Clinical trial NCT03785145
Conditions: Lateral Canthal Lines
Sponsor: Medy-Tox
Start date: 2018-12-20; Completion date: 2021-01-25
Enrollment: 235 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the safety and efficacy of MT10109L in the treatment of lateral canthal lines (LCL) in participants with moderate to severe LCL.

Detailed description:

Arms: arm 1: MT10109L will be injected into the LCL: initial double-blind treatment on Day 1, and up to 2 open-label study interventions during the retreatment period. arm 2: Placebo will be injected into the LCL: initial double-blind treatment on Day 1.
Interventions: intervention 1: MT10109L intervention 2: Placebo
Intervention descriptions: intervention 1: MT10109L will be injected into the LCL. intervention 2: Placebo will be injected into the LCL.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL
Protocol MT10109L-002 AMD 4
MT10109L
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Title Page
Protocol Title: 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
Protocol Number: MT10109L-002
Amendment Number: Amendment 4
Product: MT10109L (NivobotulinumtoxinA)
Brief Protocol Title: MT10109L in the Treatment of Lateral Canthal Lines
Development Phase: 3
Regulatory Agency Identifying Numbers: IND Number 121473;
EudraCT Number 2014-005279-10
Refer to the final page of this protocol for electronic signature and date of approval.
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CONFIDENTIAL
Protocol MT10109L-002 AMD 4
MT10109L
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5.
Study Population
Participants in the current study have moderate to severe LCL at maximum smile, as specified in 
Section 5.1.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
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6.2.
Preparation/Handling/Storage/Accountability
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention.
2. Only participants enrolled in the study may receive study intervention, and only authorized 
site personnel may administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
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CONFIDENTIAL
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10.1.3.
Informed Consent Process

The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding the 
study.

Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 
local regulations, ICH guidelines, HIPAA requirements, where applicable, and the IRB/IEC 
or study center.

The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF.

Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study.

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.
Participants who are rescreened are required to sign a new ICF.
10.1.4.
Data Protection

Participants will be assigned a unique identifier. Any participant records or datasets that are 
transferred to the sponsor will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred.

The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.

The participant must be informed that his/her medical records may be examined by clinical 
quality assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
10.1.5.
Posting Clinical Study Data

Study data and information may be published in nonpromotional, peer-reviewed publications 
either by or on behalf of the sponsor. 

Clinical study reports, safety updates, and annual reports will be provided to regulatory 
authorities as required.

Company-sponsored study information and tabular study results will be posted on the US 
National Institutes of Health's website www.ClinicalTrials.gov and other publicly accessible 
sites
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Protocol MT10109L-002 AMD 4
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10.1.6.
Data Quality Assurance

All participant data relating to the study will be recorded on printed or eCRFs unless 
transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the eCRF.

The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.

The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.

The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.

Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.

Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator as stated in the clinical trial agreement. No records may be 
destroyed during the retention period without the written approval of the sponsor. No records 
may be transferred to another location or party without written notification to the sponsor.
10.1.7.
Source Documents

Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.

Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study.

Definition of what constitutes source data can be found in Section 4.0 of ICH E6, Good 
Clinical Practice: Consolidated Guidance and must follow ALCOA, ie, records must be 
attributable, legible, contemporaneous, original, and accurate.
10.1.8.
Study and Site Closure
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
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CONFIDENTIAL
Protocol MT10109L-002 AMD 4
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10.10.
Appendix 10: Protocol Amendment History
The protocol amendment summary of changes table for the current amendment is located 
directly before the table of contents.
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Electronic Signatures
User
Date
Justification
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SAP_001.pdf: 
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MT10109L-002 Statistical Analysis Plan Amendment 1
1.0
TITLE PAGE
MT10109L-002
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
STATISTICAL ANALYSIS PLAN - Clinical Study Report
[Final]: [18 NOV 2020]
Confidentiality Statement
This document is the property of Allergan, Inc., and may notin full or partbe passed on, 
reproduced, published, distributed to any person, or submitted to any regulatory authority
without the express written permission of Allergan, Inc.


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3.0
LIST OF ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
analysis of covariance
AST
aspartate aminotransferase
CMH
Cochran-Mantel-Haenszel
ECG
electrocardiogram
EU
European Union
FWS
Facial Wrinkle Scale with Photonumeric Guide 
ITT
intent to treat
LCL
lateral canthal lines
MCMC
Markov chain Monte Carlo
MedDRA
Medical Dictionary for Regulatory Activities
 
Q1
25th percentile
Q3
75th percentile
QTc
QT interval corrected for heart rate
QTcB
QT interval corrected for heart rate using the Bazett formula (QTcB = QT/(RR)½)
QTcF
QT interval corrected for heart rate using the Fridericia formula (QTcF = QT/(RR)⅓)
RBC
Red blood cell
SAE
serious adverse event
SAP
statistical analysis plan
SAS
Statistical Analysis Software
SI
Le Système International d’Unités (International System of Units)
TEAE
treatment-emergent adverse event
WBC
white blood cell




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5.0
OBJECTIVES
The objectives of this study are to evaluate the safety and efficacy between MT10109L and
placebo in the treatment of participants with moderate to severe LCL. 








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9.0
EXTENT OF EXPOSURE 
Participants’ exposure to study intervention will be summarized by total duration of treatment 
exposure and by cycle 
 
In addition, for the entire study, the number and percentage of participants 
receiving 1, 2, or 3 study interventions will be summarized.


















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11.2
CLINICAL LABORATORY PARAMETERS
Hematology and non-fasting blood chemistry assays will be collected at screening visit only and 
performed by a central laboratory. The clinical laboratory parameters include the following:
Hematology:
Hemoglobin, hematocrit, red blood cell count (RBC), RBC morphology,
white blood cell count (WBC), neutrophils, lymphocytes, monocytes, 
basophils, eosonophils, and platelets
Chemistry:
glucose, creatinine, urea nitrogen, total bilirubin, albumin, aspartate 
aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), 
alkaline phosphatase, uric acid, sodium, potassium, bicarbonate (carbon 
dioxide content), chloride, phosphorus, calcium, magnesium, and total protein.






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12.0
INTERIM ANALYSIS
No interim analysis is planned for this study.




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14.0
STATISTICAL SOFTWARE
Statistical analyses will be performed using version 9.3 (or newer) of SAS on a Linux operating 
system.




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PARAMETERS
If a participant has repeated assessments before the start of the first treatment, the results from 
the final nonmissing assessment made prior to the start of the study treatment will be used as 
baseline. If end-of-study assessments are repeated or if unscheduled visits occur, the last 
nonmissing postbaseline assessment will be used as the end-of-study assessment for generating 
summary statistics. 
15.6
MISSING SEVERITY ASSESSMENT FOR ADVERSE EVENTS
If severity is missing for an AE that started before the date of the first dose of study treatment, an 
intensity of mild will be assigned. If severity is missing for an AE that started on or after the date 
of the first dose of study treatment, an intensity of severe will be assigned. The imputed values 
for severity assessment will be used for the incidence summary; the values will be shown as 
missing in the data listings.
15.7
MISSING CAUSAL RELATIONSHIP TO STUDY INTERVENTION FOR 
ADVERSE EVENTS
If the causal relationship to the study intervention is missing for an AE that started on or after the 
date of the first dose of study treatment, a causality of yes will be assigned. The imputed values 
for causal relationship to study treatment will be used for the incidence summary; the values will 
be shown as missing in the data listings.


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15.8
MISSING DATE INFORMATION FOR ADVERSE EVENTS
Partial adverse event onset date will be imputed as follows:  1) if day is missing but month is not, 
impute the date as the first day of the month; 2) if both day and month are missing, impute the 
date as 01 Jan; 3) if imputed onset date is before the first treatment, yet the corresponding
adverse event was not observed pre-treatment, then impute the onset date as the first treatment 
date.  Imputed partial adverse event onset date will only be used to determine the adverse event 
onset cycle.
Other partial adverse event dates will not be imputed.  All partial dates will be listed “as is” in 
the data listings.
15.9
MISSING DATE INFORMATION FOR PRIOR OR CONCOMITANT
MEDICATIONS
There will be no imputation for missing or partially reported medication start and/or end dates. 
However, reported partial information will be utilized in classification of prior and concomitant 
medications, when appropriate. For example, a medication may be classified as a pre-study 
medication if the partial end date provided is determined to definitively have occurred prior to 
the study treatment date (for example, the partial end date provided is “2017”, and Day 1 
occurred on August 29, 2018).
If start and/or stop dates for medications are only partially reported but can be classified as 
having occurred prior to Day 1, then the medications will be included in this summary of prior 
medications.
If stop dates for medications are only partially reported and cannot be definitively classified as 
having occurred prior to Day 1, then the medications will be included in this summary of 
concomitant medications.




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REFERENCES
Dmitrienko A, Molenberghs G, Chuang-Stein C, Offen W. Gatekeeping strategies. In: Analysis
of clinical trials using SAS: a practical guide. Cary, NC: SAS Institute; 2005. p. 104-108.
O'Kelly M, Ratitch B. Clinical trials with missing data: A guide for practitioner. Statistics in
Practice. Wiley;2014.
Wilson EB, Hilferty, MM. The distribution of chi-squared. Proceedings of the National Academy
of Sciences, Washington. 1931;17:12,684-688.


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Electronic Signatures
User
Date
Justification