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    Clinical Trial Results:
    A Phase I, open-label, randomized, 3-panel, 3-way crossover trial in healthy adult subjects to assess the relative bioavailability of TMC435 following administration of 2 liquid formulations or 2 different capsule concept formulations compared to the Phase III 150 mg capsule, and to assess the effect of food on the bioavailability of TMC435 following administration of the liquid formulations

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2011-005808-14
    Trial protocol
    GB  
    Global end of trial date
    29 May 2012

    Results information
    Results version number
    v2(current)
    This version publication date
    16 Jul 2016
    First version publication date
    02 Aug 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Review of data

    Trial information

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    Trial identification
    Sponsor protocol code
    TMC435HPC1002
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01571570
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Sciences Ireland
    Sponsor organisation address
    East gate Village, East gate, Little Island, Co. Cork, Ireland,
    Public contact
    Janssen Sciences Ireland, Clinical Registry Group, 353 214673500, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Janssen Sciences Ireland, Clinical Registry Group, 353 214673500, ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 May 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 May 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this study was to compare the rate and extent of absorption of a single 150 milligrams (mg) dose of 2 different liquid formulations of TMC435 to that of a single dose of the Phase III 150 mg capsule, after a high-fat breakfast in healthy adult subjects, to compare the rate and extent of absorption of a single 150 mg dose of 2 different liquid formulations of TMC435 in the fed (high-fat) and fasted state in healthy adult subjects and to compare the rate and extent of absorption of a single 150 mg dose of 2 different capsule concept formulations of TMC435 to that of a single dose of the Phase III 150 mg capsule, after a high-fat breakfast in healthy adult participants.
    Protection of trial subjects
    The safety assessments included adverse events (AEs), electrocardiogram (ECG), clinical laboratory tests, physical examination and vital sign were monitored throughout the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    03 Mar 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 72
    Worldwide total number of subjects
    72
    EEA total number of subjects
    72
    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)
    72
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 160 participants were screened, of this 72 participants were enrolled and received at least 1 dose of study drug.

    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
    No

    Arm title
    Panel 1
    Arm description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL (milligram per millilitre), fasted / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.
    Arm type
    Experimental

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - capsule, hard (G007) - 150mg
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with one Simeprevir 150 mg (milligram) capsule orally under fed condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - oral suspension (G026) - 20mg/ml
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with Simeprevir 150 mg (milligram) oral suspension (20 mg/mL (milligram per millilitre))under fasted condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - oral suspension (G026) - 20mg/ml
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with Simeprevir 150 mg (milligram) oral suspension (20 mg/mL (milligram per millilitre))under fed condition.

    Arm title
    Panel 3
    Arm description
    Participants were administered with Single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 concept capsule K, fed high-fat breakfast consisted of 56 g fat, 928 kcal / Single oral dose of 150 mg TMC435 concept capsule L, fed high-fat breakfast consisted of 56 g fat, 928 kcal
    Arm type
    Experimental

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - capsule, hard (G007) - 150mg
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with one Simeprevir 150 mg (milligram) capsule orally under fed condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - capsule, hard (G019 concept K) - 150mg
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with one Simeprevir 150 mg (milligram) capsule (concept formulation K)orally under fed condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - capsule, hard (G019 concept L) - 150mg
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with one Simeprevir 150 mg (milligram) capsule (G019 concept formulation L) orally under fed condition.

    Arm title
    Panel 2
    Arm description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL ) (milligram per millilitre)), fasted / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.
    Arm type
    Experimental

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - capsule, hard (G007) - 150mg
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with one Simeprevir 150 mg (milligram) capsule orally under fed condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - oral solution (G025) - 10mg/ml
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with Simeprevir 150 mg (milligram) oral solution (10 mg/mL (milligram per millilitre))under fed condition.

    Investigational medicinal product name
    Simeprevir
    Investigational medicinal product code
    TMC435
    Other name
    JNJ-38733214-AAA - oral solution (G025) - 10mg/ml
    Pharmaceutical forms
    Oral solution
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered with Simeprevir 150 mg (milligram) oral solution (10 mg/mL (milligram per millilitre))under fasted condition.

    Number of subjects in period 1
    Panel 1 Panel 3 Panel 2
    Started
    24
    24
    24
    Completed
    24
    24
    24

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Panel 1
    Reporting group description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL (milligram per millilitre), fasted / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.

    Reporting group title
    Panel 3
    Reporting group description
    Participants were administered with Single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 concept capsule K, fed high-fat breakfast consisted of 56 g fat, 928 kcal / Single oral dose of 150 mg TMC435 concept capsule L, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 2
    Reporting group description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL ) (milligram per millilitre)), fasted / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.

    Reporting group values
    Panel 1 Panel 3 Panel 2 Total
    Number of subjects
    24 24 24 72
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    24 24 24 72
        From 65 to 84 years
    0 0 0 0
        85 years and over
    0 0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    34.3 ( 10.94 ) 34.7 ( 9.09 ) 29.9 ( 6.95 ) -
    Title for Gender
    Units: subjects
        Female
    9 9 11 29
        Male
    15 15 13 43

    End points

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    End points reporting groups
    Reporting group title
    Panel 1
    Reporting group description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL (milligram per millilitre), fasted / Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.

    Reporting group title
    Panel 3
    Reporting group description
    Participants were administered with Single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 concept capsule K, fed high-fat breakfast consisted of 56 g fat, 928 kcal / Single oral dose of 150 mg TMC435 concept capsule L, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 2
    Reporting group description
    Participants were administered with single oral dose of 150 mg (milligrams) TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g (grams) fat, 928 kcal (kilocalories) / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL ) (milligram per millilitre)), fasted / Single oral dose of 150 mg TMC435 oral solution (10 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal.

    Subject analysis set title
    PANEL 1: 150 mg Capsule Fed (Reference)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with one Simeprevir 150 mg (milligram) capsule orally under fed condition (Reference).

    Subject analysis set title
    PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with Simeprevir 150 mg (milligram) oral suspension 20 mg/mL (milligram per millilitre) under fed condition (Test 2).

    Subject analysis set title
    PANEL 2: 150 mg Capsule Fed (Reference 1)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with simeprevir 150 mg(milligrams) capsule orally under Fed conditions (Reference 1).

    Subject analysis set title
    PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with Simeprevir 150 mg (milligram) oral suspension 20 mg/mL (milligram per millilitre) under fasted condition (Test 1).

    Subject analysis set title
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with Simeprevir Oral Solution (10 mg/mL milligram per millilitre) under Fed condition (Test).

    Subject analysis set title
    PANEL 3: 150 mg Capsule Fed (Reference)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with one Simeprevir 150 mg (milligram) capsule orally under fed condition (Reference).

    Subject analysis set title
    PANEL 3: 150 mg Capsule Concept K Fed (Test 1)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with concept K 150 mg(milligrams) capsule orally under Fed conditions (Test 1).

    Subject analysis set title
    PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with Simeprevir Oral Solution (10 mg/mL milligram per millilitre) under Fasted condition (Reference 2).

    Subject analysis set title
    PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Participants were administered with concept L 150 mg(milligrams) capsule orally under Fed conditions (Test 2).

    Primary: Maximum serum concentration (Cmax) after administration of a single dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    Maximum serum concentration (Cmax) after administration of a single dose of TMC435, Oral Suspension and Oral Solution
    End point description
    The Cmax is defined as maximum observed serum concentrations of TMC435. The value '99999' indicates that the data were not reported at specific time points.
    End point type
    Primary
    End point timeframe
    4 days
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: Nanogram per millilitre(ng/mL)
        arithmetic mean (standard deviation)
    962 ( 331 )
    9.3 ( 6.67 )
    954 ( 375 )
    99999 ( 99999 )
    1000 ( 440 )
    949 ( 330 )
    910 ( 256 )
    1250 ( 537 )
    941 ( 379 )
    Statistical analysis title
    Test vs Reference 1
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test) v PANEL 2: 150 mg Capsule Fed (Reference 1)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    103.69
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    87.89
         upper limit
    122.34
    Statistical analysis title
    Test vs Reference 2
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) v PANEL 2:Oral Solution (10 mg/mL) Fed (Test)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    80.62
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    68.33
         upper limit
    95.12
    Statistical analysis title
    Test 1 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Concept K Fed (Test 1) v PANEL 3: 150 mg Capsule Fed (Reference)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    97.37
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    86.02
         upper limit
    110.21
    Statistical analysis title
    Test 2 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Concept L Fed (Test 2) v PANEL 3: 150 mg Capsule Fed (Reference)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    97.5
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    86.14
         upper limit
    110.35

    Primary: The time taken to reach the maximum concentration (Tmax) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    The time taken to reach the maximum concentration (Tmax) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution [1]
    End point description
    The Tmax is defined as the time taken to reach the maximum concentration of TMC435 (Fed and Fasted Conditions).
    End point type
    Primary
    End point timeframe
    4 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: hours (h)
        median (full range (min-max))
    7.99 (1.98 to 24.05)
    12 (3.98 to 24.02)
    8.01 (3.97 to 12.03)
    6 (3 to 8.02)
    11.97 (4 to 24.05)
    6 (1.98 to 12.08)
    6.02 (1.98 to 12)
    4 (2 to 6.03)
    6.03 (1.98 to 12.02)
    No statistical analyses for this end point

    Primary: Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUC last) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUC last) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution
    End point description
    The AUC last is defined as Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUC last) of TMC435 (Fed and Fasted Conditions). The value '99999' indicates that the data were not reported at specific time points.
    End point type
    Primary
    End point timeframe
    4 Days
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: Nanogram*hour/millilitre(ng*h/mL)
        arithmetic mean (standard deviation)
    14503 ( 6308 )
    129 ( 123 )
    14939 ( 5517 )
    99999 ( 99999 )
    16483 ( 5163 )
    13477 ( 4332 )
    12908 ( 3933 )
    15223 ( 6971 )
    12750 ( 5069 )
    Statistical analysis title
    Test vs Reference 1
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test) v PANEL 2: 150 mg Capsule Fed (Reference 1)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    112.27
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    99.04
         upper limit
    127.26
    Statistical analysis title
    Test vs Reference 2
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test) v PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    112.24
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    99.02
         upper limit
    127.23
    Statistical analysis title
    Test 1 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Fed (Reference) v PANEL 3: 150 mg Capsule Concept K Fed (Test 1)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    96.49
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    88.45
         upper limit
    105.26
    Statistical analysis title
    Test 2 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Concept L Fed (Test 2) v PANEL 3: 150 mg Capsule Fed (Reference)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    93.79
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    85.98
         upper limit
    102.32

    Primary: Area under the plasma concentration (AUC Infinite) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    Area under the plasma concentration (AUC Infinite) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution
    End point description
    The AUC (0-infinity) is the area under the serum TMC435 concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C (last)/lambda (z), in which AUC (0-last) is area under the serum TMC435 concentration-time curve from time zero to time of the last quantifiable concentration of TMC435 (Fed and Fasted Conditions). The value '99999' indicates that the data were not reported at specific time points.
    End point type
    Primary
    End point timeframe
    4 Days
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: Nanogram/millilitre*hour(ng/mL*h)
        arithmetic mean (standard deviation)
    13831 ( 5237 )
    99999 ( 99999 )
    15377 ( 5533 )
    99999 ( 99999 )
    16408 ( 5240 )
    13588 ( 4401 )
    13007 ( 3991 )
    15321 ( 7027 )
    12852 ( 5131 )
    Statistical analysis title
    Test vs Reference 1
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test) v PANEL 2: 150 mg Capsule Fed (Reference 1)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    111.38
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    97.65
         upper limit
    127.03
    Statistical analysis title
    Test vs Reference 2
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 2:Oral Solution (10 mg/mL) Fed (Test) v PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    112.22
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    98.57
         upper limit
    127.76
    Statistical analysis title
    Test 1 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Concept K Fed (Test 1) v PANEL 3: 150 mg Capsule Fed (Reference)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    96.43
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    88.44
         upper limit
    105.14
    Statistical analysis title
    Test 2 vs Reference
    Statistical analysis description
    EudraCT database performs auto-addition of number of subjects analyzed while reporting statistical analysis of two treatment groups. The number of subjects included in analysis were '24" instead of '48'.
    Comparison groups
    PANEL 3: 150 mg Capsule Concept L Fed (Test 2) v PANEL 3: 150 mg Capsule Fed (Reference)
    Number of subjects included in analysis
    48
    Analysis specification
    Post-hoc
    Analysis type
    non-inferiority
    Method
    Parameter type
    LSmean Ratio
    Point estimate
    93.76
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    85.98
         upper limit
    102.23

    Primary: Rate constant (z) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    Rate constant (z) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution [2]
    End point description
    The z is defined as first-order rate constant associated with the terminal portion of the curve, determined by linear regression of the terminal points of the semi logarithmic drug concentration-time Curve of TMC435 (Fed and Fasted Conditions).The value '99999' indicates that the data were not reported at specific time points.
    End point type
    Primary
    End point timeframe
    4 Days
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: 1 per hour (1/h)
        arithmetic mean (standard deviation)
    0.0793 ( 0.0118 )
    99999 ( 99999 )
    0.076 ( 0.0134 )
    99999 ( 99999 )
    0.0806 ( 0.0118 )
    0.0799 ( 0.0105 )
    0.0801 ( 0.0116 )
    0.0807 ( 0.0163 )
    0.0798 ( 0.0126 )
    No statistical analyses for this end point

    Primary: Terminal elimination half-life (T1/2 term) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution

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    End point title
    Terminal elimination half-life (T1/2 term) after administration of a single Dose of TMC435, Oral Suspension and Oral Solution [3]
    End point description
    The T1/2 term is defined as the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. of TMC435 (Fed and Fasted Conditions). The value '99999' indicates that the data were not reported at specific time points.
    End point type
    Primary
    End point timeframe
    4 Days
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis were performed for this endpoint.
    End point values
    PANEL 1: 150 mg Capsule Fed (Reference) PANEL 1: Oral Suspension (20 mg/mL) Fed (Test 2) PANEL 2: 150 mg Capsule Fed (Reference 1) PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2:Oral Solution (10 mg/mL) Fed (Test) PANEL 3: 150 mg Capsule Fed (Reference) PANEL 3: 150 mg Capsule Concept K Fed (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2) PANEL 3: 150 mg Capsule Concept L Fed (Test 2)
    Number of subjects analysed
    24
    24
    24
    24
    24
    24
    24
    24
    24
    Units: hours (h)
        arithmetic mean (standard deviation)
    8.9 ( 1.5 )
    99999 ( 99999 )
    9.4 ( 1.7 )
    99999 ( 99999 )
    8.8 ( 1.1 )
    8.8 ( 1.4 )
    8.8 ( 1.4 )
    8.9 ( 1.6 )
    8.9 ( 1.5 )
    No statistical analyses for this end point

    Secondary: Overall Taste

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    End point title
    Overall Taste
    End point description
    Participants had to select appropriate choice Bad, Almost acceptable, Acceptable and Good for the overall taste.
    End point type
    Secondary
    End point timeframe
    Day 1 of Panel 1 and Panel 2
    End point values
    PANEL 1: Oral Suspension (20 mg/mL) Fasted (Test 1) PANEL 2: Oral Solution (10 mg/mL) Fasted (Reference 2)
    Number of subjects analysed
    24
    24
    Units: Participants
    arithmetic mean (standard deviation)
        Overall taste
    2.1 ( 0.65 )
    1.4 ( 0.77 )
        Visual analog scale
    0.7 ( 0.95 )
    -0.6 ( 0.83 )
        Sweetness
    1.9 ( 0.8 )
    0.5 ( 0.72 )
        Bitterness
    0.5 ( 0.83 )
    1.1 ( 1.18 )
        Flavor
    1.8 ( 0.59 )
    1.3 ( 0.92 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Screening to Follow up (5 and 7 days after last intake of TMC435)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Panel 1-150 mg Capsule Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 2-150 mg Capsule Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 1-Oral Suspension (20 mg/mL) Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 1-Oral Suspension (20 mg/mL) Fasted
    Reporting group description
    Single oral dose of 150 mg TMC435 oral suspension (20 mg/mL), fasted

    Reporting group title
    Panel 3-150 mg Capsule Concept K Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 concept capsule K, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 3-150 mg Capsule Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 Phase III capsule, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 2-Oral Solution (10 mg/mL) Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 oral solution (10 mg/mL), fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 3-150 mg Capsule Concept L Fed
    Reporting group description
    Single oral dose of 150 mg TMC435 concept capsule L, fed high-fat breakfast consisted of 56 g fat, 928 kcal

    Reporting group title
    Panel 2-Oral Solution (10 mg/mL) Fasted
    Reporting group description
    Single oral dose of 150 mg TMC435 oral solution (10 mg/mL), fasted

    Serious adverse events
    Panel 1-150 mg Capsule Fed Panel 2-150 mg Capsule Fed Panel 1-Oral Suspension (20 mg/mL) Fed Panel 1-Oral Suspension (20 mg/mL) Fasted Panel 3-150 mg Capsule Concept K Fed Panel 3-150 mg Capsule Fed Panel 2-Oral Solution (10 mg/mL) Fed Panel 3-150 mg Capsule Concept L Fed Panel 2-Oral Solution (10 mg/mL) Fasted
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 4%
    Non-serious adverse events
    Panel 1-150 mg Capsule Fed Panel 2-150 mg Capsule Fed Panel 1-Oral Suspension (20 mg/mL) Fed Panel 1-Oral Suspension (20 mg/mL) Fasted Panel 3-150 mg Capsule Concept K Fed Panel 3-150 mg Capsule Fed Panel 2-Oral Solution (10 mg/mL) Fed Panel 3-150 mg Capsule Concept L Fed Panel 2-Oral Solution (10 mg/mL) Fasted
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 24 (12.50%)
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    2 / 24 (8.33%)
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    4 / 24 (16.67%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    Cardiac disorders
    Palpitations
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Headache
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    0
    0
    0
    0
    Lethargy
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    3
    1
    0
    0
    0
    0
    0
    0
    0
    Flatulence
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Psychiatric disorders
    Abnormal Dreams
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    Sleep Disorder
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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

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