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   43851   clinical trials with a EudraCT protocol, of which   7283   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 Study of the Comparative Bioavailability of Two Investigational Pediatric Oral Granule Formulations of Lamivudine and Tenofovir Compared to the Adult Marketed Formulations

    Summary
    EudraCT number
    		 2016-004392-41
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    25 Jan 2017

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    1439a-054
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Protocol Number: MK-1439A-054
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, Kenilworth, NJ,
    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-001695-PIP01-14
    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 Jan 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Dec 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study was to compare the bioavailability of pediatric formulations with the adult marketed formulations of lamivudine and tenofovir disoproxil fumarate (TDF) administered as single, oral doses to adult healthy males and females.
    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
    16 Nov 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    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
    		 Healthy, non-smoking, males and females, from 18 to 55 years of age were enrolled in this study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 All Enrolled Participants
    Arm description
    		 The 14 treatments were as follows: 1) one lamivudine tablet followed by one tenofovir (TDF) tablet; 2) 60 lamivudine uncoated granules (UG) followed by 60 TDF UG; 3) 60 lamivudine coated OG (CG) followed by 60 TDF CG; 4) one TDF tablet followed by one lamivudine tablet; 5) 60 TDF UG followed by 60 lamivudine UG; 6) 60 TDF CG followed by 60 lamivudine CG; 7) 60 lamivudine UG in vanilla pudding (VP) followed by 60 TDF UG in VP; 8) 60 lamivudine UG in applesauce (AS) followed by 60 TDF UG in AS; 9) 60 lamivudine CG in VP followed by 60 TDF CG in VP; 10) 60 lamivudine CG in AS followed by 60 TDF CG in AS; 11) 60 TDF UG in VP followed by 60 lamivudine UG in VP; 12) 60 TDF pediatric UG in AS followed by 60 lamivudine UG in AS; 13) 60 TDF CG in VP followed by 60 lamivudine CG in VP; 14) 60 TDF CG in AS followed by 60 lamivudine CG in AS.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lamivudine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single oral dose of 300 mg of lamivudine adult oral tablets or 60 pediatric x 5-mg uncoated or coated oral granules (administered alone, with vanilla pudding, or with applesauce).

    Investigational medicinal product name
    Tenofovir disoproxil fumarate
    Investigational medicinal product code
    Other name
    TDF
    Pharmaceutical forms
    Granules, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    A single oral dose of 300 mg of lamivudine adult oral tablets or 60 pediatric x 5-mg uncoated or coated oral granules (administered alone, with vanilla pudding, or with applesauce).

    Number of subjects in period 1
    		All Enrolled Participants
    Started
    24
    Completed
    22
    Not completed
    2
         Adverse event, non-fatal
    1
         Non-compliance with protocol restrictions
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 All Enrolled Participants

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 24 24
    Age Categorical
    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)
    		 24 24
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 39.0 ± 8.6 -
    Gender Categorical
    Units: Subjects
        Female
    		 19 19
        Male
    		 5 5

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    All Enrolled Participants
    Reporting group description
    		 The 14 treatments were as follows: 1) one lamivudine tablet followed by one tenofovir (TDF) tablet; 2) 60 lamivudine uncoated granules (UG) followed by 60 TDF UG; 3) 60 lamivudine coated OG (CG) followed by 60 TDF CG; 4) one TDF tablet followed by one lamivudine tablet; 5) 60 TDF UG followed by 60 lamivudine UG; 6) 60 TDF CG followed by 60 lamivudine CG; 7) 60 lamivudine UG in vanilla pudding (VP) followed by 60 TDF UG in VP; 8) 60 lamivudine UG in applesauce (AS) followed by 60 TDF UG in AS; 9) 60 lamivudine CG in VP followed by 60 TDF CG in VP; 10) 60 lamivudine CG in AS followed by 60 TDF CG in AS; 11) 60 TDF UG in VP followed by 60 lamivudine UG in VP; 12) 60 TDF pediatric UG in AS followed by 60 lamivudine UG in AS; 13) 60 TDF CG in VP followed by 60 lamivudine CG in VP; 14) 60 TDF CG in AS followed by 60 lamivudine CG in AS.

    Subject analysis set title
    300 mg lamivudine adult tablet + tenofovir
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine adult tablet followed by a single oral dose of 300 mg tenofovir adult tablet

    Subject analysis set title
    300 mg lamivudine uncoated granules + tenofovir
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules followed by a single oral dose of 300 mg tenofovir pediatric uncoated granules

    Subject analysis set title
    300 mg lamivudine coated granules + tenofovir
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules followed by a single oral dose of 300 mg tenofovir pediatric coated oral granules

    Subject analysis set title
    300 mg tenofovir adult tablet + lamivudine
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir adult tablet followed by a single oral dose of 300 mg lamivudine adult tablet

    Subject analysis set title
    300 mg tenofovir uncoated granules + lamivudine
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric uncoated granules followed by a single oral dose of 300 mg lamivudine pediatric uncoated granules

    Subject analysis set title
    300 mg tenofovir coated granules + lamivudine
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric coated granules followed by a single oral dose of 300 mg lamivudine pediatric coated granules

    Subject analysis set title
    300 mg lamivudine uncoated granules + tenofovir in pudding
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules followed by a single oral dose of 300 mg tenofovir pediatric uncoated granules in pudding

    Subject analysis set title
    300 mg lamivudine uncoated granules + tenofovir in applesauce
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules followed by a single oral dose of 300 mg tenofovir pediatric uncoated granules in applesauce

    Subject analysis set title
    300 mg tenofovir uncoated granules + lamivudine in pudding
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric uncoated granules followed by a single oral dose of 300 mg lamivudine pediatric uncoated granules in pudding

    Subject analysis set title
    300 mg tenofovir uncoated granules + lamivudine in applesauce
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric uncoated granules followed by a single oral dose of 300 mg lamivudine pediatric uncoated granules in applesauce

    Subject analysis set title
    300 mg lamivudine coated granules + tenofovir in pudding
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules followed by a single oral dose of 300 mg tenofovir pediatric coated granules in pudding

    Subject analysis set title
    300 mg lamivudine coated granules + tenofovir in applesauce
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules followed by a single oral dose of 300 mg tenofovir pediatric coated granules in applesauce

    Subject analysis set title
    300 mg tenofovir coated granules + lamivudine in pudding
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric coated granules followed by a single oral dose of 300 mg lamivudine pediatric coated granules in pudding

    Subject analysis set title
    300 mg tenofovir coated granules + lamivudine in applesauce
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Under fasted conditions a single oral dose of 300 mg tenofovir pediatric coated granules followed by a single oral dose of 300 mg lamivudine pediatric coated granules in applesauce

    Primary: Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of plasma lamivudine

    		 Close Top of page
    End point title
    		 Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of plasma lamivudine
    End point description
    Participants were treated with a single oral dose of 300 mg lamivudine with 300 mg of tenofovir. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the AUC0-inf of plasma lamivudine. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg lamivudine adult tablet + tenofovir 300 mg lamivudine uncoated granules + tenofovir 300 mg lamivudine coated granules + tenofovir 300 mg lamivudine uncoated granules + tenofovir in pudding 300 mg lamivudine uncoated granules + tenofovir in applesauce 300 mg lamivudine coated granules + tenofovir in pudding 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    9
    10
    Units: hr*ng/mL
        geometric mean (confidence interval 95%)
    14100 (13200 to 15100)
    14100 (13400 to 14800)
    14100 (13400 to 14800)
    11000 (10200 to 12000)
    11100 (10200 to 12100)
    11900 (10500 to 13400)
    12200 (11400 to 13000)
    Statistical analysis title
    		 Lamivudine: Uncoated Granules / Adult Tablet
    Statistical analysis description
    Geometric mean ratio (GMR) of 300 mg lamivudine uncoated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine adult tablet + tenofovir
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    Method
    Parameter type
    		 GMR
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.03
    Notes
    [1] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine coated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine coated granules + tenofovir
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    Method
    Parameter type
    		 GMR
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.03
    Notes
    [2] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.78
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.83
    Notes
    [3] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Uncoated Granules:Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [4]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.79
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 0.83
    Notes
    [4] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in pudding
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.78
         upper limit
    		 0.92
    Notes
    [5] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [6]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.86
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 0.91
    Notes
    [6] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: AUC0-inf of plasma tenofovir

