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    Clinical Trial Results:
    A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of MT10109L (NivobotulinumtoxinA) for the Treatment of Glabellar Lines With or Without Concurrent Treatment of Lateral Canthal Lines

    Summary
    EudraCT number
    2014-005301-21
    Trial protocol
    GB   DE  
    Global end of trial date
    22 Jan 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    15 Feb 2024
    First version publication date
    15 Feb 2024
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    MT10109L-005
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03721016
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    IND Number: 121473
    Sponsors
    Sponsor organisation name
    Medytox Inc
    Sponsor organisation address
    78, Gangni 1-gil, Ochang-eup, Cheongwon-gu,, Cheongju-si, Korea, Republic of, 28126
    Public contact
    Young Ryu, Medytox Inc, +82 2-69015424,
    Scientific contact
    Gyungjin Heo, Medytox Inc, +82 2-6901-5839, gjheo@medytox.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 Sep 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Mar 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Jan 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy between 20 U MT10109L and placebo for the treatment of GL (with or without concurrent 24 U treatment of LCL) in participants with moderate to severe GL and LCL. The total global enrollment (as presented in the "Population of Trial Subjects" below was 415, which included the Intent-To-Treat population. However, all primary and secondary efficacy analyses for EU regulatory endpoints reported here are using the mITT population that included a total of 356 participants (USA -240; Germany - 47, United-Kingdom - 20 and Canada - 49).
    Protection of trial subjects
    The study protocol, all study protocol amendments, written study participant information, informed consent form (ICF), Investigator’s Brochure (IB) and any other relevant documents were reviewed and approved by an independent ethics committee (IEC) or institutional review board (IRB) at each study center. The study was conducted in accordance with the protocol, the ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines, applicable International Council for Harmonisation (ICH)/Good Clinical Practice (GCP) and other Guidelines, and applicable laws and regulations. An ICF approved by each study center’s IEC/IRB was signed by the participant or their legally authorized representative and the authorized person obtaining the ICF before the participant was entered in the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    26 Oct 2018
    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: 23
    Country: Number of subjects enrolled
    Germany: 64
    Country: Number of subjects enrolled
    United States: 271
    Country: Number of subjects enrolled
    Canada: 57
    Worldwide total number of subjects
    415
    EEA total number of subjects
    64
    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)
    394
    From 65 to 84 years
    20
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were screened and recruited at sites in US, UK, Germany and Canada. The data described here is for the ITT population. The ITT population consisted of all randomized participants.

    Pre-assignment
    Screening details
    505 patients were screened and 415 met the incusion/exclusion criteria and were randomized.

    Period 1
    Period 1 title
    First treatment
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    Randomization and double blinding were used to minimize bias arising from the assignment of participants to treatment groups and the expectations of participants, investigators and individuals collecting data.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Placebo was injected into the Glabellar Lines (GL) and latheral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the placebo in GL & LCL areas as defined in the protocol.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate, Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0U per 0.1mL/injection Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)

    Arm title
    MT10109L 20U in GL + Placebo in LCL
    Arm description
    MT10109L 20U was injected into the Glabellar Lines (GL) and Placebo into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the MT10109L in GL & Placebo in LCL areas as defined in the protocol.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration - MT10109L in 5 GL sites; 0.1 mL/injection.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0 U/0.1 mL/injection Administration - Placebo in 6 LCL sites; 0.1 mL/injection.

    Arm title
    MT10109L 20U GL + MT10109L 24 U LCL
    Arm description
    MT10109L 20U was injected into the Glabellar Lines (GL) and MT10109L 24U injected into Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving MT10109L in GL & LCL areas as defined in the protocol.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration details - 11 injection sites (MT10109L in 5 GL sites + MT10109L in 6 LCL sites)

    Number of subjects in period 1
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Started
    82
    173
    160
    Completed
    69
    148
    141
    Not completed
    13
    25
    19
         Consent withdrawn by subject
    7
    10
    8
         Physician decision
    -
    1
    1
         site terminated by Sponsor
    3
    7
    6
         Adverse event, non-fatal
    -
    1
    1
         other
    1
    -
    -
         Lost to follow-up
    2
    6
    3
    Period 2
    Period 2 title
    Retreatment 1
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    Randomization and double-blinding were used to minimize bias arising from the assignment of participants to treatment group and the expectations of participants, investigators and individuals collecting data.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Retreatment 1 for Placebo arm
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0U per 0.1mL/injection Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)

    Arm title
    MT10109L 20U in GL + Placebo in LCL retreatment 1
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration - MT10109L in 5 GL sites; 0.1 mL/injection.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0 U/0.1 mL/injection Administration - Placebo in 6 LCL sites; 0.1 mL/injection.

    Arm title
    MT10109L 20U GL + MT10109L 24 U LCL retreatment 1
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration details - 11 injection sites (MT10109L in 5 GL sites + MT10109L in 6 LCL sites)

    Number of subjects in period 2 [1]
    Retreatment 1 for Placebo arm MT10109L 20U in GL + Placebo in LCL retreatment 1 MT10109L 20U GL + MT10109L 24 U LCL retreatment 1
    Started
    64
    145
    137
    Completed
    62
    139
    130
    Not completed
    2
    6
    7
         Consent withdrawn by subject
    -
    6
    5
         Lost to follow-up
    2
    -
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only participants from period 1 (first treatment), who met the protocol-defined retreatment criteria, were eligible to enter period 2 (Retreatment 1)
    Period 3
    Period 3 title
    Retreatment 2
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    Randomization and double blinding weere used to minimize bias arising from the assignment of participants to treatment groups and the expectations of participants, investigators and individuals collecting data.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo retreatment 2
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0U per 0.1mL/injection Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)

    Arm title
    MT10109L 20U in GL + Placebo in LCL retreatment 2
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration - MT10109L in 5 GL sites; 0.1 mL/injection.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - Placebo 0 U/0.1 mL/injection Administration - Placebo in 6 LCL sites; 0.1 mL/injection.

    Arm title
    MT10109L 20U GL + MT10109L 24 U LCL retreatment2
    Arm description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Arm type
    Experimental

    Investigational medicinal product name
    MT10109L
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection, Sterile concentrate
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Dosage - MT10109L 4 U/0.1 mL/injection; Administration details - 11 injection sites (MT10109L in 5 GL sites + MT10109L in 6 LCL sites)

    Number of subjects in period 3 [2]
    Placebo retreatment 2 MT10109L 20U in GL + Placebo in LCL retreatment 2 MT10109L 20U GL + MT10109L 24 U LCL retreatment2
    Started
    47
    95
    91
    Completed
    46
    94
    90
    Not completed
    1
    1
    1
         Consent withdrawn by subject
    1
    -
    -
         Physician decision
    -
    -
    1
         Protocol deviation
    -
    1
    -
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only participants from period 2 (Retreatment1), who met the protocol-defined retreatment criteria, were eligible to enter period 3 (Retreatment 2)

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo was injected into the Glabellar Lines (GL) and latheral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the placebo in GL & LCL areas as defined in the protocol.

    Reporting group title
    MT10109L 20U in GL + Placebo in LCL
    Reporting group description
    MT10109L 20U was injected into the Glabellar Lines (GL) and Placebo into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the MT10109L in GL & Placebo in LCL areas as defined in the protocol.

    Reporting group title
    MT10109L 20U GL + MT10109L 24 U LCL
    Reporting group description
    MT10109L 20U was injected into the Glabellar Lines (GL) and MT10109L 24U injected into Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving MT10109L in GL & LCL areas as defined in the protocol.

    Reporting group values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL Total
    Number of subjects
    82 173 160 415
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0
        Adults (18-64 years)
    78 160 156 394
        From 65-84 years
    4 12 4 20
        85 years and over
    0 1 0 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    47.6 ± 10.91 47.5 ± 11.49 46.2 ± 11.15 -
    Gender categorical
    Units: Subjects
        Female
    72 148 143 363
        Male
    10 25 17 52
    Subject analysis sets

    Subject analysis set title
    Demographic and other Baseline Characteristics - ITT
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    82 participants in the placebo group 173 participants in the MT10109L 20 U group 160 participants in the MT10109L 44 U group

    Subject analysis set title
    Demographic and other Baseline Characteristics -mITT
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    67 participants in the placebo group 155 participants in the MT10109L 20U group 134 participants in the MTL10109L 44U group

    Subject analysis sets values
    Demographic and other Baseline Characteristics - ITT Demographic and other Baseline Characteristics -mITT
    Number of subjects
    415
    356
    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)
    394
    338
        From 65-84 years
    20
    17
        85 years and over
    1
    1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    47.0 ± 11.23
    47.7 ± 10.83
    Gender categorical
    Units: Subjects
        Female
    363
    324
        Male
    52
    32

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo was injected into the Glabellar Lines (GL) and latheral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the placebo in GL & LCL areas as defined in the protocol.

