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
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EudraCT number |
2014-005301-21 |
Trial protocol |
GB DE |
Global end of trial date |
22 Jan 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Feb 2024
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First version publication date |
15 Feb 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-005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03721016 | ||
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 2-69015424,
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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 |
22 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 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).
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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 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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Oct 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 |
United Kingdom: 23
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Country: Number of subjects enrolled |
Germany: 64
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Country: Number of subjects enrolled |
United States: 271
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Country: Number of subjects enrolled |
Canada: 57
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Worldwide total number of subjects |
415
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EEA total number of subjects |
64
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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) |
394
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From 65 to 84 years |
20
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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, UK, Germany and Canada. The data described here is for the ITT population. The ITT population consisted of all randomized participants. | ||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
505 patients were screened and 415 met the incusion/exclusion criteria 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 |
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
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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 |
Dosage - Placebo 0U per 0.1mL/injection
Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)
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Arm title
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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
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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 |
Dosage - MT10109L 4 U/0.1 mL/injection;
Administration - MT10109L in 5 GL sites; 0.1 mL/injection.
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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 |
Dosage - Placebo 0 U/0.1 mL/injection
Administration - Placebo in 6 LCL sites; 0.1 mL/injection.
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intramuscular use
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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)
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Period 2
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Period 2 title |
Retreatment 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 group 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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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
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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 |
Dosage - Placebo 0U per 0.1mL/injection
Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)
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Arm title
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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
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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 |
Dosage - MT10109L 4 U/0.1 mL/injection;
Administration - MT10109L in 5 GL sites; 0.1 mL/injection.
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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 |
Dosage - Placebo 0 U/0.1 mL/injection
Administration - Placebo in 6 LCL sites; 0.1 mL/injection.
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Arm title
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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
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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 |
Dosage - MT10109L 4 U/0.1 mL/injection;
Administration details - 11 injection sites (MT10109L in 5 GL sites + MT10109L in 6 LCL sites)
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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 retreatment criteria, were eligible to enter period 2 (Retreatment 1) |
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Period 3
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Period 3 title |
Retreatment 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 weere 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 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
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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 |
Dosage - Placebo 0U per 0.1mL/injection
Administration details - 11 injection sites (Placebo in 5 GL sites + Placebo in 6 LCL sites)
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Arm title
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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
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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 |
Dosage - MT10109L 4 U/0.1 mL/injection;
Administration - MT10109L in 5 GL sites; 0.1 mL/injection.
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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 |
Dosage - Placebo 0 U/0.1 mL/injection
Administration - Placebo in 6 LCL sites; 0.1 mL/injection.
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Arm title
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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
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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 |
Dosage - MT10109L 4 U/0.1 mL/injection;
Administration details - 11 injection sites (MT10109L in 5 GL sites + MT10109L in 6 LCL sites)
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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 (Retreatment1), who met the protocol-defined retreatment criteria, were eligible to enter period 3 (Retreatment 2) |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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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
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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
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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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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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 |
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
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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
|
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
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 |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
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 |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||
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
|
||||||||||||||||
|
|||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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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 GL & LCL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L 20 U
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Reporting group description |
GL: MT10109L 20U + LCL: Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MT10109L 44 U
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Reporting group description |
GL: MT10109L 20U + LCL: MT10109L 24U | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 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. |
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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 |