    		 Close Top of page
    End point title
    		 AUC0-inf of plasma tenofovir
    End point description
    Participants were treated with a single oral dose of 300 mg tenofovir with 300 mg of lamivudine. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the AUC0-inf of plasma tenofovir. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg tenofovir adult tablet + lamivudine 300 mg tenofovir uncoated granules + lamivudine 300 mg tenofovir coated granules + lamivudine 300 mg tenofovir uncoated granules + lamivudine in pudding 300 mg tenofovir uncoated granules + lamivudine in applesauce 300 mg tenofovir coated granules + lamivudine in pudding 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: hr*ng/mL
        geometric mean (confidence interval 95%)
    2800 (2450 to 3210)
    2910 (2700 to 3150)
    2920 (2680 to 3180)
    3300 (2900 to 3760)
    3490 (2960 to 4130)
    3450 (3180 to 3730)
    3360 (3050 to 3710)
    Statistical analysis title
    		 Tenofovir: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir uncoated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir uncoated granules + lamivudine
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.12
    Notes
    [7] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir coated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir coated granules + lamivudine
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [8]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.13
    Notes
    [8] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [9]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.23
    Notes
    [9] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [10]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 1.34
    Notes
    [10] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [11]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.18
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 1.25
    Notes
    [11] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [12]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.15
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 1.23
    Notes
    [12] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: Area under the concentration-time curve from time 0 to the last time point (AUC0-last) of plasma lamivudine

    		 Close Top of page
    End point title
    		 Area under the concentration-time curve from time 0 to the last time point (AUC0-last) of plasma lamivudine
    End point description
    Participants were treated with a single oral dose of 300 mg lamivudine with 300 mg of tenofovir. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the AUC0-last of plasma lamivudine. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg lamivudine adult tablet + tenofovir 300 mg lamivudine uncoated granules + tenofovir 300 mg lamivudine coated granules + tenofovir 300 mg lamivudine uncoated granules + tenofovir in pudding 300 mg lamivudine uncoated granules + tenofovir in applesauce 300 mg lamivudine coated granules + tenofovir in pudding 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: hr*ng/mL
        geometric mean (confidence interval 95%)
    14000 (13100 to 14900)
    13900 (13200 to 14600)
    13900 (13100 to 14600)
    10900 (9960 to 11800)
    10900 (10000 to 11900)
    11700 (10300 to 13200)
    11700 (10900 to 12500)
    Statistical analysis title
    		 Lamivudine: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine uncoated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine uncoated granules + tenofovir
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [13]
    Method
    Parameter type
    		 GMR
    Point estimate
    1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.04
    Notes
    [13] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine coated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine coated granules + tenofovir
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [14]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.99
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.03
    Notes
    [14] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [15]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.78
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.83
    Notes
    [15] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Uncoated Granules:Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [16]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.78
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.83
    Notes
    [16] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [17]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 0.91
    Notes
    [17] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [18]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 0.88
    Notes
    [18] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: AUC0-last of plasma tenofovir

    		 Close Top of page
    End point title
    		 AUC0-last of plasma tenofovir
    End point description
    Participants were treated with a single oral dose of 300 mg tenofovir with 300 mg of lamivudine. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the AUC0-last of plasma tenofovir. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg tenofovir adult tablet + lamivudine 300 mg tenofovir uncoated granules + lamivudine 300 mg tenofovir coated granules + lamivudine 300 mg tenofovir uncoated granules + lamivudine in pudding 300 mg tenofovir uncoated granules + lamivudine in applesauce 300 mg tenofovir coated granules + lamivudine in pudding 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: hr*ng/mL
        geometric mean (confidence interval 95%)
    2640 (2310 to 3020)
    2740 (2540 to 2960)
    2740 (2530 to 2980)
    3100 (2730 to 3500)
    3250 (2750 to 3850)
    3240 (3000 to 3500)
    3140 (2860 to 3440)
    Statistical analysis title
    		 Tenofovir: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir uncoated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir uncoated granules + lamivudine
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [19]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.13
    Notes
    [19] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir coated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir coated granules + lamivudine
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [20]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.12
    Notes
    [20] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [21]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.22
    Notes
    [21] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [22]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.19
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 1.33
    Notes
    [22] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [23]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.18
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 1.25
    Notes
    [23] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [24]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.14
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 1.22
    Notes
    [24] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: Maximum concentration (Cmax) of plasma lamivudine

    		 Close Top of page
    End point title
    		 Maximum concentration (Cmax) of plasma lamivudine
    End point description
    Participants were treated with a single oral dose of 300 mg lamivudine with 300 mg of tenofovir. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the Cmax of plasma lamivudine. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg lamivudine adult tablet + tenofovir 300 mg lamivudine uncoated granules + tenofovir 300 mg lamivudine coated granules + tenofovir 300 mg lamivudine uncoated granules + tenofovir in pudding 300 mg lamivudine uncoated granules + tenofovir in applesauce 300 mg lamivudine coated granules + tenofovir in pudding 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: ng/mL
        geometric mean (confidence interval 95%)
    2990 (2600 to 3430)
    3120 (2810 to 3460)
    2970 (2610 to 3380)
    2330 (2100 to 2590)
    2540 (2240 to 2870)
    2510 (2120 to 2960)
    2500 (2060 to 3030)
    Statistical analysis title
    		 Lamivudine: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine uncoated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine uncoated granules + tenofovir
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [25]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.13
    Notes
    [25] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine coated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine coated granules + tenofovir
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [26]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.99
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.08
    Notes
    [26] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [27]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.75
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 0.81
    Notes
    [27] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Uncoated Granules:Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [28]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.81
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 0.89
    Notes
    [28] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [29]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 0.95
    Notes
    [29] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [30]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.84
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 0.96
    Notes
    [30] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: Cmax of plasma tenofovir

    		 Close Top of page
    End point title
    		 Cmax of plasma tenofovir
    End point description
    Participants were treated with a single oral dose of 300 mg tenofovir with 300 mg of lamivudine. Blood samples collected from pre-dose (0-hr) up to 72 hours post-dose were used to determine the Cmax of plasma tenofovir. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    Pre-dose (0-hr), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, 48, and 72 hours post-dose
    End point values
    		 300 mg tenofovir adult tablet + lamivudine 300 mg tenofovir uncoated granules + lamivudine 300 mg tenofovir coated granules + lamivudine 300 mg tenofovir uncoated granules + lamivudine in pudding 300 mg tenofovir uncoated granules + lamivudine in applesauce 300 mg tenofovir coated granules + lamivudine in pudding 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: ng/mL
        geometric mean (confidence interval 95%)
    311 (270 to 358)
    322 (292 to 355)
    321 (288 to 357)
    392 (343 to 448)
    395 (321 to 486)
    394 (352 to 441)
    384 (336 to 439)
    Statistical analysis title
    		 Tenofovir: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir uncoated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir uncoated granules + lamivudine
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [31]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.14
    Notes
    [31] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir coated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir coated granules + lamivudine
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [32]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.03
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 1.14
    Notes
    [32] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [33]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.22
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 1.35
    Notes
    [33] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [34]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.23
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 1.43
    Notes
    [34] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [35]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.23
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.12
         upper limit
    		 1.35
    Notes
    [35] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 1.33
    Notes
    [36] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: Concentration at 24 hours post-dose (C24) of plasma lamivudine

    		 Close Top of page
    End point title
    		 Concentration at 24 hours post-dose (C24) of plasma lamivudine
    End point description
    Participants were treated with a single oral dose of 300 mg lamivudine with 300 mg of tenofovir. Blood samples collected at 24 hours post-dose were used to determine the C24 of plasma lamivudine. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    24 hours post-dose
    End point values
    		 300 mg lamivudine adult tablet + tenofovir 300 mg lamivudine uncoated granules + tenofovir 300 mg lamivudine coated granules + tenofovir 300 mg lamivudine uncoated granules + tenofovir in pudding 300 mg lamivudine uncoated granules + tenofovir in applesauce 300 mg lamivudine coated granules + tenofovir in pudding 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: ng/mL
        geometric mean (confidence interval 95%)
    31.9 (28.9 to 35.2)
    30.7 (28.1 to 33.6)
    32.1 (29.1 to 35.5)
    36.9 (32.0 to 42.5)
    34.2 (27.0 to 43.4)
    33.3 (29.9 to 37.0)
    33.2 (30.0 to 36.7)
    Statistical analysis title
    		 Lamivudine: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine uncoated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine uncoated granules + tenofovir
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [37]
    Method
    Parameter type
    		 GMR
    Point estimate
    0.96
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.91
         upper limit
    		 1.02
    Notes
    [37] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg lamivudine coated granules with tenofovir / 300 mg lamivudine adult tablet with tenofovir
    Comparison groups
    300 mg lamivudine adult tablet + tenofovir v 300 mg lamivudine coated granules + tenofovir
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [38]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.01
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.07
    Notes
    [38] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [39]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.09
         upper limit
    		 1.32
    Notes
    [39] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Uncoated Granules:Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine uncoated granules + tenofovir v 300 mg lamivudine uncoated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [40]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.11
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.31
    Notes
    [40] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in pudding / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [41]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.12
    Notes
    [41] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Lamivudine Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg lamivudine with tenofovir dosed in applesauce / 300 mg lamivudine with tenofovir dosed alone
    Comparison groups
    300 mg lamivudine coated granules + tenofovir v 300 mg lamivudine coated granules + tenofovir in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [42]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.03
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.11
    Notes
    [42] - The same participants took both treatments; so the number analyzed is actually 24.

    Primary: C24 of plasma tenofovir

    		 Close Top of page
    End point title
    		 C24 of plasma tenofovir
    End point description
    Participants were treated with a single oral dose of 300 mg tenofovir with 300 mg of lamivudine. Blood samples collected at 24 hours post-dose were used to determine the C24 of plasma tenofovir. Plasma concentrations were natural log transformed, and a linear mixed effects model was used to generate back-transformed least square means and confidence intervals.
    End point type
    Primary
    End point timeframe
    24 hours post-dose
    End point values
    		 300 mg tenofovir adult tablet + lamivudine 300 mg tenofovir uncoated granules + lamivudine 300 mg tenofovir coated granules + lamivudine 300 mg tenofovir uncoated granules + lamivudine in pudding 300 mg tenofovir uncoated granules + lamivudine in applesauce 300 mg tenofovir coated granules + lamivudine in pudding 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects analysed
    24
    23
    24
    12
    12
    10
    11
    Units: ng/mL
        geometric mean (confidence interval 95%)
    32.8 (28.4 to 37.9)
    34.2 (31.7 to 37.0)
    34.1 (31.6 to 36.7)
    38.1 (33.7 to 42.9)
    40.5 (34.9 to 46.9)
    40.9 (37.7 to 44.5)
    38.5 (35.2 to 42.2)
    Statistical analysis title
    		 Tenofovir: Uncoated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir uncoated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir uncoated granules + lamivudine
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other [43]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.15
    Notes
    [43] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir: Coated Granules / Adult Tablet
    Statistical analysis description
    GMR of 300 mg tenofovir coated granules with lamivudine / 300 mg tenofovir adult tablet with lamivudine
    Comparison groups
    300 mg tenofovir adult tablet + lamivudine v 300 mg tenofovir coated granules + lamivudine
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other [44]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.14
    Notes
    [44] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in pudding
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [45]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.11
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 1.21
    Notes
    [45] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Uncoated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir uncoated granules + lamivudine v 300 mg tenofovir uncoated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [46]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.18
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.07
         upper limit
    		 1.31
    Notes
    [46] - The same participants took both treatments; so the number analyzed is actually 23.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Pudding / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in pudding / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in pudding
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 other [47]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.13
         upper limit
    		 1.28
    Notes
    [47] - The same participants took both treatments; so the number analyzed is actually 24.
    Statistical analysis title
    		 Tenofovir Coated Granules: In Applesauce / Alone
    Statistical analysis description
    GMR of 300 mg tenofovir with lamivudine dosed in applesauce / 300 mg tenofovir with lamivudine dosed alone
    Comparison groups
    300 mg tenofovir coated granules + lamivudine v 300 mg tenofovir coated granules + lamivudine in applesauce
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other [48]
    Method
    Parameter type
    		 GMR
    Point estimate
    1.13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.06
         upper limit
    		 1.21
    Notes
    [48] - The same participants took both treatments; so the number analyzed is actually 24.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to 7 days after each study treatment, and up to 14 days after the last treatment.
    Adverse event reporting additional description
    All participants who received at least one dose of investigational drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Lamivudine 300 mg tablet + Tenofovir 300 mg tablet
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine adult tablet with a single oral dose of 300 mg tenofovir adult tablet

    Reporting group title
    Lamivudine 300 mg uncoated granules (UG) + Tenofovir 300 mg UG
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules with a single oral dose of 300 mg tenofovir pediatric uncoated granules

    Reporting group title
    Lamivudine 300 mg coated granules (CG) + Tenofovir 300 mg CG
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules with a single oral dose of 300 mg tenofovir pediatric coated granules

    Reporting group title
    Lamivudine 300 mg UG + Tenofovir 300 mg UG, with pudding
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules with a single oral dose of 300 mg tenofovir pediatric uncoated granules, with pudding

    Reporting group title
    Lamivudine 300 mg UG + Tenofovir 300 mg UG, with applesauce
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric uncoated granules with a single oral dose of 300 mg tenofovir pediatric uncoated granules, with applesauce

    Reporting group title
    Lamivudine 300 mg CG + Tenofovir 300 mg CG, with pudding
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules with a single oral dose of 300 mg tenofovir pediatric coated granules, with pudding

    Reporting group title
    Lamivudine 300 mg CG + Tenofovir 300 mg CG, with applesauce
    Reporting group description
    		 Under fasted conditions a single oral dose of 300 mg lamivudine pediatric coated granules with a single oral dose of 300 mg tenofovir pediatric coated granules, with applesauce

    Serious adverse events
    		 Lamivudine 300 mg tablet + Tenofovir 300 mg tablet Lamivudine 300 mg uncoated granules (UG) + Tenofovir 300 mg UG Lamivudine 300 mg coated granules (CG) + Tenofovir 300 mg CG Lamivudine 300 mg UG + Tenofovir 300 mg UG, with pudding Lamivudine 300 mg UG + Tenofovir 300 mg UG, with applesauce Lamivudine 300 mg CG + Tenofovir 300 mg CG, with pudding Lamivudine 300 mg CG + Tenofovir 300 mg CG, with applesauce
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Lamivudine 300 mg tablet + Tenofovir 300 mg tablet Lamivudine 300 mg uncoated granules (UG) + Tenofovir 300 mg UG Lamivudine 300 mg coated granules (CG) + Tenofovir 300 mg CG Lamivudine 300 mg UG + Tenofovir 300 mg UG, with pudding Lamivudine 300 mg UG + Tenofovir 300 mg UG, with applesauce Lamivudine 300 mg CG + Tenofovir 300 mg CG, with pudding Lamivudine 300 mg CG + Tenofovir 300 mg CG, with applesauce
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 24 (25.00%)
    3 / 23 (13.04%)
    5 / 24 (20.83%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
    2 / 10 (20.00%)
    3 / 11 (27.27%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    Nervous system disorders
    Head discomfort
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Headache
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    2
    1
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    4 / 24 (16.67%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    2 / 11 (18.18%)
         occurrences all number
    1
    0
    4
    0
    0
    1
    2
    General disorders and administration site conditions
    Catheter site related reaction
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    2 / 24 (8.33%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    2
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 10 (10.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Initial insomnia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 10 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Nov 2016
    Amendment 1: Clarifications for Test Procedures, Drug Administration, and Palatability Questions.

    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-Sat Apr 20 11:24:44 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA