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   43861   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1, Single-Dose, Cross-Over Study Evaluating the Relative Bioavailability of a Pediatric Oral Granule Formulation of Tenofovir Alafenamide in Healthy Adults

    Summary
    EudraCT number
    		 2019-003269-16
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    19 Oct 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Oct 2020
    First version publication date
    24 Oct 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-320-1196
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001584-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
    19 Oct 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Oct 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the relative bioavailability of a pediatric oral granule formulation of tenofovir alafenamide (TAF) relative to the adult tablet formulation in healthy participants.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Aug 2019
    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
    United States: 37
    Worldwide total number of subjects
    37
    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)
    37
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at a study site in the United States. The first participant was screened on 12 Aug 2019. The last study visit occurred on 19 Oct 2019.

    Pre-assignment
    Screening details
    		 93 participants were screened.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 TAF 25 mg (Treatment Sequence: Tablet- Granule)
    Arm description
    		 Participants received single oral dose of tenofovir alafenamide (TAF) 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir alafenamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg administered on Day 1 in treatment period 1.

    Investigational medicinal product name
    Tenofovir alafenamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg administered on Day 13 in treatment period 2.

    Arm title
    		 TAF 25 mg (Treatment Sequence: Granule-Tablet)
    Arm description
    		 Participants received single oral dose of TAF 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of TAF 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir alafenamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg administered on Day 1 in treatment period 1.

    Investigational medicinal product name
    Tenofovir alafenamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg administered on Day 13 in treatment period 2.

    Number of subjects in period 1
    		TAF 25 mg (Treatment Sequence: Tablet- Granule) TAF 25 mg (Treatment Sequence: Granule-Tablet)
    Started
    18
    19
    Completed
    18
    18
    Not completed
    0
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    TAF 25 mg (Treatment Sequence: Tablet- Granule)
    Reporting group description
    		 Participants received single oral dose of tenofovir alafenamide (TAF) 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.

    Reporting group title
    TAF 25 mg (Treatment Sequence: Granule-Tablet)
    Reporting group description
    		 Participants received single oral dose of TAF 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of TAF 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.

    Reporting group values
    		 TAF 25 mg (Treatment Sequence: Tablet- Granule) TAF 25 mg (Treatment Sequence: Granule-Tablet) Total
    Number of subjects
    		 18 19 37
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 32 ( 6.5 ) 34 ( 6.3 ) -
    Gender categorical
    Units: Subjects
        Female
    		 8 6 14
        Male
    		 10 13 23

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    TAF 25 mg (Treatment Sequence: Tablet- Granule)
    Reporting group description
    		 Participants received single oral dose of tenofovir alafenamide (TAF) 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.

    Reporting group title
    TAF 25 mg (Treatment Sequence: Granule-Tablet)
    Reporting group description
    		 Participants received single oral dose of TAF 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 1 in treatment period 1 followed by single oral dose of TAF 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 13 in treatment period 2. Each treatment period was separated by a washout period of 11 days.

    Subject analysis set title
    TAF Tablet
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received single oral dose of TAF 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 1 in treatment period 1 or on Day 13 in treatment period 2.

    Subject analysis set title
    TAF Granule
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants received single oral dose of TAF 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 1 in treatment period 1 or on Day 13 in treatment period 2.

    Primary: Pharmacokinetic (PK) Parameter: AUClast of TAF and its Metabolite tenofovir (TFV)

    		 Close Top of page
    End point title
    		 Pharmacokinetic (PK) Parameter: AUClast of TAF and its Metabolite tenofovir (TFV)
    End point description
    AUClast is defined as the concentration of drug from time zero to the last observable concentration. Participants in the PK Analysis Set (included all randomized participants who took at least 1 dose of study drug and had at least 1 non-missing concentration value reported by the PK laboratory for each respective analyte) with available data were analysed.
    End point type
    Primary
    End point timeframe
    Predose (≤ 5 minutes), 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours postdose on Day 1 and Day 13
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: hours*nanograms per milliter (h*ng/mL)
    arithmetic mean (standard deviation)
        TAF
    196.9 ( 71.30 )
    208.9 ( 55.77 )
        TFV
    226.3 ( 33.48 )
    235.4 ( 38.52 )
    Statistical analysis title
    		 TAF: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    109.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 100.93
         upper limit
    		 119.45
    Statistical analysis title
    		 TFV: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    104.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 100.34
         upper limit
    		 108

    Primary: PK Parameter: AUCinf of TAF and its Metabolite TFV

    		 Close Top of page
    End point title
    		 PK Parameter: AUCinf of TAF and its Metabolite TFV
    End point description
    AUCinf is defined as the concentration of drug extrapolated to infinite time. Participants in the PK Analysis Set with the available data were analyzed.
    End point type
    Primary
    End point timeframe
    Predose (≤ 5 minutes), 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours postdose on Day 1 and Day 13
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        TAF
    198.8 ( 70.71 )
    211.7 ( 55.14 )
        TFV
    260.8 ( 38.04 )
    270.7 ( 43.05 )
    Statistical analysis title
    		 TAF: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    109.99
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 101.28
         upper limit
    		 119.45
    Statistical analysis title
    		 TFV: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    103.91
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 100.25
         upper limit
    		 107.71

    Primary: PK Parameter: Cmax of TAF and its Metabolite TFV

    		 Close Top of page
    End point title
    		 PK Parameter: Cmax of TAF and its Metabolite TFV
    End point description
    Cmax is defined as the maximum concentration of drug. Participants in the PK Analysis Set with the available data were analyzed.
    End point type
    Primary
    End point timeframe
    Predose (≤ 5 minutes), 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours postdose on Day 1 and Day 13
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: nanograms/milliliters (ng/mL)
    arithmetic mean (standard deviation)
        TAF
    151.2 ( 96.52 )
    125.4 ( 46.97 )
        TFV
    6.3 ( 1.13 )
    6.1 ( 0.99 )
    Statistical analysis title
    		 TAF: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    95.25
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 80.83
         upper limit
    		 112.24
    Statistical analysis title
    		 TFV: TAF Tablet vs TAF Granule
    Statistical analysis description
    Subjects included in this analysis states 73; however, only 37 unique participants were analyzed for Treatment TAF Tablet and Treatment TAF Granule.
    Comparison groups
    TAF Tablet v TAF Granule
    Number of subjects included in analysis
    73
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    Method
    Parameter type
    		 % Geometric Least Square Mean Ratio
    Point estimate
    97.54
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 92.59
         upper limit
    		 102.77

    Secondary: PK Parameter: Tmax of TAF and its Metabolite TFV

    		 Close Top of page
    End point title
    		 PK Parameter: Tmax of TAF and its Metabolite TFV
    End point description
    Tmax is defined as the time (observed time point) of Cmax. Participants in the PK Analysis Set with the available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Predose (≤ 5 minutes), 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours postdose on Day 1 and Day 13
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: hours
    median (full range (min-max))
        TAF
    1.25 (0.50 to 4.00)
    1.00 (0.25 to 3.00)
        TFV
    3.00 (1.50 to 6.00)
    3.00 (1.50 to 5.00)
    No statistical analyses for this end point

    Secondary: PK Parameter: t1/2 of TAF and its Metabolite TFV

    		 Close Top of page
    End point title
    		 PK Parameter: t1/2 of TAF and its Metabolite TFV
    End point description
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Participants in the PK Analysis Set with the available data were analyzed.
    End point type
    Secondary
    End point timeframe
    Predose (≤5 minutes), 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours postdose on Day 1 and Day 13
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: hours
    arithmetic mean (standard deviation)
        TAF
    0.54 ( 0.252 )
    0.69 ( 0.318 )
        TFV
    51.84 ( 9.305 )
    51.33 ( 10.248 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    		 Close Top of page
    End point title
    		 Percentage of Participants Experiencing Treatment-Emergent Adverse Events
    End point description
    Participants in the Safety Analysis Set (included all randomized participants who took at least 1 dose of study drug) with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    From first dose up to Day 13 plus 30 days
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: percentage of participants
        number (not applicable)
    11.1
    24.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities

    		 Close Top of page
    End point title
    		 Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities
    End point description
    Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant. Participants in the Safety Analysis Set with available data were analyzed.
    End point type
    Secondary
    End point timeframe
    From first dose up to Day 13 plus 30 days
    End point values
    		 TAF Tablet TAF Granule
    Number of subjects analysed
    36
    37
    Units: percentage of participants
    number (not applicable)
        Any Grade 1 or above
    33.3
    24.3
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose up to Day 13 plus 30 days
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    TAF Tablet
    Reporting group description
    		 Participants who received single oral dose of TAF 25 mg adult tablet (1 X 25 mg) under fed conditions on Day 1 in treatment period 1 or on Day 13 in treatment period 2 were analyzed.

    Reporting group title
    TAF Granule
    Reporting group description
    		 Participants who received single oral dose of TAF 25 mg pediatric granule formulation (2 X 12.5 mg) under fed conditions on Day 1 in treatment period 1 or on Day 13 in treatment period 2 were analyzed.

    Serious adverse events
    		 TAF Tablet TAF Granule
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 37 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 TAF Tablet TAF Granule
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 36 (5.56%)
    4 / 37 (10.81%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 36 (5.56%)
    2 / 37 (5.41%)
         occurrences all number
    2
    2
    Somnolence
         subjects affected / exposed
    0 / 36 (0.00%)
    2 / 37 (5.41%)
         occurrences all number
    0
    2

    More information

    		 Close Top of page

    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
    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-Thu Apr 25 23:01:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA