serious adverse events and all-cause mortality were collected up to 326 weeks, and non-serious adverse event data were collected up to 134 weeks.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Immediate Switch Group Day 1 to Week 24
    Reporting group description
    		 Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks

    Reporting group title
    Deferred Switch Group Double-blind Day 1 to Week 12
    Reporting group description
    		 Participants continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks.

    Reporting group title
    Deferred Switch Group Open-label Week 12-36
    Reporting group description
    		 Participants who continued their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks switched to open-label doravirine, tenofovir, lamivudine orally, once daily for a total of 24 weeks (Week 12 - Week 36).

    Reporting group title
    Immediate Switch Group only (Week 24-120) EXT 1
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 24 - Week 120)

    Reporting group title
    Deferred Switch Group (Week 36-132) EXT 1
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 36 - Week 132)

    Reporting group title
    Deferred Switch Group (Week 132-228) EXT 2
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 132 - Week 228)

    Reporting group title
    Immediate Switch Group (Week 120-216) EXT 2
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 120 - Week 216)

    Reporting group title
    Immediate Switch Group (Week 216-312) EXT 3
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 216 - Week 312)

    Reporting group title
    Deferred Switch Group (Week 228-324) EXT 3
    Reporting group description
    		 One doravirine, tenofovir, lamivudine taken q.d. by mouth for an additional 96 weeks (Week 228 - Week 324)

