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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38529   clinical trials with a EudraCT protocol, of which   6333   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).
     
    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:
    Multicenter, Double-Blind, Randomized, 2-Part, Dose Ranging Study to Compare the Safety, and Antiretroviral Activity of MK-1439 Plus TRUVADA Versus Efavirenz Plus TRUVADA in Antiretroviral Treatment-Naive, HIV-1 Infected Patients

    Summary
    EudraCT number
    2012-001573-93
    Trial protocol
    DE   ES   BE   NL   PL  
    Global end of trial date
    21 Mar 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    01 Apr 2017
    First version publication date
    01 Apr 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    1439-007
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01632345
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., 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
    31 Dec 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Dec 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part 1 - Dose-Ranging. Evaluated the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of doravirine (MK-1439) compared with efavirenz, each given in combination with TRUVADA® (emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg) for at least 24 weeks. A single dose of doravirine was selected for further study after all participants completed the Week 24 visit. Part 2 - Selected Dose. Evaluated the safety of the selected dose of doravirine compared with efavirenz through Week 96, particularly with regard to early onset (by Week 8 and 24) of central nervous system adverse events (CNS events). The hypothesis tested in this study was that MK-1439 at the final dose selected is superior to efavirenz, each given in combination with TRUVADA, as measured by the proportion of participants with CNS events by Week 8. If superiority was established at Week 8, the same hypothesis was tested for Week 24.
    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
    15 Oct 2012
    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
    Spain: 45
    Country: Number of subjects enrolled
    United States: 100
    Country: Number of subjects enrolled
    Australia: 31
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Canada: 14
    Country: Number of subjects enrolled
    France: 17
    Country: Number of subjects enrolled
    Germany: 56
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Puerto Rico: 27
    Country: Number of subjects enrolled
    Romania: 26
    Country: Number of subjects enrolled
    Russian Federation: 16
    Worldwide total number of subjects
    340
    EEA total number of subjects
    152
    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)
    336
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    The study enrolled 342 treatment-naïve HIV-infected participants, 18 years of age or older with baseline HIV RNA of at least 1,000 copies/mL and baseline CD4 cell counts of at least 100 cells/mm3. Two of the enrolled participants never received treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Doravirine 25 mg: Part I
    Arm description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Doravirine
    Investigational medicinal product code
    MK-1439
    Other name
    Pharmaceutical forms
    Tablet, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Doravirine 50 mg: Part I
    Arm description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Doravirine
    Investigational medicinal product code
    MK-1439
    Other name
    Pharmaceutical forms
    Tablet, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Doravirine 100 mg: Part I
    Arm description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Doravirine
    Investigational medicinal product code
    MK-1439
    Other name
    Pharmaceutical forms
    Tablet, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Doravirine 200 mg: Part I
    Arm description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Doravirine
    Investigational medicinal product code
    MK-1439
    Other name
    Pharmaceutical forms
    Tablet, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Efavirenz 600 mg: Part I
    Arm description
    Efavirenz 600 mg once daily plus TRUVADA once daily
    Arm type
    Active comparator

    Investigational medicinal product name
    Efavirenz
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Doravirine 100 mg: Part II
    Arm description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily
    Arm type
    Experimental

    Investigational medicinal product name
    Doravirine
    Investigational medicinal product code
    MK-1439
    Other name
    Pharmaceutical forms
    Tablet, Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg administered once daily plus TRUVADA administered once daily

    Arm title
    Efavirenz 600 mg: Part II
    Arm description
    Efavirenz 600 mg once daily plus TRUVADA once daily
    Arm type
    Active comparator

    Investigational medicinal product name
    Efavirenz
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg administered once daily plus TRUVADA administered once daily

    Number of subjects in period 1
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I Doravirine 100 mg: Part II Efavirenz 600 mg: Part II
    Started
    40
    43
    42
    41
    42
    66
    66
    Completed
    28
    28
    32
    33
    29
    55
    55
    Not completed
    12
    15
    10
    8
    13
    11
    11
         Protocol deviation
    -
    -
    1
    1
    -
    -
    -
         Physician decision
    2
    1
    -
    -
    1
    -
    -
         Non-compliance with study drug
    3
    2
    2
    1
    -
    3
    -
         Lack of efficacy
    -
    1
    -
    1
    1
    -
    -
         Pregnancy
    -
    1
    -
    -
    -
    -
    -
         Participant withdrawal
    3
    4
    4
    1
    4
    2
    2
         Adverse event, non-fatal
    1
    4
    2
    1
    3
    3
    8
         Lost to follow-up
    3
    2
    1
    3
    4
    3
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    Randomised/Treated Participants

    Reporting group values
    Overall Study Total
    Number of subjects
    340 340
    Age Categorical
    Two randomised participants who were enrolled in the overall population (n=342) never received treatment.
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    336 336
        From 65-84 years
    4 4
        85 years and over
    0 0
    Age Continuous
    Two enrolled participants in the overall population who were randomized (n=342) never received treatment.
    Units: years
        arithmetic mean (full range (min-max))
    36.4 (19 to 69) -
    Gender Categorical
    Units: Subjects
        Female
    315 315
        Male
    25 25
    Subject analysis sets

    Subject analysis set title
    Doravirine 25 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 50 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 100 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 200 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Efavirenz 600 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 25 mg: PartI/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 50 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 100 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 200 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Efavirenz 600 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Subject analysis sets values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I Doravirine 25 mg: PartI/II Combined Doravirine 50 mg: Part I/II Combined Doravirine 100 mg: Part I/II Combined Doravirine 200 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects
    40
    43
    42
    41
    42
    40
    43
    108
    41
    108
    Age Categorical
    Two randomised participants who were enrolled in the overall population (n=342) never received treatment.
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Adults (18-64 years)
    38
    42
    41
    41
    42
    38
    42
    107
    41
    108
        From 65-84 years
    2
    1
    1
    0
    0
    2
    1
    1
    0
    0
        85 years and over
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Age Continuous
    Two enrolled participants in the overall population who were randomized (n=342) never received treatment.
    Units: years
        arithmetic mean (full range (min-max))
    38.9 (21 to 69)
    38.3 (25 to 66)
    36.5 (19 to 67)
    34.4 (23 to 50)
    35 (22 to 54)
    38.9 (21 to 69)
    38.3 (25 to 66)
    36.8 (19 to 67)
    34.4 (21 to 50)
    35.2 (20 to 57)
    Gender Categorical
    Units: Subjects
        Female
    38
    37
    36
    40
    38
    38
    37
    99
    40
    101
        Male
    2
    6
    6
    1
    4
    2
    6
    9
    1
    7

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Doravirine 25 mg: Part I
    Reporting group description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 50 mg: Part I
    Reporting group description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 100 mg: Part I
    Reporting group description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 200 mg: Part I
    Reporting group description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Reporting group title
    Efavirenz 600 mg: Part I
    Reporting group description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 100 mg: Part II
    Reporting group description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Reporting group title
    Efavirenz 600 mg: Part II
    Reporting group description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 25 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 50 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 100 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 200 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Efavirenz 600 mg: Part I
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 25 mg: PartI/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 50 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 100 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Doravirine 200 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Subject analysis set title
    Efavirenz 600 mg: Part I/II Combined
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Primary: Percentage of Participants With At Least 1 Adverse Event (AE) in Weeks 0-24: MK-1439 All Doses vs. Efavirenz (Part I)

    Close Top of page
    End point title
    Percentage of Participants With At Least 1 Adverse Event (AE) in Weeks 0-24: MK-1439 All Doses vs. Efavirenz (Part I)
    End point description
    A primary endpoint in Part I was the percentage of participants receiving doravirine (MK-1439) at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. The relative number (n/N [%]) of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-24.
    End point type
    Primary
    End point timeframe
    Up to Week 24
    End point values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I
    Number of subjects analysed
    40
    43
    42
    41
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    90 (76.3 to 97.2)
    93 (80.9 to 98.5)
    71.4 (55.4 to 84.3)
    85.4 (70.8 to 94.4)
    83.3 (68.6 to 93)
    Statistical analysis title
    Relative % of participants with ≥1 AE
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 25 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    6.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9
         upper limit
    22.4
    Statistical analysis title
    Relative % of participants with ≥1 AE
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 50 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    9.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.6
         upper limit
    24.9
    Statistical analysis title
    Relative % of participants with ≥1 AE
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -11.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -29.7
         upper limit
    6.3
    Statistical analysis title
    Relative % of participants with ≥1 AE
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 200 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.5
         upper limit
    18.4

