Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Reformulated Raltegravir 1200 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Each in Combination With TRUVADA™, in Treatment- Naïve HIV-1 Infected Subjects

    Summary
    EudraCT number
    		 2013-001939-47
    Trial protocol
    		 IT   ES   PT   BE   GB  
    Global end of trial date
    19 Dec 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Dec 2017
    First version publication date
    06 Dec 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    0518-292
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02131233
    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
    19 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Dec 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective was to evaluate the safety and efficacy of reformulated raltegravir (MK-0518) 1200 mg once daily in combination with TRUVADA™ versus raltegravir 400 mg twice daily in combination with TRUVADA™ in HIV-1 infected, treatment-naive participants. The primary hypothesis being tested is that reformulated raltegravir 1200 mg once-daily is non-inferior to raltegravir 400 mg twice-daily, each in combination therapy with TRUVADA™, as assessed by the proportion of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL at Week 48.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 May 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 16
    Country: Number of subjects enrolled
    Australia: 30
    Country: Number of subjects enrolled
    Belgium: 18
    Country: Number of subjects enrolled
    Canada: 21
    Country: Number of subjects enrolled
    Chile: 25
    Country: Number of subjects enrolled
    Colombia: 19
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Germany: 54
    Country: Number of subjects enrolled
    Guatemala: 35
    Country: Number of subjects enrolled
    Israel: 22
    Country: Number of subjects enrolled
    Italy: 44
    Country: Number of subjects enrolled
    Malaysia: 26
    Country: Number of subjects enrolled
    Peru: 8
    Country: Number of subjects enrolled
    Philippines: 10
    Country: Number of subjects enrolled
    Portugal: 29
    Country: Number of subjects enrolled
    Russian Federation: 40
    Country: Number of subjects enrolled
    South Africa: 57
    Country: Number of subjects enrolled
    Spain: 37
    Country: Number of subjects enrolled
    Switzerland: 16
    Country: Number of subjects enrolled
    Taiwan: 14
    Country: Number of subjects enrolled
    Thailand: 52
    Country: Number of subjects enrolled
    United Kingdom: 19
    Country: Number of subjects enrolled
    United States: 175
    Worldwide total number of subjects
    802
    EEA total number of subjects
    236
    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)
    795
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Males and females 18 years of age or older who were HIV-1 positive and naïve to antiretroviral therapy (ART) were enrolled in this trial.

    Period 1
    Period 1 title
    Overall Study
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Reformulated Raltegravir
    Arm description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Reformulated Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1200 mg (2x 600 mg tablets) orally once daily

    Investigational medicinal product name
    TRUVADA™
    Investigational medicinal product code
    Other name
    Emtricitabine /tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/300 mg tablet administered once daily with food (open-label)

    Arm title
    		 Raltegravir
    Arm description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg tablet orally twice daily

    Investigational medicinal product name
    TRUVADA™
    Investigational medicinal product code
    Other name
    Emtricitabine /tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/300 mg tablet administered once daily with food (open-label)

    Investigational medicinal product name
    Placebo to Reformulated Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two tablets orally twice daily

    Number of subjects in period 1
    		Reformulated Raltegravir Raltegravir
    Started
    533
    269
    Completed
    531
    266
    Not completed
    2
    3
         Not Treated
    2
    3
    Period 2
    Period 2 title
    Treated Participants
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Reformulated Raltegravir
    Arm description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Reformulated Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1200 mg (2x 600 mg tablets) orally once daily

    Investigational medicinal product name
    TRUVADA™
    Investigational medicinal product code
    Other name
    Emtricitabine /tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/300 mg tablet administered once daily with food (open-label)

    Arm title
    		 Raltegravir
    Arm description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg tablet orally twice daily

    Investigational medicinal product name
    TRUVADA™
    Investigational medicinal product code
    Other name
    Emtricitabine /tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    200/300 mg tablet administered once daily with food (open-label)

    Investigational medicinal product name
    Placebo to Reformulated Raltegravir
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two tablets orally twice daily

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: Period 1, enrolled participants, was not the baseline period. Instead Period 2, treated participants, was assigned as the baseline period.
    Number of subjects in period 2 [2]
    		Reformulated Raltegravir Raltegravir
    Started
    531
    266
    Completed
    467
    227
    Not completed
    64
    39
         Adverse event, serious fatal
    -
    1
         Physician decision
    7
    -
         Consent withdrawn by subject
    18
    11
         Adverse event, non-fatal
    7
    6
         Non-Compliance With Study Drug
    8
    5
         Pregnancy
    4
    -
         Lost to follow-up
    14
    13
         Lack of efficacy
    6
    3
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The worldwide number of enrolled participants, was not the baseline period. Instead treated participants, was assigned as the baseline period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Reformulated Raltegravir
    Reporting group description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks.

    Reporting group title
    Raltegravir
    Reporting group description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks.

    Reporting group values
    		 Reformulated Raltegravir Raltegravir Total
    Number of subjects
    		 531 266 797
    Age Categorical
    Treated Participants
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 527 263 790
        From 65-84 years
    		 4 3 7
        85 years and over
    		 0 0 0
    Age Continuous
    Treated Participants
    Units: years
        arithmetic mean (standard deviation)
    		 35.4 ( 10.3 ) 36.9 ( 11.0 ) -
    Gender Categorical
    Treated Participants
    Units: Subjects
        Female
    		 91 32 123
        Male
    		 440 234 674
    Subject analysis sets

    Subject analysis set title
    Reformulated Raltegravir
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks

    Subject analysis set title
    Raltegravir
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

    Subject analysis sets values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects
    531
    266
    Age Categorical
    Treated Participants
    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)
    527
    263
        From 65-84 years
    4
    3
        85 years and over
    0
    0
    Age Continuous
    Treated Participants
    Units: years
        arithmetic mean (standard deviation)
    35.4 ( 10.3 )
    36.9 ( 11.0 )
    Gender Categorical
    Treated Participants
    Units: Subjects
        Female
    91
    32
        Male
    440
    234

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Reformulated Raltegravir
    Reporting group description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks.

    Reporting group title
    Raltegravir
    Reporting group description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks.
    Reporting group title
    Reformulated Raltegravir
    Reporting group description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks.

    Reporting group title
    Raltegravir
    Reporting group description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks.

    Subject analysis set title
    Reformulated Raltegravir
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks

    Subject analysis set title
    Raltegravir
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

    Primary: Percentage of Participants Achieving <40 copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving <40 copies/mL Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Week 48
    End point description
    From blood samples collected at week 48, HIV-1 RNA levels were determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL. The NC=F approach as defined by FDA “snapshot” approach was used as the primary approach to analysis where all missing data were treated as failures regardless of the reason. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (confidence interval 95%)
    88.9 (85.9 to 91.4)
    88.3 (83.9 to 91.9)
    Statistical analysis title
    		 Reformulated Raltegravir minus Raltegravir
    Statistical analysis description
    The 95% Confidence Interval (CI) for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA <=100,000 copies/mL or HIV-1 RNA >100,000 copies/mL).
    Comparison groups
    Reformulated Raltegravir v Raltegravir
    Number of subjects included in analysis
    797
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.204
         upper limit
    		 5.223
    Notes
    [1] - Reformulated Raltegravir is concluded non-inferior to Raltegravir if the lower bound of the 95% CI for the difference in percent response is above -10 percentage points.

    Secondary: Percentage of Participants Achieving <40 copies/mL HIV RNA at Week 96

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving <40 copies/mL HIV RNA at Week 96
    End point description
    From blood samples collected at week 96, HIV-1 RNA levels were determined by the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification (LoQ) of 40 copies/mL. The NC=F approach as defined by FDA “snapshot” approach was used as the primary approach to analysis where all missing data were treated as failures regardless of the reason. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Week 96
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    81.5
    80.1
    Statistical analysis title
    		 Reformulated Raltegravir minus Raltegravir
    Statistical analysis description
    The 95% Confidence Interval (CI) for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (screening HIV-1 RNA <=100,000 copies/mL or HIV-1 RNA >100,000 copies/mL).
    Comparison groups
    Reformulated Raltegravir v Raltegravir
    Number of subjects included in analysis
    797
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Estimated Difference
    Point estimate
    1.449
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.41
         upper limit
    		 7.308
    Notes
    [2] - Reformulated Raltegravir is concluded noninferior to Raltegravir if the lower bound of the 95% CI for the difference in percent response is above -10 percentage points.

    Secondary: Change from Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48

    		 Close Top of page
    End point title
    		 Change from Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48
    End point description
    CD4 cells were counted from blood collected at baseline and week 48, and the change from baseline determined from week 48 minus baseline values.The population analyzed was all randomized participants who received at least one dose of study treatment and have baseline data. The Observed Failure (OF) approach to handling missing values assumed baseline-carry-forward for all failures, and excluded other missing values.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    499
    251
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    232.0 (214.6 to 249.4)
    234.1 (212.8 to 255.3)
    Statistical analysis title
    		 Reformulated Raltegravir minus Raltegravir
    Statistical analysis description
    The 95% CI for mean difference in CD4 change was based on t-distribution.
    Comparison groups
    Reformulated Raltegravir v Raltegravir
    Number of subjects included in analysis
    750
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean Difference (Final Values)
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -30.9
         upper limit
    		 26.7

    Secondary: Change from Baseline in CD4 Cell Count at Week 96

    		 Close Top of page
    End point title
    		 Change from Baseline in CD4 Cell Count at Week 96
    End point description
    CD4 cells were counted from blood collected at baseline and week 96, and the change from baseline determined from week 96 minus baseline values. The population analyzed was all randomized participants who received at least one dose of study treatment and have baseline data. The Observed Failure (OF) approach to handling missing values assumed baseline-carry-forward for all failures, and excluded other missing values.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 96
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    482
    235
    Units: cells/mm^3
        arithmetic mean (confidence interval 95%)
    261.6 (242.9 to 280.3)
    262.2 (236.4 to 288.0)
    Statistical analysis title
    		 Reformulated Raltegravir minus Raltegravir
    Statistical analysis description
    The 95% CI for mean difference in CD4 change was based on t-distribution.
    Comparison groups
    Reformulated Raltegravir v Raltegravir
    Number of subjects included in analysis
    717
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean Difference (Final Values)
    Point estimate
    -0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.8
         upper limit
    		 31.6

    Secondary: Percentage of Participants with an Adverse Event (AE) at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with an Adverse Event (AE) at Week 48
    End point description
    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    83.2
    88.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an AE after 96 weeks of Treatment

    		 Close Top of page
    End point title
    		 Percentage of Participants with an AE after 96 weeks of Treatment
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    90.8
    94.0
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Drug-Related AE at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with a Drug-Related AE at Week 48
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. An investigator who is a qualified physician evaluated whether or not an AE was drug-related. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    25.0
    27.1
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Drug-Related AE after 96 weeks of Treatment

    		 Close Top of page
    End point title
    		 Percentage of Participants with a Drug-Related AE after 96 weeks of Treatment
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. An investigator who is a qualified physician evaluated whether or not an AE was drug-related. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    26.4
    28.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Serious Adverse Event (SAE) at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with a Serious Adverse Event (SAE) at Week 48
    End point description
    A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    6.2
    9.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants with SAE after 96 weeks of Treatment

    		 Close Top of page
    End point title
    		 Percentage of Participants with SAE after 96 weeks of Treatment
    End point description
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    9.6
    15.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Serious and Drug-Related AE at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants with a Serious and Drug-Related AE at Week 48
    End point description
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician evaluated whether or not a SAE is drug-related.The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    0.2
    0.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants with a Serious and Drug-Related AE after 96 weeks of Treatment

    		 Close Top of page
    End point title
    		 Percentage of Participants with a Serious and Drug-Related AE after 96 weeks of Treatment
    End point description
    A SAE is any AE occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. An investigator who is a qualified physician evaluated whether or not a SAE is drug-related. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    0.2
    0.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Discontinued from Drug Therapy Due to an AE at Week 48

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Discontinued from Drug Therapy Due to an AE at Week 48
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 48
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    1.1
    2.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Discontinued from Drug Therapy Due to an AE up to Week 96

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Discontinued from Drug Therapy Due to an AE up to Week 96
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), 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. The population analyzed was all randomized participants who received at least one dose of study treatment.
    End point type
    Secondary
    End point timeframe
    Up to Week 96
    End point values
    		 Reformulated Raltegravir Raltegravir
    Number of subjects analysed
    531
    266
    Units: Percentage of participants
        number (not applicable)
    1.3
    2.3
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 98 (96 weeks of treatment + 2 weeks of follow up)
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Raltegravir 1200 mg QD + Truvada
    Reporting group description
    		 Reformulated raltegravir 1200 mg (2x 600 mg tablets) orally once daily plus placebo to raltegravir 1 tablet orally twice daily plus TRUVADA™ orally once daily for 96 weeks

    Reporting group title
    Raltegravir 400 mg BID + Truvada
    Reporting group description
    		 Raltegravir 400 mg tablet orally twice daily plus placebo to reformulated raltegravir 2 tablets orally once daily plus TRUVADA™ orally once daily for 96 weeks