    Serious adverse events
    		 Immediate Switch Group Day 1 to Week 24 Deferred Switch Group Double-blind Day 1 to Week 12 Deferred Switch Group Open-label Week 12-36 Immediate Switch Group only (Week 24-120) EXT 1 Deferred Switch Group (Week 36-132) EXT 1 Deferred Switch Group (Week 132-228) EXT 2 Immediate Switch Group (Week 120-216) EXT 2 Immediate Switch Group (Week 216-312) EXT 3 Deferred Switch Group (Week 228-324) EXT 3
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    1 / 42 (2.38%)
    6 / 43 (13.95%)
    2 / 41 (4.88%)
    1 / 33 (3.03%)
    3 / 39 (7.69%)
    2 / 17 (11.76%)
    0 / 19 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    1 / 17 (5.88%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    1 / 39 (2.56%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    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
    Uterine leiomyoma
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Spinal compression fracture
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    1 / 42 (2.38%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    1 / 17 (5.88%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stab wound
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    1 / 39 (2.56%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Ectopic pregnancy
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cystocele
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    1 / 39 (2.56%)
    1 / 17 (5.88%)
    0 / 19 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Conversion disorder
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 33 (3.03%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia haemophilus
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound sepsis
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    0 / 41 (0.00%)
    1 / 33 (3.03%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (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
         deaths causally related to treatment / all
    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
    		 Immediate Switch Group Day 1 to Week 24 Deferred Switch Group Double-blind Day 1 to Week 12 Deferred Switch Group Open-label Week 12-36 Immediate Switch Group only (Week 24-120) EXT 1 Deferred Switch Group (Week 36-132) EXT 1 Deferred Switch Group (Week 132-228) EXT 2 Immediate Switch Group (Week 120-216) EXT 2 Immediate Switch Group (Week 216-312) EXT 3 Deferred Switch Group (Week 228-324) EXT 3
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 43 (67.44%)
    25 / 43 (58.14%)
    26 / 42 (61.90%)
    31 / 43 (72.09%)
    33 / 41 (80.49%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    3 / 43 (6.98%)
    4 / 43 (9.30%)
    4 / 42 (9.52%)
    4 / 43 (9.30%)
    5 / 41 (12.20%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    4
    4
    5
    5
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    6 / 43 (13.95%)
    3 / 43 (6.98%)
    5 / 42 (11.90%)
    9 / 43 (20.93%)
    7 / 41 (17.07%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    8
    3
    5
    9
    9
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    11 / 43 (25.58%)
    7 / 43 (16.28%)
    3 / 42 (7.14%)
    8 / 43 (18.60%)
    14 / 41 (34.15%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    13
    9
    3
    8
    15
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    7 / 43 (16.28%)
    5 / 43 (11.63%)
    5 / 42 (11.90%)
    5 / 43 (11.63%)
    5 / 41 (12.20%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    7
    5
    5
    5
    5
    0
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 43 (2.33%)
    0 / 42 (0.00%)
    2 / 43 (4.65%)
    4 / 41 (9.76%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    2
    4
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 43 (13.95%)
    3 / 43 (6.98%)
    4 / 42 (9.52%)
    1 / 43 (2.33%)
    4 / 41 (9.76%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    6
    3
    4
    1
    4
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    5 / 43 (11.63%)
    1 / 43 (2.33%)
    1 / 42 (2.38%)
    1 / 43 (2.33%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    5
    1
    1
    1
    2
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Productive cough
         subjects affected / exposed
    0 / 43 (0.00%)
    2 / 43 (4.65%)
    0 / 42 (0.00%)
    3 / 43 (6.98%)
    1 / 41 (2.44%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    2
    0
    3
    1
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 43 (0.00%)
    2 / 42 (4.76%)
    3 / 43 (6.98%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    2
    3
    2
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 43 (2.33%)
    1 / 42 (2.38%)
    0 / 43 (0.00%)
    1 / 41 (2.44%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    1
    1
    0
    1
    0
    0
    0
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    5 / 43 (11.63%)
    3 / 43 (6.98%)
    3 / 42 (7.14%)
    5 / 43 (11.63%)
    5 / 41 (12.20%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    5
    3
    3
    6
    5
    0
    0
    0
    0
    Aggression
         subjects affected / exposed
    3 / 43 (6.98%)
    2 / 43 (4.65%)
    2 / 42 (4.76%)
    4 / 43 (9.30%)
    7 / 41 (17.07%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    2
    2
    4
    7
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 43 (4.65%)
    7 / 42 (16.67%)
    7 / 43 (16.28%)
    11 / 41 (26.83%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    3
    2
    7
    7
    11
    0
    0
    0
    0
    Confusional state
         subjects affected / exposed
    1 / 43 (2.33%)
    1 / 43 (2.33%)
    3 / 42 (7.14%)
    6 / 43 (13.95%)
    6 / 41 (14.63%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    1
    3
    6
    7
    0
    0
    0
    0
    Depressed mood
         subjects affected / exposed
    1 / 43 (2.33%)
    2 / 43 (4.65%)
    0 / 42 (0.00%)
    5 / 43 (11.63%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    2
    0
    6
    2
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    8 / 43 (18.60%)
    7 / 43 (16.28%)
    6 / 42 (14.29%)
    5 / 43 (11.63%)
    10 / 41 (24.39%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    9
    10
    6
    5
    13
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 43 (2.33%)
    4 / 42 (9.52%)
    5 / 43 (11.63%)
    8 / 41 (19.51%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    3
    1
    4
    7
    8
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 43 (6.98%)
    1 / 43 (2.33%)
    1 / 42 (2.38%)
    5 / 43 (11.63%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    4
    1
    1
    6
    2
    0
    0
    0
    0
    Arthralgia
         subjects affected / exposed
    7 / 43 (16.28%)
    1 / 43 (2.33%)
    2 / 42 (4.76%)
    4 / 43 (9.30%)
    3 / 41 (7.32%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    8
    1
    2
    4
    3
    0
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    2 / 43 (4.65%)
    2 / 43 (4.65%)
    2 / 42 (4.76%)
    4 / 43 (9.30%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    2
    2
    5
    5
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 43 (9.30%)
    6 / 43 (13.95%)
    2 / 42 (4.76%)
    4 / 43 (9.30%)
    7 / 41 (17.07%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    6
    6
    2
    5
    8
    0
    0
    0
    0
    Viral infection
         subjects affected / exposed
    1 / 43 (2.33%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    1 / 43 (2.33%)
    3 / 41 (7.32%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 43 (0.00%)
    1 / 43 (2.33%)
    0 / 42 (0.00%)
    4 / 43 (9.30%)
    4 / 41 (9.76%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    1
    0
    4
    4
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 43 (0.00%)
    0 / 43 (0.00%)
    1 / 42 (2.38%)
    2 / 43 (4.65%)
    3 / 41 (7.32%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    0
    0
    1
    3
    5
    0
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    3 / 43 (6.98%)
    0 / 43 (0.00%)
    0 / 42 (0.00%)
    0 / 43 (0.00%)
    2 / 41 (4.88%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    3
    0
    0
    0
    2
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    2 / 43 (4.65%)
    0 / 43 (0.00%)
    2 / 42 (4.76%)
    4 / 43 (9.30%)
    0 / 41 (0.00%)
    0 / 33 (0.00%)
    0 / 39 (0.00%)
    0 / 17 (0.00%)
    0 / 19 (0.00%)
         occurrences all number
    2
    0
    2
    5
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Oct 2016
    The primary purpose of Amendment 1 was to add study extension 1 to collect long-term efficacy and safety data and to incorporate changes to facilitate enrollment and ensure trial completion.
    13 Jul 2018
    The primary purpose of Amendment 2 was to add study extension 2 to provide continued access to MK-1439A for participants who are deriving benefit from MK-1439A until the drug is available locally in the country participating in the trial or for an additional 2 years.
    18 Mar 2021
    The primary purpose of Amendment 3 was to provide continued access to MK-1439A until the drug is available locally in countries participating in the trial or for an additional 2 years (whichever comes first).

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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