    Primary: Percentage of Participants with At Least 1 AE in Weeks 0-24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with At Least 1 AE in Weeks 0-24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A primary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with ≥1 AE was primarily assessed for Weeks 0-24.
    End point type
    Primary
    End point timeframe
    Up to Week 24
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    108
    Units: percentage of participants
        number (confidence interval 95%)
    75 (65.7 to 82.8)
    85.2 (77.1 to 91.3)
    Statistical analysis title
    Relative % of participants with ≥1 AE
    Statistical analysis description
    Doravirine minus Eftavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    216
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -10.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -20.9
         upper limit
    0.5

    Primary: Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: MK-1439 All Doses vs. Efavirenz (Part I)

    Close Top of page
    End point title
    Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: MK-1439 All Doses vs. Efavirenz (Part I)
    End point description
    A primary endpoint in Part I was the percentage of participants receiving doravirine (MK-1439) at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who discontinued study therapy due to AEs. The relative number (n/N [%]) of participants who discontinued due to AEs was primarily assessed for Weeks 0-24.
    End point type
    Primary
    End point timeframe
    Up to Week 24
    End point values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I
    Number of subjects analysed
    40
    43
    42
    41
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    2.5 (0.1 to 13.2)
    7 (1.5 to 19.1)
    2.4 (0.1 to 12.6)
    0 (0 to 8.6)
    4.8 (0.6 to 16.2)
    Statistical analysis title
    Relative % of participants discontinued for AEs
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 25 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.7
         upper limit
    8.8
    Statistical analysis title
    Relative % of participants discontinued for AEs
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 50 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    2.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.9
         upper limit
    14.7
    Statistical analysis title
    Relative % of participants discontinued for AEs
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -2.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.8
         upper limit
    8.2
    Statistical analysis title
    Relative % of participants discontinued for AEs
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 200 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -4.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.9
         upper limit
    4.1

    Primary: Percentage of Participants with Central Nervous System (CNS) Events by Week 8: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Central Nervous System (CNS) Events by Week 8: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A key primary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had CNS Events over 8 weeks of treatment. Although 24 individual CNS events were described, they were pooled and evaluated as CNS events. The relative number (n/N [%]) of participants in either treatment group with CNS events was primarily assessed for Week 8.
    End point type
    Primary
    End point timeframe
    Up to Week 8
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    108
    Units: Percentage of participants
        number (confidence interval 95%)
    24.1 (16.4 to 33.3)
    44.4 (34.9 to 54.3)
    Statistical analysis title
    Relative % of participants with CNS events
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    216
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Miettinen and Nurminen method
    Parameter type
    Between-treatment difference
    Point estimate
    -20.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -32.4
         upper limit
    -7.8

    Primary: Percentage of Participants with CNS Events by Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with CNS Events by Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A key primary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had CNS events over 24 weeks of treatment. Although 24 individual CNS AEs were described, they were pooled and evaluated as CNS events. The relative number (n/N [%]) of participants in either treatment group with CNS AEs was primarily assessed for Week 24.
    End point type
    Primary
    End point timeframe
    Up to Week 24
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    108
    Units: Percentage of participants
        number (confidence interval 95%)
    26.9 (18.8 to 36.2)
    47.2 (37.5 to 57.1)
    Statistical analysis title
    Relative % of participants with CNS events
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    216
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Miettinen and Nurminen method
    Parameter type
    Between-treatment difference
    Point estimate
    -20.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -32.6
         upper limit
    -7.5

    Primary: Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)
    End point description
    A primary endpoint in Part I was the percentage of participants receiving doravirine (MK-1439) at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 40 copies/mL) over 24 weeks of treatment. The relative number (n/N [%]) of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy.
    End point type
    Primary
    End point timeframe
    Week 24
    End point values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I
    Number of subjects analysed
    40
    43
    42
    41
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    80 (64.4 to 90.9)
    74.4 (58.8 to 86.5)
    71.4 (55.4 to 84.3)
    80.5 (65.1 to 91.2)
    64.3 (48 to 78.4)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 25 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    15.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.1
         upper limit
    34.4
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 50 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    10
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.6
         upper limit
    29.1
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    6.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.2
         upper limit
    26
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 200 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    15.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.4
         upper limit
    34.4

    Primary: Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A primary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 40 copies/mL) over 24 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy.
    End point type
    Primary
    End point timeframe
    Week 24
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    78
    79
    Units: Percentage of participants
        number (confidence interval 95%)
    72.9 (63.4 to 81)
    73.1 (63.8 to 81.2)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    157
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.3
         upper limit
    11.2

    Secondary: Percentage of Participants with At Least 1 AE in Weeks 0-48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with At Least 1 AE in Weeks 0-48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 48 weeks of treatment. The relative number (n/N [%]) of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-48.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    108
    Units: Percentage of participants
        number (confidence interval 95%)
    87 (79.2 to 92.7)
    89.8 (82.5 to 94.8)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with At Least 1 AE in Weeks 0-96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with At Least 1 AE in Weeks 0-96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE was primarily assessed for Weeks 0-96, plus a 14-day post-treatment follow-up period.
    End point type
    Secondary
    End point timeframe
    Up to 98 weeks
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    108
    Units: Percentage of participants
        number (confidence interval 95%)
    89.8 (82.5 to 94.8)
    96.3 (90.8 to 99)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)
    End point description
    A secondary endpoint in Part I was the percentage of participants receiving doravirine (MK-1439) at all doses (25 mg, 50 mg, 100 mg, and 200 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 200 copies/mL) over 24 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy.
    End point type
    Secondary
    End point timeframe
    Up to Week 24
    End point values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I
    Number of subjects analysed
    40
    43
    42
    41
    42
    Units: Percentage of participants
        number (confidence interval 95%)
    85 (70.2 to 94.3)
    83.7 (69.3 to 93.2)
    92.9 (80.5 to 98.5)
    90.2 (76.9 to 97.3)
    81 (65.9 to 91.4)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 25 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    4.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.5
         upper limit
    21.5
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 50 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    2.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -13.9
         upper limit
    19.8
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    12.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    28
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 200 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    9.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.2
         upper limit
    25.7

    Secondary: Change from Baseline in Cluster of Differentiation 4 (CD4) T Lymphocyte Cell Count at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)

    Close Top of page
    End point title
    Change from Baseline in Cluster of Differentiation 4 (CD4) T Lymphocyte Cell Count at Week 24: MK-1439 All Doses vs. Efavirenz (Part I)
    End point description
    A secondary endpoint in Part I was the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine (MK-1439) at all doses (25 mg, 50 mg, 100 mg, and 200 mg), compared with participants receiving efavirenz 600 mg. The Observed Failure (OF) approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Doravirine 25 mg: Part I Doravirine 50 mg: Part I Doravirine 100 mg: Part I Doravirine 200 mg: Part I Efavirenz 600 mg: Part I
    Number of subjects analysed
    38
    41
    41
    40
    40
    Units: cells/mm˄3
        arithmetic mean (confidence interval 95%)
    154.1 (115.1 to 193.1)
    112.9 (74.5 to 151.2)
    133.6 (100.4 to 166.8)
    140.7 (95.6 to 185.7)
    121.1 (73.3 to 169)
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 25 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    33
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -28.1
         upper limit
    94
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Comparison groups
    Doravirine 50 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -8.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -68.5
         upper limit
    51.9
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Statistical analysis description
    Doravirine minus Eftavirenz
    Comparison groups
    Doravirine 100 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    81
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    12.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -44.6
         upper limit
    69.5
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Comparison groups
    Doravirine 200 mg: Part I v Efavirenz 600 mg: Part I
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    19.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -45.1
         upper limit
    84.2

    Secondary: Change from Baseline in CD4 Cell Count at Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Change from Baseline in CD4 Cell Count at Week 24: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary objective in Part I/II combined was to assess the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned therapy due to lack of efficacy.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    106
    101
    Units: cells/mm˄3
        arithmetic mean (confidence interval 95%)
    152.3 (121.7 to 182.8)
    146 (113.1 to 178.8)
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    207
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    6.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -38.2
         upper limit
    50.8

    Secondary: Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 48: MK-1439 Selected Dose vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 48: MK-1439 Selected Dose vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 40 copies/mL) over 48 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was primarily assessed for Weeks 0-48, using the NC=F approach to handle missing data in this analysis of efficacy.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    107
    Units: Percentage of participants
        number (confidence interval 95%)
    77.8 (68.8 to 85.2)
    78.7 (69.8 to 86)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.2
         upper limit
    10

    Secondary: Change from Baseline in CD4 Cell Count at Week 48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Change from Baseline in CD4 Cell Count at Week 48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the change from baseline in the CD4 count at Week 48 in participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned therapy due to lack of efficacy.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    102
    100
    Units: cells/mm˄3
        arithmetic mean (confidence interval 95%)
    191.9 (160.8 to 223.1)
    194.5 (163.2 to 225.9)
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    202
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -2.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -46.5
         upper limit
    41.3

    Secondary: Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 40 copies/mL) at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 40 copies/mL) over 96 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was primarily assessed for Weeks 0-96, using the NC=F approach to handle missing data in this analysis of efficacy.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    81
    82
    Units: Percentage of participants
        number (confidence interval 95%)
    75 (65.7 to 82.8)
    75.9 (66.7 to 83.6)
    Statistical analysis title
    Relative % with Virologic Response
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.4
         upper limit
    10.7

    Secondary: Change from Baseline in CD4 Cell Count at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Change from Baseline in CD4 Cell Count at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the change from baseline in the CD4 count at Week 96 in participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned therapy due to lack of efficacy.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 96
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    95
    93
    Units: cells/mm˄3
        arithmetic mean (confidence interval 95%)
    259.2 (220 to 298.3)
    263.6 (218.1 to 309.1)
    Statistical analysis title
    Difference in CD4 Changes from Baseline
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    -4.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -64
         upper limit
    55.1

    Secondary: Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 48: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 200 copies/mL) over 48 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was primarily assessed for Weeks 0-48, using the NC=F approach to handle missing data in this analysis of efficacy.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    107
    Units: Percentage of participants
        number (confidence interval 95%)
    85.2 (77.1 to 91.3)
    85 (76.9 to 91.2)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.7
         upper limit
    9.9

    Secondary: Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)

    Close Top of page
    End point title
    Percentage of Participants with Virologic Response (plasma HIV RNA < 200 copies/mL) at Week 96: MK-1439 Selected Dose (100 mg) vs. Efavirenz (Part I & Part II Combined)
    End point description
    A secondary endpoint in Part I/II combined was the percentage of participants receiving doravirine (MK-1439) at the selected dose (100 mg), compared with participants receiving efavirenz 600 mg, who had a virologic response (plasma HIV RNA < 200 copies/mL) over 96 weeks of treatment. The relative number (n/N [%]) of participants in either treatment group with this virologic response was primarily assessed for Weeks 0-96, using the NC=F approach to handle missing data in this analysis of efficacy.
    End point type
    Secondary
    End point timeframe
    Up to Week 96
    End point values
    Doravirine 100 mg: Part I/II Combined Efavirenz 600 mg: Part I/II Combined
    Number of subjects analysed
    108
    107
    Units: Percentage of participants
        number (confidence interval 95%)
    79.6 (70.8 to 86.8)
    75.9 (66.7 to 83.6)
    Statistical analysis title
    Relative % with Virologic Response
    Statistical analysis description
    Doravirine minus Efavirenz
    Comparison groups
    Doravirine 100 mg: Part I/II Combined v Efavirenz 600 mg: Part I/II Combined
    Number of subjects included in analysis
    215
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    Between-treatment difference
    Point estimate
    3.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.3
         upper limit
    15

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 98 weeks
    Adverse event reporting additional description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR’s product, whether or not considered related to the use of the product.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Doravirine 25 mg (n=40)
    Reporting group description
    Doravirine (MK-1439) 25 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 50 mg (n=43)
    Reporting group description
    Doravirine (MK-1439) 50 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 100 mg (n=108)
    Reporting group description
    Doravirine (MK-1439) 100 mg once daily plus TRUVADA once daily

    Reporting group title
    Doravirine 200 mg (n=41)
    Reporting group description
    Doravirine (MK-1439) 200 mg once daily plus TRUVADA once daily

    Reporting group title
    Efavirenz 600 mg (n=108)
    Reporting group description
    Efavirenz 600 mg once daily plus TRUVADA once daily

    Serious adverse events
    Doravirine 25 mg (n=40) Doravirine 50 mg (n=43) Doravirine 100 mg (n=108) Doravirine 200 mg (n=41) Efavirenz 600 mg (n=108)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 43 (2.33%)
    11 / 108 (10.19%)
    3 / 41 (7.32%)
    13 / 108 (12.04%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Foreign body
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Jaw fracture
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Tendon rupture
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell unclassifiable lymphoma high grade
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Hodgkin's disease
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Kaposi's sarcoma
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Cardiomyopathy
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Pericardial effusion
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Hemiparesis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Peroneal nerve palsy
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Psychiatric disorders
    Bipolar I disorder
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Depression
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Drug abuse
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Suicidal ideation
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    2 / 108 (1.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary dyskinesia
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholecystitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Cholecystitis acute
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatitis toxic
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Costochondritis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Acute hepatitis C
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Cellulitis
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Cryptosporidiosis infection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Diverticulitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Gastroenteritis shigella
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatitis C
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 43 (2.33%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    1 / 41 (2.44%)
    0 / 108 (0.00%)
         occurrences causally related to treatment / all
    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
    Sinusitis
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Doravirine 25 mg (n=40) Doravirine 50 mg (n=43) Doravirine 100 mg (n=108) Doravirine 200 mg (n=41) Efavirenz 600 mg (n=108)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 40 (77.50%)
    35 / 43 (81.40%)
    78 / 108 (72.22%)
    36 / 41 (87.80%)
    82 / 108 (75.93%)
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 43 (2.33%)
    4 / 108 (3.70%)
    3 / 41 (7.32%)
    5 / 108 (4.63%)
         occurrences all number
    4
    3
    5
    10
    6
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 43 (2.33%)
    4 / 108 (3.70%)
    2 / 41 (4.88%)
    6 / 108 (5.56%)
         occurrences all number
    0
    1
    5
    2
    6
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    3 / 41 (7.32%)
    2 / 108 (1.85%)
         occurrences all number
    5
    0
    0
    3
    2
    Cough
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 43 (2.33%)
    3 / 108 (2.78%)
    3 / 41 (7.32%)
    6 / 108 (5.56%)
         occurrences all number
    7
    1
    4
    3
    10
    Dyspnoea
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 43 (6.98%)
    3 / 108 (2.78%)
    0 / 41 (0.00%)
    3 / 108 (2.78%)
         occurrences all number
    1
    3
    3
    0
    3
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 40 (12.50%)
    5 / 43 (11.63%)
    16 / 108 (14.81%)
    3 / 41 (7.32%)
    31 / 108 (28.70%)
         occurrences all number
    5
    6
    17
    3
    38
    Headache
         subjects affected / exposed
    5 / 40 (12.50%)
    6 / 43 (13.95%)
    13 / 108 (12.04%)
    7 / 41 (17.07%)
    15 / 108 (13.89%)
         occurrences all number
    6
    8
    27
    7
    26
    Somnolence
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    1 / 108 (0.93%)
         occurrences all number
    3
    0
    1
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    7 / 40 (17.50%)
    5 / 43 (11.63%)
    6 / 108 (5.56%)
    5 / 41 (12.20%)
    7 / 108 (6.48%)
         occurrences all number
    7
    7
    9
    7
    7
    Pyrexia
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 43 (2.33%)
    6 / 108 (5.56%)
    0 / 41 (0.00%)
    3 / 108 (2.78%)
         occurrences all number
    1
    1
    7
    0
    4
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 43 (0.00%)
    0 / 108 (0.00%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Psychiatric disorders
    Abnormal dreams
         subjects affected / exposed
    5 / 40 (12.50%)
    9 / 43 (20.93%)
    7 / 108 (6.48%)
    4 / 41 (9.76%)
    19 / 108 (17.59%)
         occurrences all number
    6
    9
    9
    4
    21
    Anxiety
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 43 (4.65%)
    3 / 108 (2.78%)
    0 / 41 (0.00%)
    6 / 108 (5.56%)
         occurrences all number
    1
    2
    4
    0
    9
    Depression
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 43 (6.98%)
    4 / 108 (3.70%)
    0 / 41 (0.00%)
    10 / 108 (9.26%)
         occurrences all number
    1
    4
    4
    0
    12
    Insomnia
         subjects affected / exposed
    1 / 40 (2.50%)
    6 / 43 (13.95%)
    10 / 108 (9.26%)
    3 / 41 (7.32%)
    6 / 108 (5.56%)
         occurrences all number
    1
    6
    10
    4
    7
    Nightmare
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 43 (2.33%)
    9 / 108 (8.33%)
    0 / 41 (0.00%)
    10 / 108 (9.26%)
         occurrences all number
    1
    1
    10
    0
    12
    Sleep disorder
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 43 (4.65%)
    6 / 108 (5.56%)
    0 / 41 (0.00%)
    8 / 108 (7.41%)
         occurrences all number
    1
    2
    6
    0
    11
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 40 (7.50%)
    3 / 43 (6.98%)
    5 / 108 (4.63%)
    0 / 41 (0.00%)
    4 / 108 (3.70%)
         occurrences all number
    3
    3
    5
    0
    4
    Abdominal pain upper
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 43 (6.98%)
    4 / 108 (3.70%)
    2 / 41 (4.88%)
    5 / 108 (4.63%)
         occurrences all number
    2
    3
    5
    2
    9
    Constipation
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 43 (9.30%)
    2 / 108 (1.85%)
    0 / 41 (0.00%)
    4 / 108 (3.70%)
         occurrences all number
    2
    4
    2
    0
    4
    Diarrhoea
         subjects affected / exposed
    10 / 40 (25.00%)
    4 / 43 (9.30%)
    16 / 108 (14.81%)
    5 / 41 (12.20%)
    18 / 108 (16.67%)
         occurrences all number
    10
    4
    18
    5
    20
    Haemorrhoids
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 43 (2.33%)
    4 / 108 (3.70%)
    0 / 41 (0.00%)
    6 / 108 (5.56%)
         occurrences all number
    1
    1
    4
    0
    6
    Nausea
         subjects affected / exposed
    3 / 40 (7.50%)
    7 / 43 (16.28%)
    13 / 108 (12.04%)
    9 / 41 (21.95%)
    11 / 108 (10.19%)
         occurrences all number
    3
    8
    16
    9
    12
    Vomiting
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 43 (2.33%)
    6 / 108 (5.56%)
    1 / 41 (2.44%)
    7 / 108 (6.48%)
         occurrences all number
    4
    1
    7
    1
    8
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 43 (6.98%)
    2 / 108 (1.85%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences all number
    2
    3
    2
    0
    0
    Night sweats
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    6 / 108 (5.56%)
         occurrences all number
    1
    0
    2
    0
    6
    Pruritus
         subjects affected / exposed
    0 / 40 (0.00%)
    3 / 43 (6.98%)
    4 / 108 (3.70%)
    0 / 41 (0.00%)
    3 / 108 (2.78%)
         occurrences all number
    0
    3
    4
    0
    3
    Rash
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 43 (6.98%)
    6 / 108 (5.56%)
    2 / 41 (4.88%)
    9 / 108 (8.33%)
         occurrences all number
    1
    6
    6
    2
    10
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 43 (4.65%)
    6 / 108 (5.56%)
    3 / 41 (7.32%)
    3 / 108 (2.78%)
         occurrences all number
    2
    2
    6
    3
    3
    Back pain
         subjects affected / exposed
    2 / 40 (5.00%)
    5 / 43 (11.63%)
    6 / 108 (5.56%)
    2 / 41 (4.88%)
    10 / 108 (9.26%)
         occurrences all number
    2
    7
    7
    2
    14
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 43 (6.98%)
    2 / 108 (1.85%)
    2 / 41 (4.88%)
    1 / 108 (0.93%)
         occurrences all number
    1
    3
    2
    2
    2
    Bronchitis
         subjects affected / exposed
    5 / 40 (12.50%)
    3 / 43 (6.98%)
    5 / 108 (4.63%)
    5 / 41 (12.20%)
    12 / 108 (11.11%)
         occurrences all number
    7
    5
    5
    7
    13
    Conjunctivitis
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 43 (4.65%)
    6 / 108 (5.56%)
    0 / 41 (0.00%)
    3 / 108 (2.78%)
         occurrences all number
    1
    2
    7
    0
    3
    Gastroenteritis
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 43 (4.65%)
    9 / 108 (8.33%)
    2 / 41 (4.88%)
    1 / 108 (0.93%)
         occurrences all number
    2
    3
    10
    2
    1
    Influenza
         subjects affected / exposed
    6 / 40 (15.00%)
    2 / 43 (4.65%)
    3 / 108 (2.78%)
    5 / 41 (12.20%)
    2 / 108 (1.85%)
         occurrences all number
    9
    2
    3
    5
    2
    Nasopharyngitis
         subjects affected / exposed
    3 / 40 (7.50%)
    5 / 43 (11.63%)
    19 / 108 (17.59%)
    12 / 41 (29.27%)
    13 / 108 (12.04%)
         occurrences all number
    4
    12
    31
    17
    16
    Oral herpes
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 43 (2.33%)
    2 / 108 (1.85%)
    3 / 41 (7.32%)
    3 / 108 (2.78%)
         occurrences all number
    0
    1
    3
    3
    3
    Pharyngitis
         subjects affected / exposed
    0 / 40 (0.00%)
    5 / 43 (11.63%)
    5 / 108 (4.63%)
    2 / 41 (4.88%)
    3 / 108 (2.78%)
         occurrences all number
    0
    5
    7
    2
    4
    Sinusitis
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 43 (4.65%)
    5 / 108 (4.63%)
    3 / 41 (7.32%)
    5 / 108 (4.63%)
         occurrences all number
    2
    2
    7
    4
    7
    Syphilis
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 43 (2.33%)
    6 / 108 (5.56%)
    6 / 41 (14.63%)
    8 / 108 (7.41%)
         occurrences all number
    6
    2
    7
    7
    9
    Tinea pedis
         subjects affected / exposed
    3 / 40 (7.50%)
    0 / 43 (0.00%)
    1 / 108 (0.93%)
    0 / 41 (0.00%)
    0 / 108 (0.00%)
         occurrences all number
    3
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 43 (2.33%)
    1 / 108 (0.93%)
    3 / 41 (7.32%)
    4 / 108 (3.70%)
         occurrences all number
    2
    1
    1
    3
    4
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 40 (10.00%)
    2 / 43 (4.65%)
    10 / 108 (9.26%)
    3 / 41 (7.32%)
    13 / 108 (12.04%)
         occurrences all number
    5
    6
    14
    3
    19

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Jun 2012
    The study flow chart, inclusion criteria, and treatment follow-up were clarified, and the IND number was added to the Title page.
    17 Oct 2012
    Prohibited medications and clarifications from protocol clarification letters were added. The statistical analysis sections was clarified, minor grammatical changes were made, and the inclusion and exclusion criteria were renumbered and expanded.

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA