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 Lateral Canthal Lines With or Without Concurrent Treatment of Glabellar Lines
Summary
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EudraCT number |
2014-005302-38 |
Trial protocol |
DE |
Global end of trial date |
25 Jan 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Jan 2024
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First version publication date |
18 Jan 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MT10109L-006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03732833 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND Number: 121473 | ||
Sponsors
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Sponsor organisation name |
Medytox Inc
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Sponsor organisation address |
78, Gangni 1-gil, Ochang-eup, Cheongwon-gu, Cheongju-si, Korea, Republic of, 28126
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Public contact |
Young Ryu, Medytox Inc, 82 2-6901-5424,
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Scientific contact |
Gyungjin Heo, Medytox Inc, 82 2-6901-5839, gjheo@medytox.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Sep 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jan 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To compare the efficacy between 24 U MT10109L and placebo for the treatment of LCL (with or without concurrent 20 U treatment of GL) in participants with moderate to severe LCL and GL.
The total global enrollment (as presented in the "Population of Trial Subjects" below was 424, 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 350 participants (USA - 235 ; Canada -76 and; Germany - 39).
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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 Harmonization (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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Nov 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 93
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Country: Number of subjects enrolled |
United States: 279
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Country: Number of subjects enrolled |
Germany: 52
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Worldwide total number of subjects |
424
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EEA total number of subjects |
52
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
393
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From 65 to 84 years |
30
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85 years and over |
1
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Recruitment
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Recruitment details |
Participants were screened and recruited at sites in US, Canada and Germany. The data described here is for the Intent-to-Treat population. The Intent-to-treat (ITT) population consisted of all randomized participants. | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
424 met the inclusion/exclusion criterial and were randomized. | ||||||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
First treatment
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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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.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + Placebo in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection.
Placebo - 0 U per 0.1 ml.
MT10109L - 4 U per 0.1 ml
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + MT10109L in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection.
MT10109L - 4 U per 0.1 ml
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Period 2
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Period 2 title |
Re-treatment 1
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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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.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + Placebo in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection.
Placebo - 0 U per 0.1 ml.
MT10109L - 4 U per 0.1 ml
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + MT10109L in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection.
MT10109L - 4 U per 0.1 ml
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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 re-treatment criteria, were eligible to enter period 2 (re-treatment 1) |
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Period 3
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Period 3 title |
Re-treatment 2
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Is this the baseline period? |
No | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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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.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Sterile concentrate, Injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + Placebo in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
|
||||||||||||||||||||||||||||||||||||||||
Dosage and administration details |
The volume was 0.1 ml per injection.
Placebo - 0 U per 0.1 ml.
MT10109L - 4 U per 0.1 ml
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Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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Routes of administration |
Intramuscular use
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Dosage and administration details |
The volume was 0.1 ml per injection. Placebo - 0 U per 0.1 ml.
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Arm title
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MT10109L in LCL + MT10109L in GL | ||||||||||||||||||||||||||||||||||||||||
Arm description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
MT10109L
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection, Sterile concentrate
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||||||||||||||||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
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Dosage and administration details |
The volume was 0.1 ml per injection.
MT10109L - 4 U per 0.1 ml
|
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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 (re-treatment 1), who met the protocol-defined re-treatment criteria, were eligible to enter period 3 (re-treatment 2) |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L in LCL + Placebo in GL
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Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L in LCL + MT10109L in GL
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||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Demographic and other Baseline Characteristics - ITT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
424 participants were included in the Intent-To-Treat (ITT) population (86 participants in the placebo group; 171 participants in the MT10109L in LCL + Placebo in GL; and 167 participants in the MT10109L in LCL + MT10109L in GL group).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Demographic and other Baseline Characteristics - mITT
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
350 participants were included in the modified Intent-To-Treat (ITT) population (70 participants in the placebo group; 138 participants in the MT10109L in LCL + Placebo in GL; and 142 participants in the MT10109L in LCL + MT10109L in GL group).
|
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|
|
|||
End points reporting groups
|
|||
Reporting group title |
Placebo
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||
Reporting group title |
MT10109L in LCL + Placebo in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||
Reporting group title |
MT10109L in LCL + MT10109L in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||
Reporting group title |
MT10109L in LCL + Placebo in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||
Reporting group title |
MT10109L in LCL + MT10109L in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||
Reporting group title |
Placebo
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving the placebo in both LCL and GL areas. | ||
Reporting group title |
MT10109L in LCL + Placebo in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and placebo the GL area. | ||
Reporting group title |
MT10109L in LCL + MT10109L in GL
|
||
Reporting group description |
The overall participants were randomized 2:2:1 to the following arms to receive: • Placebo in both LCL and GL areas, or • MT10109L 24 U (24 U in LCL area, placebo in GL area), or • MT10109L 44 U (24 U in LCL area and 20 U in GL area), This arm describes the data for participants receiving MT10109L in the LCL area and MT10109L the GL area. | ||
Subject analysis set title |
Demographic and other Baseline Characteristics - ITT
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
424 participants were included in the Intent-To-Treat (ITT) population (86 participants in the placebo group; 171 participants in the MT10109L in LCL + Placebo in GL; and 167 participants in the MT10109L in LCL + MT10109L in GL group).
|
||
Subject analysis set title |
Demographic and other Baseline Characteristics - mITT
|
||
Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
350 participants were included in the modified Intent-To-Treat (ITT) population (70 participants in the placebo group; 138 participants in the MT10109L in LCL + Placebo in GL; and 142 participants in the MT10109L in LCL + MT10109L in GL group).
|
|
|||||||||||||
End point title |
Co-primary Efficacy endpoint: The % of Participants Achieving None or Mild on the FWS According to Investigator Assessment of LCL Severity at Maximum Smile 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 LCL severity at maximum smile 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
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
MT10109L in LCL vs Placebo | ||||||||||||
Comparison groups |
MT10109L in LCL + Placebo in GL v Placebo
|
||||||||||||
Number of subjects included in analysis |
208
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [1] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
|||||||||||||
Notes [1] - The equality of the proportions of responders was analyzed using the CMH tests stratified by LCL baseline severity. |
|||||||||||||
Statistical analysis title |
MT10109L in LCL plus MT10109L in GL vs Placebo | ||||||||||||
Comparison groups |
MT10109L in LCL + MT10109L in GL v Placebo
|
||||||||||||
Number of subjects included in analysis |
212
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [2] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
|||||||||||||
Notes [2] - The equality of the proportions of responders was analyzed using the CMH tests stratified by LCL baseline severity. |
|
|||||||||||||
End point title |
Primary Efficacy endpoint: The % of Participants Achieving None or Mild on the FWS According to Participant Assessment of LCL Severity at Maximum Smile 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 LCL severity at maximum smile 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
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
MT10109L in LCL vs Placebo | ||||||||||||
Comparison groups |
Placebo v MT10109L in LCL + Placebo in GL
|
||||||||||||
Number of subjects included in analysis |
208
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [3] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
|||||||||||||
Notes [3] - The equality of the proportions of responders was analyzed using the CMH tests stratified by LCL baseline severity. |
|||||||||||||
Statistical analysis title |
MT10109L in LCL plus MT10109L in GL vs Placebo | ||||||||||||
Comparison groups |
Placebo v MT10109L in LCL + MT10109L in GL
|
||||||||||||
Number of subjects included in analysis |
212
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [4] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
|||||||||||||
Notes [4] - The equality of the proportions of responders was analyzed using the CMH tests stratified by LCL baseline severity. |
|
|||||||||||||||||
End point title |
Sec Eff Endpoint 1: The Duration of LCL Treatment Effect Estimated as the Median Time to Return to Moderate or Severe LCL at Maximum Smile in Participants Who Achieved a Rating of None or Mild LCL Severity at Maximum Smile at Day 30 According to Inv Assmt | ||||||||||||||||
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 LCL 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 LCL severity at maximum smile using the FWS).
FWS is a 4-grade scale (0 to 3) where 0 = none and 3 = severe.
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Day 30
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 2: The % 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 LCL | ||||||||||||
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 3: The % of participants with ≥ 20-point improvement from baseline at Day 30 on the FLSQ Impact domain for LCL | ||||||||||||
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
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 4: The % of responders for Investigator assessments of LCL severity at rest using the FWS among participants who were rated at least mild at rest at baseline, where a responder is defined as achieving ≥ 1-grade improvement from baseline | ||||||||||||
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 LCL severity at rest based on investigator FWS rating is presented here.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 30
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 5: The % of responders for Participant assessments of LCL severity at rest using the FWS among participants who were rated at least mild at rest at baseline, where a responder is defined as achieving ≥ 1-grade improvement from baseline | ||||||||||||
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 LCL severity at rest based on participant FWS rating is presented here.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 30
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 6: The % of participants with a ≥ 20-point improvement from baseline at Day 30 on the FLO-11© questionnaire total score for LCL | ||||||||||||
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 LCL (eg, reported less emotional and appearance-related impacts of upper-facial lines) is presented here.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 30
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 7: The % of participants with a > 4-point improvement from baseline at Day 30 on the FLO-11 questionnaire Item 2 for LCL | ||||||||||||
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 LCL (eg, reported good improvement in the appearance of skin age) is presented here.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 30
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Eff Endpoint 8: The % of participants with a > 4-point improvement from baseline at Day 30 on the FLO-11 questionnaire Item 5 for LCL | ||||||||||||
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 LCL (eg, reported good improvement in attractiveness) is presented here.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 30
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 1a: Mean Change From Baseline in 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 1b: Mean Change From Baseline in 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 |
From Baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 2: Mean Change From Baseline in 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 |
Change from baseline to study exit at study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 3: Mean Change From Baseline in 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 |
Change from baseline to study exit at study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 4: Mean Change From Baseline in Electrocardiogram (ECG) Parameters - Mean 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 |
Change from baseline to study exit at day study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 5: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 6: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 7: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 8: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 9: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
End point title |
Sec Safety Endpoint 10: 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 |
Change from baseline to study exit
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sec Safety Endpoint 11: 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 |
On Day 360
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Treatment-Emergent Adverse Events (TEAEs) that started or worsened after the first dose of study intervention and within 30 days after the last visit or study exit (Day 360 unless the participant exits earlier)that started or worsened after the first dose
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Adverse event reporting additional description |
Treatment-Emergent Adverse Events (TEAEs)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo in both Lateral Canthal Lines (LCL) and Glabellar Lines (GL) areas | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L in LCL + Placebo in GL
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Reporting group description |
MT10109L was injected into the LCL and Placebo into the GL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L in LCL + MT10109L in GL
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Reporting group description |
MT10109L was injected into the LCL and MT10109L into the GL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Mar 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 applied 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 LCL severity at
maximum smile 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 24 U and MT10109L 44 U versus placebo for secondary analyses.
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |