MT10109L in the Treatment of Lateral Canthal Lines

The primary efficacy measure is a composite endpoint and a participant is considered responder only if both the investigator and participant independently report a ≥ 2-grade improvement at Day 30 of Double-Blind Period from baseline. Both participant and investigator used FWS to assess GL severity. FWS is 4-grade scale (0 to 3): 0=none, 1=mild, 2=moderate and 3=severe

Time frame: Day 30

Population: All primary and secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis set, which was defined as all participants who were randomized. Multiple imputation method was used for missing variables in primary efficacy endpoint. Analyses of the secondary efficacy variables were performed using observed data.

The outcome reported here is the mean change in Diastolic BP from baseline to study exit.

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in mean heart rate from baseline to studyexit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in PR Interval from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QRS duration from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QTcB Interval from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QTcF Interval from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in QT Interval from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is a mean change in RR Interval from baseline to study exit

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Pulse Rate from baseline to study exit.

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Respiratory Rate from baseline to study exit.

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received. In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

The outcome reported here is the mean change in Systolic BP from baseline to study exit.

Time frame: Baseline to Day 360

Population: All safety analyses were carried out using the Safety population subset at study exit, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received.~In order to calculate the mean change from baseline, participants with non-missing analysis values at both baseline and post-baseline during that analysis visit were used.

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.

Time frame: Baseline to Day 360

Population: The immunogenicity was analyzed in Safety population, defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received.

This section focuses primarily on Treatment Emergent Adverse Events(TEAEs), i.e., AEs that started or worsened after the first dose of study intervention (Day 1) until up to 30 days after their last visit or study exit. TEAE's are recorded by the PI and their study team from observations made after treatment administration. The safety analyses were conducted in the Safety population. Unless otherwise noted, safety results refer to TEAEs. All safety analyses were performed with participants analyzed by their actual treatment or regimen received.

Time frame: AEs that started or worsen after the first dose of study intervention and up to 30 days after their last visit or study exit (Day 360 or early exit)

Population: All safety analyses were carried out using the Safety population set defined as participants who received at least 1 dose of study intervention. Participants were grouped based on their actual treatment received.~Please note: Participants in placebo group who entered open-label phase (post Day 180) and received study intervention (MT10109L) are counted in MT10109L group. Thus, overall number of participants in MT10109L group is greater than what is noted in participants flow.

The investigator evaluates the participant's LCL severity using a 4-grade scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3 = severe using the Facial Wrinkle Scale (FWS). 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).

Time frame: Day 1 (first treatment) to Day 180

Population: The analysis population for this outcome includes the participants who achieved a rating of ≥ 2-grade improvement from baseline in LCL severity at maximum smile at Day 30 according to investigator assessments using the Facial Wrinkle Scale (FWS). This corresponds to the responders for Outcome 2. Note: Analyses of the secondary efficacy variables were performed using observed data.

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.

Time frame: Day 60

Population: All secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis subset at day 60, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.

The Percentage of Responders for Investigator Assessments of Lateral Canthal Lines (LCL) Severity at Maximum Smile Using the Facial Wrinkle Scale (FWS), where a Responder was defined as Achieving a≥2-grade Improvement from Baseline at Maximum Smile at Day 30. The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe.

Time frame: Day 30

Population: All secondary efficacy analyses endpoints were carried out using the Intent-To-Treat (ITT) analysis subset at day 30, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.

The investigator evaluates the participant's LCL severity using a 4-point scale (0 to 3) where 0=none, 1=mild, 2=moderate and 3=severe. The outcome was measured among participants who were at least mild at rest at baseline, where a responder was defined as achieving a \>=1-grade improvement from baseline at Day 30.

Time frame: Day 30

Population: This secondary efficacy analysis was carried out using the Intent-To-Treat (ITT) analysis subset at day 30, which was defined as all participants who were randomized. Analyses of the secondary efficacy variables were performed using observed data.