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    Clinical Trial Results:
    A Study to Compare the Pharmacokinetics of a Fixed-Dose Combination of Raltegravir and Lamivudine to Co-administered Raltegravir and Lamivudine

    Summary
    EudraCT number
    		 2015-002237-22
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    25 Sep 2011

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Mar 2016
    First version publication date
    15 Jul 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MK-0518B-196
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    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)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001442-PIP01-13
    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
    25 Sep 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Sep 2011
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Sep 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Assess the plasma pharmacokinetic profiles of raltegravir and lamivudine after administration of MK-0518B (Formulation #6) and coadministration of the marketed Isentress 400 mg and Epivir 150 mg tablets.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Sep 2011
    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
    Canada: 24
    Worldwide total number of subjects
    24
    EEA total number of subjects
    0
    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)
    24
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study population included non-smoking, male and female volunteers from 18 to 55 years of age, with a BMI ≤ 31kg/m2,who were judged to be healthy based on a medical history, ECG, laboratory evaluation and physical examination and vital signs measurements. Twenty-four (24) male and female participants met all selection criteria.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Isentress™ + Epivir™ then MK-0518B
    Arm description
    		 Participants received single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 1 then a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    raltegravir
    Investigational medicinal product code
    Other name
    Isentress™
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Isentress™ (raltegravir) 400 mg tablets were administered with 240 mL water after a fast of at least 10 hours.

    Investigational medicinal product name
    lamivudine
    Investigational medicinal product code
    Other name
    Epivir™
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Epivir™ (lamivudine) 150 mg tablets were administered with 240 mL water after a fast of at least 10 hours

    Investigational medicinal product name
    MK-0518B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MK-0518B 300 mg reformulated raltegravir / 150 mg lamivudine monolithic tablets were administered with 240 mL water after a fast of at least 10 hours.

    Arm title
    		 Sequence 2: MK-0518B then Isentress™ + Epivir™
    Arm description
    		 Participants received a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 1 then single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    raltegravir
    Investigational medicinal product code
    Other name
    Isentress™
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Isentress™ (raltegravir) 400 mg tablets were administered with 240 mL water after a fast of at least 10 hours.

    Investigational medicinal product name
    lamivudine
    Investigational medicinal product code
    Other name
    Epivir™
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Epivir™ (lamivudine) 150 mg tablets were administered with 240 mL water after a fast of at least 10 hours

    Investigational medicinal product name
    MK-0518B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MK-0518B 300 mg reformulated raltegravir / 150 mg lamivudine monolithic tablets were administered with 240 mL water after a fast of at least 10 hours.

    Number of subjects in period 1
    		Sequence 1: Isentress™ + Epivir™ then MK-0518B Sequence 2: MK-0518B then Isentress™ + Epivir™
    Started
    12
    12
    Completed
    12
    10
    Not completed
    0
    2
         Adverse event, non-fatal
    -
    1
         Protocol deviation
    -
    1
    Period 2
    Period 2 title
    Period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sequence 1: Isentress™ + Epivir™ then MK-0518B
    Arm description
    		 Participants received single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 1 then a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    raltegravir
    Investigational medicinal product code
    Other name
    Isentress(TM)
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Isentress™ (raltegravir) 400 mg tablets were administered with 240 mL water after a fast of at least 10 hours.

    Investigational medicinal product name
    lamivudine
    Investigational medicinal product code
    Other name
    Epivir(TM)
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Epivir™ (lamivudine) 150 mg tablets were administered with 240 mL water after a fast of at least 10 hours

    Investigational medicinal product name
    MK-0518B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MK-0518B 300 mg reformulated raltegravir / 150 mg lamivudine monolithic tablets were administered with 240 mL water after a fast of at least 10 hours.

    Arm title
    		 Sequence 2: MK-0518B then Isentress™ + Epivir™
    Arm description
    		 Participants received a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 1 then single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    raltegravir
    Investigational medicinal product code
    Other name
    Isentress(TM)
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Isentress™ (raltegravir) 400 mg tablets were administered with 240 mL water after a fast of at least 10 hours.

    Investigational medicinal product name
    lamivudine
    Investigational medicinal product code
    Other name
    Epivir(TM)
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Epivir™ (lamivudine) 150 mg tablets were administered with 240 mL water after a fast of at least 10 hours

    Investigational medicinal product name
    MK-0518B
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MK-0518B 300 mg reformulated raltegravir / 150 mg lamivudine monolithic tablets were administered with 240 mL water after a fast of at least 10 hours.

    Number of subjects in period 2
    		Sequence 1: Isentress™ + Epivir™ then MK-0518B Sequence 2: MK-0518B then Isentress™ + Epivir™
    Started
    12
    10
    Completed
    12
    10

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Period 1
    Reporting group description
    		 All participants who were enrolled in the study.

    Reporting group values
    		 Period 1 Total
    Number of subjects
    		 24 24
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36 ( 9 ) -
    Gender categorical
    Units: Subjects
        Female
    		 10 10
        Male
    		 14 14

    End points

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    End points reporting groups
    Reporting group title
    Sequence 1: Isentress™ + Epivir™ then MK-0518B
    Reporting group description
    		 Participants received single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 1 then a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 2.

    Reporting group title
    Sequence 2: MK-0518B then Isentress™ + Epivir™
    Reporting group description
    		 Participants received a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 1 then single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 2.
    Reporting group title
    Sequence 1: Isentress™ + Epivir™ then MK-0518B
    Reporting group description
    		 Participants received single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 1 then a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 2.