    Reporting group title
    MT10109L 20U in GL + Placebo in LCL
    Reporting group description
    MT10109L 20U was injected into the Glabellar Lines (GL) and Placebo into the Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving the MT10109L in GL & Placebo in LCL areas as defined in the protocol.

    Reporting group title
    MT10109L 20U GL + MT10109L 24 U LCL
    Reporting group description
    MT10109L 20U was injected into the Glabellar Lines (GL) and MT10109L 24U injected into Lateral Canthal Lines (LCL): initial double-blind treatment on Day 1. This arm describes the data for participants receiving MT10109L in GL & LCL areas as defined in the protocol.
    Reporting group title
    Retreatment 1 for Placebo arm
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.

    Reporting group title
    MT10109L 20U in GL + Placebo in LCL retreatment 1
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.

    Reporting group title
    MT10109L 20U GL + MT10109L 24 U LCL retreatment 1
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.
    Reporting group title
    Placebo retreatment 2
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.

    Reporting group title
    MT10109L 20U in GL + Placebo in LCL retreatment 2
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.

    Reporting group title
    MT10109L 20U GL + MT10109L 24 U LCL retreatment2
    Reporting group description
    During the retreatment period (from Day 180 through Day 330), participants who meet retreatment criteria received up to 2 blinded interventions of the same study intervention received in the first period (MT10109L 20 U, 44 U, or placebo). Based on individual variability in time to meet retreatment criteria, retreatment timepoints are not expected to be synchronized among all participants in this study.

    Subject analysis set title
    Demographic and other Baseline Characteristics - ITT
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    82 participants in the placebo group 173 participants in the MT10109L 20 U group 160 participants in the MT10109L 44 U group

    Subject analysis set title
    Demographic and other Baseline Characteristics -mITT
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    67 participants in the placebo group 155 participants in the MT10109L 20U group 134 participants in the MTL10109L 44U group

    Primary: 1.1 Co-primary Efficacy Endpoint: The Percentage of Participants Achieving None or Mild on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Day 30 of Treatment Cycle 1

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    End point title
    1.1 Co-primary Efficacy Endpoint: The Percentage of Participants Achieving None or Mild on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Day 30 of Treatment Cycle 1
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The data here presents the percentage of participants who had GL severity at maximum frown of none or mild based on investigator FWS rating at Cycle 1 Day 30. FWS is 4-point grading scale, where 0=none, 1=mild, 2=moderate, and 3=severe.
    End point type
    Primary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    155
    134
    Units: Participants
        number (not applicable)
    3
    115
    99
    Statistical analysis title
    Placebo VS MT10109L in GL + Placebo in LCL
    Comparison groups
    MT10109L 20U in GL + Placebo in LCL v Placebo
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    MT10109L in GL plus MT10109L in LCL VS Placebo
    Comparison groups
    MT10109L 20U GL + MT10109L 24 U LCL v Placebo
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Confidence interval

    Primary: 1.2 Co-primary Efficacy Endpoint:The Percentage of Participants Achieving None or Mild on the FWS according to Participant assessment in GL Severity at Maximum Frown at Day 30 of Treatment Cycle 1

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    End point title
    1.2 Co-primary Efficacy Endpoint:The Percentage of Participants Achieving None or Mild on the FWS according to Participant assessment in GL Severity at Maximum Frown at Day 30 of Treatment Cycle 1
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The data here presents the percentage of participants who had GL severity at maximum frown of none or mild based on participant FWS rating at Cycle 1 Day 30. FWS is 4-point grading scale, where 0=none, 1=mild, 2=moderate, and 3=severe.
    End point type
    Primary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    155
    134
    Units: Participants
        number (not applicable)
    2
    107
    82
    Statistical analysis title
    Placebo VS MT10109L in GL + Placebo in LCL
    Comparison groups
    Placebo v MT10109L 20U in GL + Placebo in LCL
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Confidence interval
    Statistical analysis title
    MT10109L in GL plus MT10109L in LCL VS Placebo
    Comparison groups
    Placebo v MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: 2.1 The Duration of GL Treatment Effect Estimated as the Median Time to Return to Moderate or Severe GL at Maximum Frown in Participants Who Achieved a Rating of None or Mild GL Severity at Maximum Frown at Day 30 According to Inv Assessment

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    End point title
    2.1 The Duration of GL Treatment Effect Estimated as the Median Time to Return to Moderate or Severe GL at Maximum Frown in Participants Who Achieved a Rating of None or Mild GL Severity at Maximum Frown at Day 30 According to Inv Assessment
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The investigator evaluates the participant's GL severity using a 4-grade FWS scale (0 to 3) where 0=none and 3 = severe. The outcome is measured as median time to loss of treatment effect (i.e., return to moderate or severe GL severity at maximum frown using the FWS).
    End point type
    Secondary
    End point timeframe
    Day 1 (first treatment) to Day 180
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    3
    109
    96
    Units: day
        median (inter-quartile range (Q1-Q3))
    157.0 (114 to 216)
    116.0 (85 to 149)
    97.0 (67 to 147)
    No statistical analyses for this end point

    Secondary: 2.2 Sec Eff Endpoint: The Percentage of Participants Reporting Mostly Satisfied/Very Satisfied on a 5-point Scale of Very Dissatisfied to Very Satisfied at Day 60 on the FLSQ Follow-up Version Item 5 for GL

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    End point title
    2.2 Sec Eff Endpoint: The Percentage of Participants Reporting Mostly Satisfied/Very Satisfied on a 5-point Scale of Very Dissatisfied to Very Satisfied at Day 60 on the FLSQ Follow-up Version Item 5 for GL
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The Satisfaction Question 5, grades facial line treatment satisfaction on a 5-point scale (-2 to 2) where - 2=Very dissatisfied and 2=Very satisfied.
    End point type
    Secondary
    End point timeframe
    Day 60
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    59
    141
    125
    Units: Participants
        number (not applicable)
    4
    101
    96
    No statistical analyses for this end point

    Secondary: 2.3 Sec Eff Endpoint: The Percentage of Participants with ≥20-point Improvement from Baseline at Day 30 on the FLSQ Impact Domain for GL

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    End point title
    2.3 Sec Eff Endpoint: The Percentage of Participants with ≥20-point Improvement from Baseline at Day 30 on the FLSQ Impact Domain for GL
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥20-point improvement from baseline on the FLSQ impact domain (eg, reported a good improvement of the facial lines negative impact) are presented here.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    66
    146
    129
    Units: Participants
        number (not applicable)
    14
    106
    88
    No statistical analyses for this end point

    Secondary: 2.4 Sec Eff Endpoint: The Percentage of Responders for Investigator Assessments of GL Severity at Rest Using the FWS Among Participants Who were Rated At least Mild at Rest at Baseline, Where a Responder was Defined as Achieving ≥1-grade Improvement

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    End point title
    2.4 Sec Eff Endpoint: The Percentage of Responders for Investigator Assessments of GL Severity at Rest Using the FWS Among Participants Who were Rated At least Mild at Rest at Baseline, Where a Responder was Defined as Achieving ≥1-grade Improvement
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥1-grade improvement from baseline GL severity at rest based on participant FWS rating is presented here. FWS is a 4-grade scale (0 to 3) where 0 = none and 3 = severe.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    64
    137
    122
    Units: Participants
        number (not applicable)
    8
    75
    89
    No statistical analyses for this end point

    Secondary: 2.5 Sec Eff Endpoint: The Percentage of Responders for Participant Assessments of GL Severity at Rest Using the FWS Among Participants Who were Rated At least Mild at Rest at Baseline, where a Responder was defined as Achieving ≥1-grade Improvement

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    End point title
    2.5 Sec Eff Endpoint: The Percentage of Responders for Participant Assessments of GL Severity at Rest Using the FWS Among Participants Who were Rated At least Mild at Rest at Baseline, where a Responder was defined as Achieving ≥1-grade Improvement
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥1-grade improvement from baseline GL severity at rest based on participant FWS rating is presented here. FWS is a 4-grade scale (0 to 3) where 0 = none and 3 = severe.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    64
    140
    122
    Units: Participants
        number (not applicable)
    6
    85
    89
    No statistical analyses for this end point

    Secondary: 2.6 Sec Eff Endpoint: The Percentage of Participants with a ≥20-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Total Score for GL

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    End point title
    2.6 Sec Eff Endpoint: The Percentage of Participants with a ≥20-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Total Score for GL
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥20-point improvement from baseline on the FLO-11 questionnaire for GL (eg, reported less emotional and appearance-related impacts of upper-facial lines) is presented here.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    66
    147
    129
    Units: Participants
        number (not applicable)
    9
    107
    95
    No statistical analyses for this end point

    Secondary: 2.7 Sec Eff Endpoint: The Percentage of Participants with a ≥4-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Item 2 for GL

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    End point title
    2.7 Sec Eff Endpoint: The Percentage of Participants with a ≥4-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Item 2 for GL
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥4-point improvement from baseline on the FLO-11 questionnaire item 2 for GL (eg, reported good improvement in the appearance of skin age) is presented here.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    66
    146
    127
    Units: Participants
        number (not applicable)
    8
    96
    79
    No statistical analyses for this end point

    Secondary: 2.8 Sec Eff Endpoint: The Percentage of Participants with a ≥4-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Item 5 for GL

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    End point title
    2.8 Sec Eff Endpoint: The Percentage of Participants with a ≥4-point Improvement from Baseline at Day 30 on the FLO-11 Questionnaire Item 5 for GL
    End point description
    All primary and secondary efficacy analyses for EU regulatory endpoints were carried out using the mITT population, which consisted of all randomized participants who had a baseline transformed FLO-11 questionnaire total score of ≤50. The percentage of participants who achieved a ≥4-point improvement from baseline on the FLO-11 questionnaire item 5 for GL (eg, reported good improvement in attractiveness) is presented here.
    End point type
    Secondary
    End point timeframe
    Day 30
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    66
    141
    126
    Units: Participants
        number (not applicable)
    5
    87
    71
    No statistical analyses for this end point

    Secondary: 2.9 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Systolic Blood Pressure (BP)

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    End point title
    2.9 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Systolic Blood Pressure (BP)
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    69
    151
    135
    Units: mm Hg
        arithmetic mean (standard deviation)
    2.5 ± 12.81
    0.0 ± 12.33
    -1.7 ± 12.26
    No statistical analyses for this end point

    Secondary: 2.10: Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Diastolic Blood Pressure (BP)

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    End point title
    2.10: Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Diastolic Blood Pressure (BP)
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    69
    151
    135
    Units: mm Hg
        arithmetic mean (standard deviation)
    -1.4 ± 7.81
    -0.9 ± 10.07
    -0.8 ± 8.64
    No statistical analyses for this end point

    Secondary: 2.11 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Respiratory rate

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    End point title
    2.11 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Respiratory rate
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    69
    151
    135
    Units: breath/min
        arithmetic mean (standard deviation)
    0.0 ± 2.13
    0.1 ± 2.28
    -0.2 ± 2.21
    No statistical analyses for this end point

    Secondary: 2.12 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Pulse Rate

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    End point title
    2.12 Secondary Safety Endpoint: Mean Change From Baseline in Vital Signs - Pulse Rate
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    69
    151
    135
    Units: beats/min
        arithmetic mean (standard deviation)
    -1.7 ± 11.25
    -1.0 ± 10.30
    -1.0 ± 8.93
    No statistical analyses for this end point

    Secondary: 2.13 Secondary Safety endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Heart Rate

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    End point title
    2.13 Secondary Safety endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Heart Rate
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: beats/min
        arithmetic mean (standard deviation)
    3.6 ± 9.79
    2.4 ± 8.41
    3.4 ± 9.51
    No statistical analyses for this end point

    Secondary: 2.14 Secondary Safety endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - PR Interval

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    End point title
    2.14 Secondary Safety endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - PR Interval
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    133
    Units: milliseconds
        arithmetic mean (standard deviation)
    -3.2 ± 14.41
    -0.5 ± 12.41
    -0.7 ± 11.13
    No statistical analyses for this end point

    Secondary: 2.15 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QRS Duration

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    End point title
    2.15 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QRS Duration
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: milliseconds
        arithmetic mean (standard deviation)
    0.9 ± 5.78
    1.1 ± 6.08
    0.8 ± 6.06
    No statistical analyses for this end point

    Secondary: 2.16 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QT Interval

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    End point title
    2.16 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QT Interval
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: milliseconds
        arithmetic mean (standard deviation)
    -10.4 ± 23.88
    -5.6 ± 21.00
    -8.0 ± 22.69
    No statistical analyses for this end point

    Secondary: 2.17 Secondary Safety Endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcB Interval

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    End point title
    2.17 Secondary Safety Endpoint: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcB Interval
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: milliseconds
        arithmetic mean (standard deviation)
    0.1 ± 15.50
    1.2 ± 18.92
    1.7 ± 17.65
    No statistical analyses for this end point

    Secondary: 2.18 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcF Interval

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    End point title
    2.18 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - QTcF Interval
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: milliseconds
        arithmetic mean (standard deviation)
    -3.5 ± 14.19
    -1.2 ± 15.91
    -1.8 ± 14.47
    No statistical analyses for this end point

    Secondary: 2.19 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - RR Interval

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    End point title
    2.19 Secondary Safety Endpoint Mean Change From Baseline in Electrocardiogram (ECG) Parameters - RR Interval
    End point description
    Change from baseline at study exit. All safety analyses were carried out using Safety Population which includes all subjects who received at least 1 study treatment injection.
    End point type
    Secondary
    End point timeframe
    Day 360 (Study exit) or Early exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    67
    152
    134
    Units: milliseconds
        arithmetic mean (standard deviation)
    -46.0 ± 113.98
    -31.0 ± 113.11
    -44.6 ± 122.53
    No statistical analyses for this end point

    Secondary: 2.20 Secondary Safety Endpoint Number of Participants With Binding and Neutralizing Antibodies

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    End point title
    2.20 Secondary Safety Endpoint Number of Participants With Binding and Neutralizing Antibodies
    End point description
    Only samples that tested positive in the binding antibody confirmatory assay were evaluated for neutralizing antibodies. The participants with positive neutralizing antibodies are only shown.
    End point type
    Secondary
    End point timeframe
    Baseline to Study Exit
    End point values
    Placebo MT10109L 20U in GL + Placebo in LCL MT10109L 20U GL + MT10109L 24 U LCL
    Number of subjects analysed
    82
    173
    160
    Units: Participants
        number (not applicable)
    0
    0
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The timeframe for AEs is from the first dose on Day 1 and up to 30 days after their last visit or study exit (Day 360 or early exit)
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Placebo in both GL & LCL

    Reporting group title
    MT10109L 20 U
    Reporting group description
    GL: MT10109L 20U + LCL: Placebo

    Reporting group title
    MT10109L 44 U
    Reporting group description
    GL: MT10109L 20U + LCL: MT10109L 24U

    Serious adverse events
    Placebo MT10109L 20 U MT10109L 44 U
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 82 (2.44%)
    3 / 174 (1.72%)
    5 / 159 (3.14%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 174 (0.57%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometriosis
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 174 (0.57%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 82 (0.00%)
    1 / 174 (0.57%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 82 (0.00%)
    0 / 174 (0.00%)
    1 / 159 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 82 (1.22%)
    0 / 174 (0.00%)
    0 / 159 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo MT10109L 20 U MT10109L 44 U
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 82 (9.76%)
    23 / 174 (13.22%)
    13 / 159 (8.18%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 82 (4.88%)
    14 / 174 (8.05%)
    6 / 159 (3.77%)
         occurrences all number
    4
    14
    6
    General disorders and administration site conditions
    Injection site pain
         subjects affected / exposed
    4 / 82 (4.88%)
    9 / 174 (5.17%)
    7 / 159 (4.40%)
         occurrences all number
    4
    9
    7

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Feb 2019
    Substantial, made to integrate feedback and recommendations from health authorities and improve clarity of study processes: • Clarified the primary objective and endpoint, added secondary objectives and efficacy and safety endpoints. • Added vital sign measurements, ECG assessments, and collection of blood samples for hematology and chemistry testing for Days 30 and 120. Vital sign measurements were added for 30 days after each retreatment; ECG assessments were added for the days of Retreatments 1 and 2 and 30 days after each retreatment. • Added text to clarify that collection of AEs at follow-up visits only applies to participants who received study intervention, added a new section related to which type of AESI were selected for this study, revised the timeframe for which to report nonserious AESIs, revised the duration after which an AE would not be counted as a TEAE, and added a paragraph describing analysis of TEAEs related to PDSOT and monitoring of PDSOT. • Revised the description of which pregnancy outcomes were considered SAEs. • Added statement in primary analyses describing the condition under which MT10109L 44 U was to be tested, added text describing imputation methods, replaced site with baseline GL severity at maximum frown as assessed by the clinician (investigator or subinvestigator) as stratification factors, added text to describe the methods of sensitivity analyses, provided details on the ranking order for hierarchical testing of MT10109L 20 U and MT10109L 44 U versus placebo for secondary analyses.

    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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