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    Clinical Trial Results:
    A Phase 1, Open-label, Single-dose Study to Assess the Mass Balance, Route of Elimination, and Metabolic Profile of [14C]-labeled MGCD516 Malate Salt in Healthy Male Subjects

    Summary
    EudraCT number
    		 2019-003898-26
    Trial protocol
    		 NL  
    Global end of trial date
    06 Feb 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Sep 2021
    First version publication date
    19 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    516-007
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Mirati Therapeutics, Inc.
    Sponsor organisation address
    3545 Cray Court, San Diego, CA, United States, 92121
    Public contact
    Michael Lane, Senior Manager, Regulatory Affairs, Mirati Therapeutics, Inc., +1 619-816-4358, lanem@mirati.com
    Scientific contact
    Curtis Chin MD PhD, Medical Director, Mirati Therapeutics, Inc., +1 619-816-4272, chinc@mirati.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
    06 Feb 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objectives of the trial were to: • Characterize the absorption, metabolism, and excretion (AME), and mass balance of a single oral dose of 120 mg MGCD516 (therapeutic dose) containing 3.7 megabecquerel (MBq) of [14C]-labeled MGCD516 in healthy male participants. • Determine the rate and routes of excretion of MGCD516 in urine and feces.
    Protection of trial subjects
    The study was conducted in accordance with the principles of the Declaration of Helsinki in place at the time of study conduct. The study was conducted in compliance with the International Council for Harmonisation (ICH) E6(R2) Guideline for Good Clinical Practice (GCP) (European Medicines Agency [EMA]/Committee for Medicinal Products for Human Use [CHMP]/ICH/135/1995), and compliant with the European Union (EU) Clinical Trial Directive (CTD): Directive 2001/20/EC.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Dec 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
    Netherlands: 6
    Worldwide total number of subjects
    6
    EEA total number of subjects
    6
    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)
    6
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 6 male participants were enrolled at a single site in the Netherlands.

    Pre-assignment
    Screening details
    		 18 participants were screened within 3 weeks prior to dosing for participation in the study. Of these, 7 participants were screening failures and 5 participants were approved but not included in the study. 6 participants were enrolled and received the study drug.

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

    Arms
    Arm title
    		 120 mg MGCD516
    Arm description
    		 Participants were administered a single oral dose of 120 mg MGCD516 containing approximately 3.7 MBq of [14C]-MGCD516 on Day 1 of the treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MGCD516
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    MGCD516 was administered as an oral capsule.

    Number of subjects in period 1
    		120 mg MGCD516
    Started
    6
    Received Treatment
    6
    Completed
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    120 mg MGCD516
    Reporting group description
    		 Participants were administered a single oral dose of 120 mg MGCD516 containing approximately 3.7 MBq of [14C]-MGCD516 on Day 1 of the treatment period.

    Reporting group values
    		 120 mg MGCD516 Total
    Number of subjects
    		 6 6
    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)
    		 6 6
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 28 ± 6 -
    Gender categorical
    Units: Subjects
        Female
    		 0 0
        Male
    		 6 6
    Race
    Units: Subjects
        White
    		 5 5
        Asian
    		 1 1
    Ethnicity
    Units: Subjects
        Not Hispanic or Latino
    		 6 6

    End points

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    End points reporting groups
    Reporting group title
    120 mg MGCD516
    Reporting group description
    		 Participants were administered a single oral dose of 120 mg MGCD516 containing approximately 3.7 MBq of [14C]-MGCD516 on Day 1 of the treatment period.

    Primary: Maximum Observed Plasma Concentration (Cmax) of MGCD516 in Plasma

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of MGCD516 in Plasma [1]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: nanograms per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    66.0 ± 15.6
    No statistical analyses for this end point

    Primary: Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Total Radioactivity in Plasma and Whole Blood [2]
    End point description
    The unit of measurement for Cmax is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    251 ± 18.0
        Total Radioactivity in Whole Blood
    186 ± 17.4
    No statistical analyses for this end point

    Primary: Time to Attain Maximum Observed Plasma Concentration (tmax) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Time to Attain Maximum Observed Plasma Concentration (tmax) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood [3]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: hours
    median (full range (min-max))
        MGCD516 in Plasma
    11.01 (8.00 to 12.20)
        Total Radioactivity in Plasma
    18.01 (8.00 to 24.00)
        Total Radioactivity in Whole Blood
    10.00 (8.00 to 12.20)
    No statistical analyses for this end point

    Primary: Terminal Phase Rate Constant (kel) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Terminal Phase Rate Constant (kel) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood [4]
    End point description
    Kel was calculated by linear regression of the terminal log-linear portion of the concentration vs time curve. Linear regression of at least 3 points was required to obtain a reliable kel.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [4] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: per hour (/h)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    0.0141 ± 4.2
        Total Radioactivity in Plasma
    0.00760 ± 2.6
        Total Radioactivity in Whole Blood
    0.0145 ± 2.6
    No statistical analyses for this end point

    Primary: Terminal Elimination Half-life (t1/2) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Terminal Elimination Half-life (t1/2) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood [5]
    End point description
    t1/2 was calculated as 0.693/kel.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [5] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: hours (h)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    49.3 ± 14.2
        Total Radioactivity in Plasma
    91.2 ± 22.6
        Total Radioactivity in Whole Blood
    47.7 ± 22.6
    No statistical analyses for this end point

    Primary: Time of Last Observed Plasma Concentration (tlast) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Time of Last Observed Plasma Concentration (tlast) of MGCD516 in Plasma and for Total Radioactivity in Plasma and Whole Blood [6]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [6] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: hours (h)
    median (full range (min-max))
        MGCD516 in Plasma
    360.00 (336.00 to 360.13)
        Total Radioactivity in Plasma
    240.00 (192.00 to 336.00)
        Total Radioactivity in Whole Blood
    96.00 (96.00 to 144.00)
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over an Interval of 0-12 Hours (AUC0-12) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over an Interval of 0-12 Hours (AUC0-12) of Total Radioactivity in Plasma and Whole Blood [7]
    End point description
    The unit of measurement for AUC0-12 is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1: Predose, and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose
    Notes
    [7] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    2015 ± 19.8
        Total Radioactivity in Whole Blood
    1529 ± 20.1
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over an Interval of 0-24 Hours (AUC0-24) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over an Interval of 0-24 Hours (AUC0-24) of Total Radioactivity in Plasma and Whole Blood [8]
    End point description
    The unit of measurement for AUC0-24 is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 2: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 postdose on Day 1 and 24 hours postdose
    Notes
    [8] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    4933 ± 18.3
        Total Radioactivity in Whole Blood
    3629 ± 16.6
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve up to Time t (AUC0-t) for MGCD516 in Plasma

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    End point title
    		 Area Under the Plasma Concentration-time Curve up to Time t (AUC0-t) for MGCD516 in Plasma [9]
    End point description
    Time t was defined as the last point with concentrations above the lower limit of quantitation.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [9] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: nanogram hours per milliliter (h.ng/mL)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    3253 ± 13.9
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve up to Time t (AUC0-t) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Area Under the Plasma Concentration-time Curve up to Time t (AUC0-t) of Total Radioactivity in Plasma and Whole Blood [10]
    End point description
    Time t was defined as the last point with concentrations above the lower limit of quantitation. The unit of measurement for AUC0-t is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [10] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    22053 ± 18.5
        Total Radioactivity in Whole Blood
    11211 ± 12.5
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) of MGCD516 in Plasma

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) of MGCD516 in Plasma [11]
    End point description
    AUC0-inf was calculated as AUC0-inf = AUC0-t + Clast/kel, where Clast is the last measurable plasma concentration and kel is the terminal elimination rate constant.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [11] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: nanogram hours per milliliter (h.ng/mL)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    3260 ± 14.0
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Area Under the Plasma Concentration-time Curve from Time 0 to Infinity (AUC0-inf) of Total Radioactivity in Plasma and Whole Blood [12]
    End point description
    AUC0-inf was calculated as AUC0-inf = AUC0-t + Clast/kel, where Clast is the last measurable plasma concentration and kel is the terminal elimination rate constant. The unit of measurement for AUC0-inf is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [12] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    25113 ± 18.6
        Total Radioactivity in Whole Blood
    14863 ± 12.1
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over an Interval of 0-144 Hours (AUC0-144) of MGCD516 in Plasma

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over an Interval of 0-144 Hours (AUC0-144) of MGCD516 in Plasma [13]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 7: Predose and 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and 24, 48, 72, 96 and 144 hours postdose
    Notes
    [13] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: nanogram hours per milliliter (h.ng/mL)
    geometric mean (geometric coefficient of variation)
        MGCD516 in Plasma
    3110 ± 12.9
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over an Interval of 0-144 Hours (AUC0-144) of Total Radioactivity in Plasma and Whole Blood

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over an Interval of 0-144 Hours (AUC0-144) of Total Radioactivity in Plasma and Whole Blood [14]
    End point description
    The unit of measurement for AUC0-144 is equivalent nanogram hours per milliliter (h.ngEq/mL).
    End point type
    Primary
    End point timeframe
    Day 1 to Day 7: Predose and 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and 24, 48, 72, 96 and 144 hours postdose
    Notes
    [14] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: h.ngEq/mL
    geometric mean (geometric coefficient of variation)
        Total Radioactivity in Plasma
    18282 ± 13.3
        Total Radioactivity in Whole Blood
    12325 ± 10.4
    No statistical analyses for this end point

    Primary: Apparent Oral Clearance (CL/F) of MGCD516 in Plasma

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    End point title
    		 Apparent Oral Clearance (CL/F) of MGCD516 in Plasma [15]
    End point description
    CL/F was calculated as dose/AUC0-inf.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [15] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: liters per hour (L/h)
        geometric mean (geometric coefficient of variation)
    36.8 ± 14.0
    No statistical analyses for this end point

    Primary: Apparent Volume of Distribution at Terminal Phase (Vz/F) of MGCD516 in Plasma

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    End point title
    		 Apparent Volume of Distribution at Terminal Phase (Vz/F) of MGCD516 in Plasma [16]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72, 96, 144, 192, 240, 288, 312, 336, and 360 hours postdose
    Notes
    [16] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: liters (L)
        geometric mean (geometric coefficient of variation)
    2619 ± 10.9
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-12 hours (AUC0-12) Whole Blood to Plasma Ratio for Total Radioactivity

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-12 hours (AUC0-12) Whole Blood to Plasma Ratio for Total Radioactivity [17]
    End point description
    Calculated as AUC0-12,blood / AUC0-12,plasma.
    End point type
    Primary
    End point timeframe
    Day 1: Predose, and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose
    Notes
    [17] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: ratio
        geometric mean (geometric coefficient of variation)
    0.76 ± 3.4
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-24 hours (AUC0-24) Whole Blood to Plasma Ratio for Total Radioactivity

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-24 hours (AUC0-24) Whole Blood to Plasma Ratio for Total Radioactivity [18]
    End point description
    Calculated as AUC0-24,blood / AUC0-24,plasma.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 2: Predose and 1, 2, 3, 4, 6, 8, 10, 12 postdose on Day 1 and 24 hours postdose
    Notes
    [18] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: ratio
        geometric mean (geometric coefficient of variation)
    0.74 ± 3.5
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-96 hours (AUC0-96) Whole Blood to Plasma Ratio for Total Radioactivity

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-96 hours (AUC0-96) Whole Blood to Plasma Ratio for Total Radioactivity [19]
    End point description
    Calculated as AUC0-96,blood / AUC0-96,plasma
    End point type
    Primary
    End point timeframe
    Day 1: Predose and 1, 2, 3, 4, 6, 8, 10 and 12 hours postdose on Day 1 and 24, 48, 72 and 96 hours postdose
    Notes
    [19] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: ratio
        geometric mean (geometric coefficient of variation)
    0.71 ± 3.9
    No statistical analyses for this end point

    Primary: Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-144 hours (AUC0-144) Whole Blood to Plasma Ratio for Total Radioactivity

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    End point title
    		 Area Under the Plasma Concentration-time Curve Over a Dosing Interval of 0-144 hours (AUC0-144) Whole Blood to Plasma Ratio for Total Radioactivity [20]
    End point description
    Calculated as AUC0-144,blood / AUC0-144,plasma
    End point type
    Primary
    End point timeframe
    Day 1 to Day 7: Predose and 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and 24, 48, 72, 96 and 144 hours postdose
    Notes
    [20] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: ratio
        geometric mean (geometric coefficient of variation)
    0.67 ± 5.1
    No statistical analyses for this end point

    Primary: Cumulative Amount of MGCD516 Excreted Unchanged in Urine up to the Last Quantifiable Concentration (Aeurine)

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    End point title
    		 Cumulative Amount of MGCD516 Excreted Unchanged in Urine up to the Last Quantifiable Concentration (Aeurine) [21]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose on Day 1 to 360 hours postdose
    Notes
    [21] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: micrograms (μg)
        arithmetic mean (standard deviation)
    62.7 ± 30.0
    No statistical analyses for this end point

    Primary: Cumulative Percentage of Total MGCD516 Excreted Unchanged in Urine (feurine) up to the Last Quantifiable Concentration

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    End point title
    		 Cumulative Percentage of Total MGCD516 Excreted Unchanged in Urine (feurine) up to the Last Quantifiable Concentration [22]
    End point description
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose on Day 1 to 360 hours postdose
    Notes
    [22] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: percentage of MGCD516
        arithmetic mean (standard deviation)
    0.05 ± 0.03
    No statistical analyses for this end point

    Primary: Renal Clearance of MGCD516 (CLR)

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    End point title
    		 Renal Clearance of MGCD516 (CLR) [23]
    End point description
    Calculated as cumulative Aeurine / AUC0-t.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose on Day 1 to 360 hours postdose
    Notes
    [23] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: liters per hour (L/h)
        arithmetic mean (standard deviation)
    0.0190 ± 0.00726
    No statistical analyses for this end point

    Primary: Cumulative Amount of Total Radioactivity Excreted Unchanged in Urine (Aeurine), Feces (Aefeces) and Total Urine and Feces (Aetotal) up to the Last Quantifiable Concentration

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    End point title
    		 Cumulative Amount of Total Radioactivity Excreted Unchanged in Urine (Aeurine), Feces (Aefeces) and Total Urine and Feces (Aetotal) up to the Last Quantifiable Concentration [24]
    End point description
    Aetotal was calculated as cumulative Aeurine + cumulative Aefeces
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose on Day 1 to 360 hours postdose
    Notes
    [24] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: equivalent milligrams (mgEq)
    arithmetic mean (standard deviation)
        Aeurine 0-144 hours
    3.99 ± 0.973
        Aefeces 0-144 hours
    154 ± 11.7
        Aetotal 0-144 hours
    158 ± 12.1
        Aeurine 0-360 hours
    4.52 ± 1.09
        Aefeces 0-360 hours
    168 ± 13.1
        Aetotal 0-360 hours
    172 ± 13.8
    No statistical analyses for this end point

    Primary: Cumulative Percentage of Total Radioactivity Excreted Unchanged in Urine (feurine), Feces (fefeces) and Total Urine and Feces (fetotal) up to the Last Quantifiable Concentration

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    End point title
    		 Cumulative Percentage of Total Radioactivity Excreted Unchanged in Urine (feurine), Feces (fefeces) and Total Urine and Feces (fetotal) up to the Last Quantifiable Concentration [25]
    End point description
    Fetotal was calculated as cumulative feurine + cumulative fefeces / dose
    End point type
    Primary
    End point timeframe
    Day 1 to Day 16: Predose on Day 1 to 360 hours postdose
    Notes
    [25] - 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 analyses were planned for this endpoint.
    End point values
    		 120 mg MGCD516
    Number of subjects analysed
    6
    Units: percentage of total radioactivity
    arithmetic mean (standard deviation)
        Feurine 0-144 hours
    2.6 ± 0.6
        Fefeces 0-144 hours
    98.9 ± 7.8
        Fetotal 0-144 hours
    101.5 ± 8.3
        Feurine 0-360 hours
    2.9 ± 0.7
        Fefeces 0-360 hours
    108.1 ± 8.7
        Fetotal 0-360 hours
    111.0 ± 9.3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to end of follow-up (maximum time to follow-up was 20 days)
    Adverse event reporting additional description
    Mortality, serious adverse events and non-serious adverse events are reported for all participants who enrolled in the study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    120 mg MGCD516
    Reporting group description
    		 Participants were administered a single oral dose of 120 mg MGCD516 containing approximately 3.7 MBq of [14C]-MGCD516 on Day 1 of the treatment period.

    Serious adverse events
    		 120 mg MGCD516
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 120 mg MGCD516
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 6 (33.33%)
         occurrences all number
    2
    Paraesthesia
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Presyncope
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    General disorders and administration site conditions
    Influenza Like Illness
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Injection Site Haematoma
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Injection Site Irritation
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Gastrointestinal disorders
    Gastrointestinal Sounds Abnormal
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Abdominal Discomfort
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Oropharyngeal Pain
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Skin Irritation
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    1 / 6 (16.67%)
         occurrences all number
    1

    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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