    Reporting group title
    Sequence 2: MK-0518B then Isentress™ + Epivir™
    Reporting group description
    		 Participants received a single dose of MK-0518B (300 mg raltegravir/150 mg lamivudine) in Period 1 then single doses of co-administered Isentress™ 400 mg and Epivir™ 150 mg in Period 2.

    Subject analysis set title
    Isentress™ + Epivir™
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who received Isentress™ + Epivir™ and completed the study.

    Subject analysis set title
    MK-0518B
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who received MK-0518B and completed the study.

    Primary: The area under the raltegravir concentration vs time curve from time zero to infinity (AUC0-∞)

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    End point title
    		 The area under the raltegravir concentration vs time curve from time zero to infinity (AUC0-∞)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Primary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng*h/mL
        geometric mean (confidence interval 95%)
    6756.58 (4815.4 to 9480.3)
    7210.2 (6221.15 to 8356.47)
    Statistical analysis title
    		 MK-0518B vs. Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    106.71
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 83.05
         upper limit
    		 137.11

    Primary: Maximum concentration (Cmax) of raltegravir

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    End point title
    		 Maximum concentration (Cmax) of raltegravir
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Primary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng/mL
        geometric mean (confidence interval 95%)
    1831.23 (1176.95 to 2849.21)
    2740.89 (2153.89 to 3487.85)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    149.68
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 105.86
         upper limit
    		 211.62

    Primary: The area under the lamivudine concentration vs time curve of from time zero to infinity (AUC0-∞)

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    End point title
    		 The area under the lamivudine concentration vs time curve of from time zero to infinity (AUC0-∞)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Primary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng*h/mL
        geometric mean (confidence interval 95%)
    5879.3 (5421.8 to 6375.4)
    6107.2 (5652.1 to 6598.9)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    103.88
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 97.64
         upper limit
    		 110.51

    Primary: Maximum concentration (Cmax) of lamivudine

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    End point title
    		 Maximum concentration (Cmax) of lamivudine
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Primary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng/mL
        geometric mean (confidence interval 95%)
    1205.7 (1057.6 to 1374.4)
    1362.1 (1188.9 to 1560.6)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    112.98
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 102.3
         upper limit
    		 124.77

    Secondary: The area under the raltegravir concentration vs time curve of from time zero to the last sampling time with quantifiable analyte (AUC0-t)

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    End point title
    		 The area under the raltegravir concentration vs time curve of from time zero to the last sampling time with quantifiable analyte (AUC0-t)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Secondary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng*h/mL
        geometric mean (confidence interval 95%)
    6565.66 (4652.46 to 9265.61)
    7061.36 (6094.57 to 8181.5)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    107.55
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 82.91
         upper limit
    		 139.5

    Secondary: Concentration of raltegravir at time 12 hours (C12)

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    End point title
    		 Concentration of raltegravir at time 12 hours (C12)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Secondary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng/mL
        geometric mean (confidence interval 95%)
    28.04 (22.81 to 34.47)
    25.41 (20.77 to 31.1)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    90.63
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 76.9
         upper limit
    		 106.81

    Secondary: The area under the lamivudine concentration vs time curve from time zero to the last sampling time with quantifiable analyte (AUC0-t)

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    End point title
    		 The area under the lamivudine concentration vs time curve from time zero to the last sampling time with quantifiable analyte (AUC0-t)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose.
    End point type
    Secondary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng*h/mL
        geometric mean (confidence interval 95%)
    5655.4 (5182.1 to 6171.9)
    6019 (5423.2 to 6680.2)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 Geometric mean ratio
    Point estimate
    106.43
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 99.77
         upper limit
    		 113.53

    Secondary: Concentration of lamivudine at time 12 hours (C12)

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    End point title
    		 Concentration of lamivudine at time 12 hours (C12)
    End point description
    Blood samples for analysis of pharmacokinetic parameters were collected prior to dosing and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point type
    Secondary
    End point timeframe
    Predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
    End point values
    		 Isentress™ + Epivir™ MK-0518B
    Number of subjects analysed
    22
    24
    Units: ng/mL
        geometric mean (confidence interval 95%)
    68.7 (59.7 to 79)
    70.6 (61.7 to 80.8)
    Statistical analysis title
    		 MK-0518B vs Isentress™ + Epivir™
    Statistical analysis description
    Treatment differences were compared using a linear mixed effect model containing period and treatment as fixed effects. An unstructured covariance matrix was used to allow for unequal treatment variances and to model the correlation between the two treatment measurements within each subject. The same participants and number (n=24) were to have received both treatments but due to dropouts, n=24 received MK-0518B and n=22 received Isentress™ + Epivir™. GMR = (MK-0518B/Isentress™ + Epivir™)
    Comparison groups
    Isentress™ + Epivir™ v MK-0518B
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    		 Mixed models analysis
    Parameter type
    		 geometric mean ratio
    Point estimate
    102.89
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 97.76
         upper limit
    		 108.28

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Predose to 14 days following the last dose of study drug (approximately 20 days).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    Isentress™ + Epivir™
    Reporting group description
    		 -

    Reporting group title
    MK-0518B
    Reporting group description
    		 -

    Serious adverse events
    		 Isentress™ + Epivir™ MK-0518B
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 22 (0.00%)
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Isentress™ + Epivir™ MK-0518B
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 22 (18.18%)
    3 / 24 (12.50%)
    Investigations
    Blood Glucose Increased
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Blood creatine increased
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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