    Serious adverse events
    		 Raltegravir 1200 mg QD + Truvada Raltegravir 400 mg BID + Truvada
    Total subjects affected by serious adverse events
         subjects affected / exposed
    51 / 531 (9.60%)
    42 / 266 (15.79%)
         number of deaths (all causes)
    2
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of salivary gland
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal squamous cell carcinoma
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anogenital warts
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bowen's disease
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breast cancer in situ
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Burkitt's lymphoma
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immunoblastic lymphoma
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive crisis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drug ineffective
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcoholism
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    4 / 531 (0.75%)
    2 / 266 (0.75%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emotional distress
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    2 / 531 (0.38%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Schizophrenia
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicidal ideation
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial bones fracture
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 531 (0.19%)
    2 / 266 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal perforation
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intussusception
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    2 / 531 (0.38%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteochondrosis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal wall abscess
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acquired immunodeficiency syndrome
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Anal abscess
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 531 (0.19%)
    2 / 266 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral toxoplasmosis
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis C
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphogranuloma venereum
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis tuberculous
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmodium vivax infection
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis chlamydial
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctitis infectious
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syphilis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 531 (0.19%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    1 / 531 (0.19%)
    0 / 266 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 531 (0.00%)
    1 / 266 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Raltegravir 1200 mg QD + Truvada Raltegravir 400 mg BID + Truvada
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    375 / 531 (70.62%)
    184 / 266 (69.17%)
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    26 / 531 (4.90%)
    18 / 266 (6.77%)
         occurrences all number
    31
    19
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    29 / 531 (5.46%)
    17 / 266 (6.39%)
         occurrences all number
    35
    25
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    39 / 531 (7.34%)
    19 / 266 (7.14%)
         occurrences all number
    46
    20
    Headache
         subjects affected / exposed
    84 / 531 (15.82%)
    37 / 266 (13.91%)
         occurrences all number
    106
    45
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    40 / 531 (7.53%)
    17 / 266 (6.39%)
         occurrences all number
    44
    19
    Influenza like illness
         subjects affected / exposed
    14 / 531 (2.64%)
    14 / 266 (5.26%)
         occurrences all number
    16
    19
    Pyrexia
         subjects affected / exposed
    26 / 531 (4.90%)
    15 / 266 (5.64%)
         occurrences all number
    30
    16
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    46 / 531 (8.66%)
    12 / 266 (4.51%)
         occurrences all number
    57
    15
    Diarrhoea
         subjects affected / exposed
    71 / 531 (13.37%)
    34 / 266 (12.78%)
         occurrences all number
    82
    42
    Nausea
         subjects affected / exposed
    72 / 531 (13.56%)
    34 / 266 (12.78%)
         occurrences all number
    88
    38
    Vomiting
         subjects affected / exposed
    42 / 531 (7.91%)
    20 / 266 (7.52%)
         occurrences all number
    45
    24
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    40 / 531 (7.53%)
    17 / 266 (6.39%)
         occurrences all number
    48
    19
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    18 / 531 (3.39%)
    17 / 266 (6.39%)
         occurrences all number
    21
    18
    Rash
         subjects affected / exposed
    30 / 531 (5.65%)
    13 / 266 (4.89%)
         occurrences all number
    35
    14
    Psychiatric disorders
    Depression
         subjects affected / exposed
    17 / 531 (3.20%)
    15 / 266 (5.64%)
         occurrences all number
    19
    17
    Insomnia
         subjects affected / exposed
    31 / 531 (5.84%)
    18 / 266 (6.77%)
         occurrences all number
    31
    18
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    27 / 531 (5.08%)
    7 / 266 (2.63%)
         occurrences all number
    32
    9
    Back pain
         subjects affected / exposed
    39 / 531 (7.34%)
    14 / 266 (5.26%)
         occurrences all number
    47
    15
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    29 / 531 (5.46%)
    14 / 266 (5.26%)
         occurrences all number
    32
    16
    Influenza
         subjects affected / exposed
    31 / 531 (5.84%)
    18 / 266 (6.77%)
         occurrences all number
    41
    22
    Nasopharyngitis
         subjects affected / exposed
    65 / 531 (12.24%)
    26 / 266 (9.77%)
         occurrences all number
    88
    35
    Syphilis
         subjects affected / exposed
    28 / 531 (5.27%)
    19 / 266 (7.14%)
         occurrences all number
    30
    21
    Upper respiratory tract infection
         subjects affected / exposed
    67 / 531 (12.62%)
    27 / 266 (10.15%)
         occurrences all number
    90
    37

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Oct 2014
    Amendment 1 was to extend the screening period time as well as to modify the inclusion criteria regarding birth control to allow local regulations to be followed. In addition there was additional text added to define antiretroviral therapy to be used during the trial; define complete physical examination; define type of meal consumed before or after dose of study medication; update to emergency call center information; update regarding unblended trial statistician; additional details for local discard requirements.
    08 Sep 2015
    Amendment 2 was completed to switch from electronic to paper study diaries.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed Apr 24 07:21:35 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA