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    Clinical Trial Results:
    SMT C11003 - A Phase 1b placebo-controlled, multi-centre, randomized, double-blind 3-period dose escalation study to evaluate the pharmacokinetics (PK) and safety of SMT C1100 in paediatric patients with Duchenne Muscular Dystrophy (DMD) who follow a balanced diet.

    Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
    Summary
    EudraCT number
    		 2014-003100-78
    Trial protocol
    		 GB  
    Global end of trial date
    06 Jul 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Jun 2016
    First version publication date
    17 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    SMT C11003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Summit (Oxford) Limited
    Sponsor organisation address
    85b Park Drive, Milton Park, Abingdon, Oxfordshire, United Kingdom, OX14 4RY
    Public contact
    Clinical Trial Information, Summit (Oxford) Limited, 44 1235 443939, dmd@summitplc.com
    Scientific contact
    Clinical Trial Information, Summit (Oxford) Limited, 44 1235 443939, dmd@summitplc.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
    10 Dec 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD who follow a balanced diet
    Protection of trial subjects
    Prior to commencement of the study, each patient and their parent/legal guardian were provided with a study-specific assent form and informed consent form giving details of the investigational medicinal product, procedures and potential risks involved. For a patient not qualified or incapable of giving legal consent, written consent was obtained from the legally acceptable representative (legal guardian). Informed consent was obtained from the patient’s legally acceptable representative (legal guardian) plus the caregiver’s assent (if caregiver was other than the legal guardian). The patient’s assent was also obtained, consistent with local regulations. Patients and their parent/legal guardian were instructed that they were free to obtain further information from the Investigator and that they were free to withdraw their consent and to discontinue their participation in the study at any time. At the same time, the parent/legal guardian was informed about the existence of an indemnification procedure between the Sponsor and the Investigator and their obligations in this respect.
    Background therapy
    		 During the study, systemic corticosteroids (stable dose for 6 months prior to start of study), angiotensin converting enzyme inhibitors, angiotensin-receptor blockers, beta blockers, bisphosphonates and vitamin D and calcium supplements were permitted.
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    04 Feb 2015
    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: 12
    Worldwide total number of subjects
    12
    EEA total number of subjects
    12
    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)
    10
    Adolescents (12-17 years)
    2
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The first informed consent was given on 04 February 2015, and the date of the final post study observation was 06 July 2015

    Pre-assignment
    Screening details
    		 Patients were screened no more than 4 weeks prior to their first dose and 3 weeks prior to the dietary run-in period.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    Selected members of the Clinical Research Organisation (CRO) Pharmacokinetic (PK) group were unblinded in order to assess PK data from the preceding treatment period to determine whether stopping criteria for SMT C1100 had been met at each dose escalation meeting. The CRO, Sponsor, and Chief Investigator may also have been unblinded to the treatment assignment if a patient met stopping criteria.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment sequence 1
    Arm description
    		 Subjects who received SMT C1100 1250mg twice daily in treatment period 1, placebo twice daily in treatment period 2, and SMT C1100 2500mg twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SMT C1100
    Investigational medicinal product code
    Other name
    ezutromid
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of an aqueous microfluidised suspension of SMT C1100 via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving 1250 mg SMT C1100 1 bottle contained SMT C1100 and the other contained placebo; and when receiving 2500 mg SMT C1100 both bottles contained SMT C1100.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of placebo via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving placebo both the 2 bottles contained placebo.

    Arm title
    		 Treatment sequence 2
    Arm description
    		 Subjects who received SMT C1100 1250mg twice daily in treatment period 1, SMT C1100 2500mg twice daily in treatment period 2, and placebo twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SMT C1100
    Investigational medicinal product code
    Other name
    ezutromid
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of an aqueous microfluidised suspension of SMT C1100 via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving 1250 mg SMT C1100 1 bottle contained SMT C1100 and the other contained placebo; and when receiving 2500 mg SMT C1100 both bottles contained SMT C1100.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of placebo via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving placebo both the 2 bottles contained placebo.

    Arm title
    		 Treatment sequence 3
    Arm description
    		 Subjects who received placebo twice daily in treatment period 1, SMT C1100 1250mg twice daily in treatment period 2, and SMT C1100 2500mg twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    SMT C1100
    Investigational medicinal product code
    Other name
    ezutromid
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of an aqueous microfluidised suspension of SMT C1100 via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving 1250 mg SMT C1100 1 bottle contained SMT C1100 and the other contained placebo; and when receiving 2500 mg SMT C1100 both bottles contained SMT C1100.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    On each dosing occasion, patients swallowed 12.4 mL (2 x 6.2 mL doses) of placebo via a dosing syringe, immediately after consuming a healthy balanced meal. Patients were then given 100 mL of milk to swallow immediately following dosing. Two bottles were used for each dosing, with 6.2 mL drawn from each bottle for each dose. Therefore, when receiving placebo both the 2 bottles contained placebo.

    Number of subjects in period 1
    		Treatment sequence 1 Treatment sequence 2 Treatment sequence 3
    Started
    4
    4
    4
    Treatment period 1
    4
    4
    4
    Treatment period 2
    4
    4
    4
    Treatment period 3
    4
    4
    4
    Completed study
    4
    4
    4
    Completed
    4
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 12 12
    Age categorical
    Units: Subjects
        5-7 years
    		 4 4
        8-11 years
    		 6 6
        12-13 years
    		 2 2
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 9.19 (6.6 to 13) -
    Gender categorical
    Units: Subjects
        Female
    		 0 0
        Male
    		 12 12
    Race
    Units: Subjects
        Asian
    		 1 1
        White
    		 11 11
    Age at DMD diagnosis
    Patient age at diagnosis of Duchenne muscular dystrophy
    Units: years
        arithmetic mean (full range (min-max))
    		 4.3 (1.1 to 7.7) -
    Time since DMD diagnosis
    Time since diagnosis of Duchenne muscular dystrophy
    Units: years
        arithmetic mean (full range (min-max))
    		 4.53 (1.3 to 11.9) -
    Weight
    Patient weight
    Units: kg
        arithmetic mean (full range (min-max))
    		 31.18 (20.5 to 49) -
    BMI
    Body Mass Index
    Units: kg/square metre
        arithmetic mean (full range (min-max))
    		 19.35 (14.9 to 26.1) -
    Historical NSAA score
    Historical North Star Ambulatory Assessment score
    Units: Score
        arithmetic mean (full range (min-max))
    		 23.5 (10 to 33) -

    End points

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    End points reporting groups
    Reporting group title
    Treatment sequence 1
    Reporting group description
    		 Subjects who received SMT C1100 1250mg twice daily in treatment period 1, placebo twice daily in treatment period 2, and SMT C1100 2500mg twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.

    Reporting group title
    Treatment sequence 2
    Reporting group description
    		 Subjects who received SMT C1100 1250mg twice daily in treatment period 1, SMT C1100 2500mg twice daily in treatment period 2, and placebo twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.

    Reporting group title
    Treatment sequence 3
    Reporting group description
    		 Subjects who received placebo twice daily in treatment period 1, SMT C1100 1250mg twice daily in treatment period 2, and SMT C1100 2500mg twice daily in treatment period 3. Each patient received a single dose on Day 1, followed by twice-daily dosing on Days 2 to 14 in each treatment period.

    Subject analysis set title
    SMT C1100 1250mg Day 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a single dose of SMT C1100 at 1250mg on Day 1

    Subject analysis set title
    SMT C1100 1250mg Day 14
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 1250mg twice-daily from Day 2 - Day 14

    Subject analysis set title
    SMT C1100 1250mg Day 14 - AM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 1250mg twice-daily from Day 2 - Day 14; data from samples post AM dose on Day 14

    Subject analysis set title
    SMT C1100 1250mg Day 14 – PM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 1250mg twice-daily from Day 2 - Day 14; data from samples post PM dose on Day 14

    Subject analysis set title
    SMT C1100 2500mg Day 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a single dose of SMT C1100 at 2500mg on Day 1

    Subject analysis set title
    SMT C1100 2500mg Day 14
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 2500mg twice-daily from Day 2 - Day 14

    Subject analysis set title
    SMT C1100 2500mg Day 14 - AM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 2500mg twice-daily from Day 2 - Day 14; data from samples post AM dose on Day 14

    Subject analysis set title
    SMT C1100 2500mg Day 14 - PM
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Patients who received a dose of SMT C1100 at 2500mg twice-daily from Day 2 - Day 14; data from samples post PM dose on Day 14

    Primary: AUC 0-infinity (Day 1) - SMT C1100

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    End point title
    		 AUC 0-infinity (Day 1) - SMT C1100 [1]
    End point description
    Area under the plasma concentration-time curve from zero to infinity
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    10
    9
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        SMT C1100
    359 ± 104
    474 ± 107
    No statistical analyses for this end point

    Primary: AUC 0-infinity (Day 1) - Dihydrodiol I

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    End point title
    		 AUC 0-infinity (Day 1) - Dihydrodiol I [2]
    End point description
    Area under the plasma concentration-time curve from zero to infinity
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    12
    11
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol I
    5360 ± 42
    6470 ± 47.2
    No statistical analyses for this end point

    Primary: AUC 0-infinity (Day 1) - Dihydrodiol III

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    End point title
    		 AUC 0-infinity (Day 1) - Dihydrodiol III [3]
    End point description
    Area under the plasma concentration-time curve from zero to infinity
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    10
    11
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol III
    10700 ± 60.6
    12700 ± 61.3
    No statistical analyses for this end point

    Primary: AUC 0-tlast (Day 1) - SMT C1100

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    End point title
    		 AUC 0-tlast (Day 1) - SMT C1100 [4]
    End point description
    Area under the plasma concentration-time curve from time zero to time t, where t is the last time point with a measurable concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    12
    12
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        SMT C1100
    290 ± 95.8
    436 ± 97
    No statistical analyses for this end point

    Primary: AUC 0-tlast (Day 1) - Dihydrodiol I

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    End point title
    		 AUC 0-tlast (Day 1) - Dihydrodiol I [5]
    End point description
    Area under the plasma concentration-time curve from time zero to time t, where t is the last time point with a measurable concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    12
    12
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol I
    5090 ± 38.6
    6490 ± 46.5
    No statistical analyses for this end point

    Primary: AUC 0-tlast (Day 1) - Dihydrodiol III

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    End point title
    		 AUC 0-tlast (Day 1) - Dihydrodiol III [6]
    End point description
    Area under the plasma concentration-time curve from time zero to time t, where t is the last time point with a measurable concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 2500mg Day 1
    Number of subjects analysed
    12
    12
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol III
    10700 ± 58.7
    12500 ± 58.3
    No statistical analyses for this end point

    Primary: AUC 0-tau (Day 14) - SMT C1100

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    End point title
    		 AUC 0-tau (Day 14) - SMT C1100 [7]
    End point description
    Area under the plasma concentration-time curve over a dosing interval (tau). The dosing interval (tau) approximated 12 hours. Due to the unequal dosing interval between AM and PM doses, AUC 0-tau was calculated as the total AUC over the sampling period of AM and PM divided by 2
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 14 SMT C1100 2500mg Day 14
    Number of subjects analysed
    12
    11
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        SMT C1100
    273 ± 100
    350 ± 132
    No statistical analyses for this end point

    Primary: AUC 0-tau (Day 14) - Dihydrodiol I

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    End point title
    		 AUC 0-tau (Day 14) - Dihydrodiol I [8]
    End point description
    Area under the plasma concentration-time curve over a dosing interval (tau). The dosing interval (tau) approximated 12 hours. Due to the unequal dosing interval between AM and PM doses, AUC 0-tau was calculated as the total AUC over the sampling period of AM and PM divided by 2
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 14 SMT C1100 2500mg Day 14
    Number of subjects analysed
    12
    11
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol I
    4870 ± 37.7
    6140 ± 44
    No statistical analyses for this end point

    Primary: AUC 0-tau (Day 14) - Dihydrodiol III

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    End point title
    		 AUC 0-tau (Day 14) - Dihydrodiol III [9]
    End point description
    Area under the plasma concentration-time curve over a dosing interval (tau). The dosing interval (tau) approximated 12 hours. Due to the unequal dosing interval between AM and PM doses, AUC 0-tau was calculated as the total AUC over the sampling period of AM and PM divided by 2
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 14 SMT C1100 2500mg Day 14
    Number of subjects analysed
    12
    11
    Units: ng.h/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol III
    11100 ± 43.4
    13600 ± 58.6
    No statistical analyses for this end point

    Primary: Cmax - SMT C1100

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    End point title
    		 Cmax - SMT C1100 [10]
    End point description
    Maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        SMT C1100
    49 ± 79.8
    38.7 ± 104
    43.1 ± 94
    65.6 ± 74.3
    44.9 ± 108
    61.2 ± 119
    No statistical analyses for this end point

    Primary: Cmax - Dihydrodiol I

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    End point title
    		 Cmax - Dihydrodiol I [11]
    End point description
    Maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol I
    692 ± 22.5
    631 ± 30.3
    728 ± 39.1
    840 ± 25.1
    738 ± 29.1
    894 ± 35.7
    No statistical analyses for this end point

    Primary: Cmax -Dihydrodiol III

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    End point title
    		 Cmax -Dihydrodiol III [12]
    End point description
    Maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Dihydrodiol III
    1330 ± 37.5
    1370 ± 36.5
    1550 ± 43.2
    1550 ± 33
    1520 ± 37.2
    1840 ± 50.1
    No statistical analyses for this end point

    Primary: tmax - SMT C1100

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    End point title
    		 tmax - SMT C1100 [13]
    End point description
    Time of maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: hours
    median (full range (min-max))
        SMT C1100
    2.5 (0.98 to 4.1)
    4 (2.47 to 6.02)
    1.77 (0.5 to 12)
    2.5 (1 to 6)
    4 (2.47 to 10)
    2.6 (0.5 to 6.05)
    No statistical analyses for this end point

    Primary: tmax - Dihydrodiol I

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    End point title
    		 tmax - Dihydrodiol I [14]
    End point description
    Time of maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: hours
    median (full range (min-max))
        Dihydrodiol I
    2.53 (1 to 4.1)
    3.33 (1.02 to 6.02)
    3.27 (1 to 12)
    2.56 (1 to 6)
    4 (2.47 to 6.02)
    4 (1 to 6.05)
    No statistical analyses for this end point

    Primary: tmax - Dihydrodiol III

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    End point title
    		 tmax - Dihydrodiol III [15]
    End point description
    Time of maximum observed plasma concentration
    End point type
    Primary
    End point timeframe
    PK blood samples taken after dosing on Day 1 or Day 14
    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: The primary objective of this study was to determine the single and multiple oral dose PK of SMT C1100 and its metabolites in patients with DMD. Descriptive statistics for the PK data are reported here.
    End point values
    		 SMT C1100 1250mg Day 1 SMT C1100 1250mg Day 14 - AM SMT C1100 1250mg Day 14 – PM SMT C1100 2500mg Day 1 SMT C1100 2500mg Day 14 - AM SMT C1100 2500mg Day 14 - PM
    Number of subjects analysed
    12
    12
    12
    12
    11
    11
    Units: hours
    median (full range (min-max))
        Dihydrodiol III
    4 (2.48 to 6.05)
    4.03 (2.5 to 6.02)
    5 (2.5 to 12)
    3.99 (2.5 to 6)
    4.05 (0 to 9.57)
    4 (0.5 to 9)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The condition of each patient was monitored throughout the study. In addition, when resident at the study sites any signs or symptoms were observed and elicited at least once a day by open questioning.
    Adverse event reporting additional description
    Treatment-Emergent Adverse Events (all causalities) are presented in this record. Any adverse events and remedial actions required were recorded. The nature, time of onset, duration and severity were documented, together with an Investigator’s opinion of the relationship to drug administration.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    SMT C1100 1250mg
    Reporting group description
    		 Patients who received SMT C1100 at a dose of 1250mg

    Reporting group title
    SMT C1100 2500mg
    Reporting group description
    		 Patients who received SMT C1100 at a dose of 2500mg

    Reporting group title
    SMT C1100 Overall
    Reporting group description
    		 Patients who received SMT C1100

    Reporting group title
    Placebo
    Reporting group description
    		 Patients who received placebo

    Serious adverse events
    		 SMT C1100 1250mg SMT C1100 2500mg SMT C1100 Overall Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 SMT C1100 1250mg SMT C1100 2500mg SMT C1100 Overall Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 12 (100.00%)
    12 / 12 (100.00%)
    12 / 12 (100.00%)
    12 / 12 (100.00%)
    Investigations
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    1
    Injury, poisoning and procedural complications
    Injury
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Upper limb fracture
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    2
    2
    Lethargy
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Post-traumatic headache
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Sinus headache
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Asthenia
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Faeces pale
         subjects affected / exposed
    12 / 12 (100.00%)
    11 / 12 (91.67%)
    12 / 12 (100.00%)
    9 / 12 (75.00%)
         occurrences all number
    12
    12
    24
    9
    Diarrhoea
         subjects affected / exposed
    3 / 12 (25.00%)
    3 / 12 (25.00%)
    5 / 12 (41.67%)
    2 / 12 (16.67%)
         occurrences all number
    3
    3
    6
    2
    Abdominal pain upper
         subjects affected / exposed
    3 / 12 (25.00%)
    1 / 12 (8.33%)
    3 / 12 (25.00%)
    3 / 12 (25.00%)
         occurrences all number
    5
    2
    7
    5
    Nausea
         subjects affected / exposed
    2 / 12 (16.67%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    2
    2
    Vomiting
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    1
    Haematochezia
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Constipation
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Toothache
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    1
    0
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    3
    0
    Cough
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Miliaria
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 12 (8.33%)
    3 / 12 (25.00%)
    3 / 12 (25.00%)
    2 / 12 (16.67%)
         occurrences all number
    2
    3
    5
    2
    Arthralgia
         subjects affected / exposed
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 12 (33.33%)
    2 / 12 (16.67%)
    5 / 12 (41.67%)
    1 / 12 (8.33%)
         occurrences all number
    4
    2
    6
    1
    Nail bed infection
         subjects affected / exposed
    1 / 12 (8.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 12 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    1
    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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