Trial Outcomes & Findings for Study to Assess the Safety, Tolerability and Preliminary Efficacy of NLX-112 Versus Placebo in L-dopa-induced Dyskinesia (NCT NCT05148884)

NCT ID: NCT05148884

Last Updated: 2024-04-23

Results Overview

Number of patients with Adverse events (AEs) divided into categories of severity/intensity (grade 1 to grade 5 following the common terminology criteria for AEs (CTCAE) v5.0) and assessed relationship to IMP (unlikely, possibly or probably related). AEs (including SAEs) were collected from the start of IMP administration until the end-of-study visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: AEs (including SAEs) were collected from the start of IMP administration until the end-of-study visit. Through study completion, an average of 10 weeks.
• Results posted on: 2024-04-23

Participant Flow

Potential participants in the study were identified according to the routines of the clinical study sites. Patients were recruited at 5 clinical sites, with a planned average of 4 to 6 patients per site.

A total of 35 patients were screened and 27 were randomized and dosed in the study. Eighteen patients were allocated to treatment with NLX-112 and 9 were allocated to placebo. Twenty-three patients, 15 on NLX-112 and 8 on placebo, completed the study.

Participant milestones

Measure	NLX-112 Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112 oral tablets, uptitrated over 4 weeks to a maximal daily dose of 2 mg for 14 days given as 1mg two times a day.	Placebo Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Overall Study STARTED	18	9
Overall Study COMPLETED	15	8
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Measure	NLX-112 Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112 oral tablets, uptitrated over 4 weeks to a maximal daily dose of 2 mg for 14 days given as 1mg two times a day.	Placebo Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Overall Study Withdrawal by Subject	3	0
Overall Study Deep brain stimulation operation	0	1

Baseline Characteristics

Study to Assess the Safety, Tolerability and Preliminary Efficacy of NLX-112 Versus Placebo in L-dopa-induced Dyskinesia

Baseline characteristics by cohort

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.	Total n=27 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants	4 Participants n=4 Participants	12 Participants n=27 Participants
Age, Categorical >=65 years	10 Participants n=93 Participants	5 Participants n=4 Participants	15 Participants n=27 Participants
Age, Continuous	65.7 years STANDARD_DEVIATION 9.7 • n=93 Participants	64.6 years STANDARD_DEVIATION 6.3 • n=4 Participants	65.3 years STANDARD_DEVIATION 8.6 • n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	4 Participants n=4 Participants	12 Participants n=27 Participants
Sex: Female, Male Male	10 Participants n=93 Participants	5 Participants n=4 Participants	15 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=93 Participants	9 Participants n=4 Participants	26 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	17 Participants n=93 Participants	9 Participants n=4 Participants	26 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment Sweden	18 participants n=93 Participants	9 participants n=4 Participants	27 participants n=27 Participants

PRIMARY outcome

Timeframe: AEs (including SAEs) were collected from the start of IMP administration until the end-of-study visit. Through study completion, an average of 10 weeks.

Population: Full analysis set.

Number of patients with Adverse events (AEs) divided into categories of severity/intensity (grade 1 to grade 5 following the common terminology criteria for AEs (CTCAE) v5.0) and assessed relationship to IMP (unlikely, possibly or probably related). AEs (including SAEs) were collected from the start of IMP administration until the end-of-study visit.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Participants With Adverse Events (AEs) Is Life Threatening	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Severity - Moderate	10 Participants	4 Participants
Number of Participants With Adverse Events (AEs) Any AE	16 Participants	7 Participants
Number of Participants With Adverse Events (AEs) Any SAE	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Congenital Anomaly or Birth Defect	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Persistent or Significant Disability/Incapacity	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Requires or Prolongs Hospitalization	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Other Medically Important Serious Event	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE leading to withdrawal from study	1 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Any AE leading to death	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Causality - Unlikely Related	11 Participants	4 Participants
Number of Participants With Adverse Events (AEs) Causality - Possibly Related	15 Participants	5 Participants
Number of Participants With Adverse Events (AEs) Causality - Probably Related	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Action taken with study drug - Dose Not Changed	12 Participants	6 Participants
Number of Participants With Adverse Events (AEs) Action taken with study drug - Dose Reduced	4 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Action taken with study drug - Drug Interrupted	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Action taken with study drug - Not Applicable	5 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Severity - Mild	14 Participants	7 Participants
Number of Participants With Adverse Events (AEs) Severity - Severe	0 Participants	1 Participants
Number of Participants With Adverse Events (AEs) Severity - Life-Threatening	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) Severity - Death	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Visit 1 (Screening), Visit 2 (Baseline, Day 1), Visit 4 (Clinic Safety Visit, Day 14), Visit 5 (Clinic Safety Visit, Day 21), Visit 6 (Clinic Efficacy Visit, Day 28), Visit 7 (Clinic Efficacy Visit, Day 42) and Visit 9 (Follow-up Clinic Visit, Day 70).

Population: Full analysis set.

Number of patients with clinically significant changes from baseline in Electrocardiogram (Rate, PR interval, QRS duration, QT, QTcB, and QTcF). Any abnormalities were specified and documented as either clinically significant or not clinically significant.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Visit 1 (Screening), Visit 2 (Baseline, Day 1), Visit 4 (Clinic Safety Visit, Day 14), Visit 5 (Clinic Safety Visit, Day 21), Visit 6 (Clinic Efficacy Visit, Day 28), Visit 7 (Clinic Efficacy Visit, Day 42) and Visit 9 (Follow-up Clinic Visit, Day 70).

Population: Full analysis set.

Number of patients with clinically significant changes from baseline in vital signs (Systolic blood pressure (mmHg), diastolic blood pressure (mmHg), Heart rate, respiratory rate, body temperature). Any vital signs outside the normal ranges at each site were judged as either not clinically significant or clinically significant by the clinician.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Patients With Any Clinically Significant Changes From Baseline in Vital Signs	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Visit 1 (Screening), Visit 2 (Baseline, Day 1), Visit 4 (Clinic Safety Visit, Day 14), Visit 5 (Clinic Safety Visit, Day 21), Visit 6 (Clinic Efficacy Visit, Day 28), Visit 7 (Clinic Efficacy Visit, Day 42) and Visit 9 (Follow-up Clinic Visit, Day 70).

Population: Full analysis set.

Number of patients with clinically significant changes from baseline in safety laboratory parameters. Any lab values outside the normal ranges at each site were judged as not clinically significant or clinically significant.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Patients With Any Clinically Significant Changes From Baseline in Safety Laboratory Parameters	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Visit 1 (Screening) and Visit 9 (Follow-up Clinic Visit, Day 70).

Population: Full analysis set.

Number of patients with clinically significant abnormalities in physical examination investigated by general appearance, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, abdominal system, and nervous system. Any abnormalities were specified and documented as either clinically significant or not clinically significant.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Patients With Clinically Significant Abnormalities in Physical Examinations Visit 1	8 Participants	1 Participants
Number of Patients With Clinically Significant Abnormalities in Physical Examinations Visit 9	7 Participants	4 Participants

PRIMARY outcome

Timeframe: The baseline scale was used at screening (Visit 1) and the follow-up scale at all subsequent visits (Visit 2, 4-7, 9)

Population: Full analysis set.

Number of patients with change from baseline in suicidal ideation/behavior as assessed by C-SSRS questionnaire with no total score summation. The scale contains 6 "yes" or "no" questions in which respondents were asked to indicate whether they have experienced several thoughts or feelings relating to suicide over the past 3 months and behavior over their lifetime using a baseline scale at visit 1 and any cahnges since last visit using a follow-up scale at subsequent visits. Each question addresses a different component of the respondent's suicide ideation severity and behavior. Q1: wish to be dead, Q2: non-specific suicidal thoughts, Q3-5: more specific suicidal thoughts and intent to act, Q6: suicidal behavior over the respondent's lifetime and past 3 months or since last visit for visits after the visit 1.

Outcome measures

Measure	NLX-112 n=18 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Patients With Suicidal Ideation/Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At baseline (Day 1, Visit 2), and Day 42 (Visits 7)

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The Unified Dyskinesia Rating Scale (UDysRS) is a rating instrument designed to assess the core features of dyskinesia in Parkinson´s Disease. The UDysRS consists of 4 parts:

• Part 1, historical disability with regard to the patient's perceptions of the impact on activities of daily living (ADL) of on-dyskinesia (11 items).
• Part 2, historical disability with regard to the patient's perceptions of the impact on ADL of off-dystonia (4 items).
• Part 3, objective impairment, which assesses severity of dyskinesia, affected body parts, and type of impairment (choreic vs. dystonic) (7items).
• Part 4, objective disability, based on an evaluation of Part 3 activities (4 items).

Each item in the UDysRS was scored from 0 to 4, with a possible maximum total score sum of 104 where a higher score indicates a worse outcome.

The UDysRS Parts 3 and 4 were repeated 3 times after each L-dopa challenge, and the timepoint with the worst outcome was used to calculate total score sum

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline at the Final Efficacy Clinic Visit (Day 42), After a 150% L-dopa Dose Challenge, in the Unified Dyskinesia Rating Scale (UDysRS) Total Score - Change From Baseline Visit 2 Baseline	31.6 score on a scale Standard Deviation 9.7	39.9 score on a scale Standard Deviation 14.2
Change From Baseline at the Final Efficacy Clinic Visit (Day 42), After a 150% L-dopa Dose Challenge, in the Unified Dyskinesia Rating Scale (UDysRS) Total Score - Change From Baseline Visit 7 Clinic Efficacy Visit	25.3 score on a scale Standard Deviation 10.2	37.4 score on a scale Standard Deviation 12.8

SECONDARY outcome

Timeframe: At baseline (Day 1, Visit 2) and Day 28 (Visits 6)

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The Unified Dyskinesia Rating Scale (UDysRS) is a rating instrument designed to assess the core features of dyskinesia in Parkinson´s Disease. The UDysRS consists of 4 parts:

• Part 1, historical disability with regard to the patient's perceptions of the impact on activities of daily living (ADL) of on-dyskinesia (11 items).
• Part 2, historical disability with regard to the patient's perceptions of the impact on ADL of off-dystonia (4 items).
• Part 3, objective impairment, which assesses severity of dyskinesia, affected body parts, and type of impairment (choreic vs. dystonic) (7items).
• Part 4, objective disability, based on an evaluation of Part 3 activities (4 items).

Each item in the UDysRS was scored from 0 to 4, with a possible maximum total score sum of 104 where a higher score indicates a worse outcome.

The UDysRS Parts 3 and 4 were repeated 3 times after each L-dopa challenge, and the timepoint with the worst outcome was used to calculate total score sum

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in UDysRS Total Score at Day 28, After a 150% L-DOPA Dose Challenge - Change From Baseline Visit 2 Baseline	31.6 score on a scale Standard Deviation 9.7	39.9 score on a scale Standard Deviation 14.2
Change From Baseline in UDysRS Total Score at Day 28, After a 150% L-DOPA Dose Challenge - Change From Baseline Visit 6 Clinic Efficacy Visit	27.5 score on a scale Standard Deviation 11.2	37.9 score on a scale Standard Deviation 14.5

SECONDARY outcome

Timeframe: At baseline (Day 1, Visit 2), Day 28 and Day 42 (Visits 6 and 7)

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The Unified Dyskinesia Rating Scale (UDysRS) is a rating instrument designed to assess the core features of dyskinesia in Parkinson´s Disease. The UDysRS consists of 4 parts:

• Part 1, historical disability with regard to the patient's perceptions of the impact on activities of daily living (ADL) of on-dyskinesia (11 items).
• Part 2, historical disability with regard to the patient's perceptions of the impact on ADL of off-dystonia (4 items).
• Part 3, objective impairment, which assesses severity of dyskinesia, affected body parts, and type of impairment (choreic vs. dystonic) (7items).
• Part 4, objective disability, based on an evaluation of Part 3 activities (4 items).

Each item in the UDysRS was scored from 0 to 4, with a possible total score sum for parts 3 and 4 of 44, where a higher score indicates a worse outcome.

The UDysRS Parts 3 and 4 were repeated 3 times after each levodopa challenge, and the timepoint with the worst outcome was used to calculate total score sum.

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in Total Objective Score (Parts 3, 4) of the UDysRS at Day 28 and Day 42, After a 150% L-DOPA Dose Challenge - Change From Baseline Visit 2 Baseline	15.5 score on a scale Standard Deviation 6.2	18.1 score on a scale Standard Deviation 7.9
Change From Baseline in Total Objective Score (Parts 3, 4) of the UDysRS at Day 28 and Day 42, After a 150% L-DOPA Dose Challenge - Change From Baseline Visit 6 Clinic Efficacy Visit	13.8 score on a scale Standard Deviation 8.5	17.1 score on a scale Standard Deviation 7.2
Change From Baseline in Total Objective Score (Parts 3, 4) of the UDysRS at Day 28 and Day 42, After a 150% L-DOPA Dose Challenge - Change From Baseline Visit 7 Clinic Efficacy Visit	12.4 score on a scale Standard Deviation 7.2	18.0 score on a scale Standard Deviation 7.7

SECONDARY outcome

Timeframe: Baseline - prior to Day 1 (Visit 2), Titration - prior to Day 28 (Visit 6), and Steady state prior to Day 42 (Visit 7).

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

A PD Home Dyskinesia Diary (electronic) as completed by the patient and/or caregiver with concordance in ON time with dyskinesia between study staff and patient. The diary was integrated in the Kinesia 360 wearable dyskinesia assessment system and was based on the PD Home Diary developed by Hauser et al 2004. The diary was used to score 5 different conditions in 30-minute time intervals during 2x24 hours prior to Visit 2 (Baseline), Visit 6 (Titration) and Visit 7 (Steady state):

• ASLEEP;
• OFF;
• ON (i.e., adequate control of PD symptoms) without dyskinesia;
• ON with non-troublesome dyskinesia;
• ON with troublesome dyskinesia.

Presented as the ratio of ON Time without troublesome dyskinesia (the sum of the time in ON without dyskinesia together with the time in ON with non-troublesome dyskinesia) compared with the total awake time (ON and OFF).

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) Based on a PD Home Dyskinesia Diary - Change From Baseline Steady-State	0.648 Ratio time Standard Deviation 0.182	0.564 Ratio time Standard Deviation 0.206
Change From Baseline in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) Based on a PD Home Dyskinesia Diary - Change From Baseline Baseline	0.576 Ratio time Standard Deviation 0.199	0.548 Ratio time Standard Deviation 0.192
Change From Baseline in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) Based on a PD Home Dyskinesia Diary - Change From Baseline Titration	0.633 Ratio time Standard Deviation 0.133	0.591 Ratio time Standard Deviation 0.208

SECONDARY outcome

Timeframe: At baseline (Day 1, Visit 2), Day 28 (Visit 6), Day 42 (Visit 7) and Day 70 (Visit 9).

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The UPDRS is one of the most widely-used rating scales employed in the assessment of PD. The UPDRS consists of 4 parts:

• Part I assesses non-motor experiences of daily living, such as cognitive impairment and depressed mood (4 items).
• Part II assesses motor experiences of daily living, such as speech and eating tasks (13 items).
• Part III is a motor examination conducted by the clinician, including assessments of symptoms such as rigidity and tremor (27 items).
• Part IV is an assessment of motor complications, such as time spent with dyskinesia and functional impact of dyskinesias (11 items).

Each item in the UPDRS was scored from 0 to 4 (7 items in Part IV was scored 0 to 1), and the individual scores were summed to give a total score that indicates the severity of the disease, with a score of 0 indicating no disability and a score of 199 being the most severe (indicating total disability). Total score sum for Part III alone is 108.

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Scores (Part III, Motor Examination) - Change From Baseline Visit 2 Baseline	17.5 score on a scale Standard Deviation 9.4	17.0 score on a scale Standard Deviation 10.3
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Scores (Part III, Motor Examination) - Change From Baseline Visit 6 Clinic Efficacy Visit	13.9 score on a scale Standard Deviation 8.8	18.3 score on a scale Standard Deviation 11.5
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Scores (Part III, Motor Examination) - Change From Baseline Visit 7 Clinic Efficacy Visit	13.9 score on a scale Standard Deviation 8.5	17.1 score on a scale Standard Deviation 10.5
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Scores (Part III, Motor Examination) - Change From Baseline Visit 9 Follow-up Clinic Visit	14.8 score on a scale Standard Deviation 8.1	14.6 score on a scale Standard Deviation 9.0

SECONDARY outcome

Timeframe: At baseline (Day 1, Visit 2), Day 28 (Visit 6), Day 42 (Visit 7) and Day 70 (Visit 9).

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The UPDRS is one of the most widely-used rating scales employed in the assessment of PD. The UPDRS consists of 4 parts:

Part I assesses non-motor experiences of daily living, such as cognitive impairment and depressed mood (4 items).

Part II assesses motor experiences of daily living, such as speech and eating tasks (13 items).

Part III is a motor examination conducted by the clinician, including assessments of symptoms such as rigidity and tremor (27 items).

Part IV is an assessment of motor complications, such as time spent with dyskinesia and functional impact of dyskinesias (11 items).

Each item in the UPDRS was scored from 0 to 4 (7 items in Part IV was scored 0 to 1), and the individual scores were summed to give a total score that indicates the severity of the disease, with a score of 0 indicating no disability and a score of 199 being the most severe (indicating total disability).

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in UPDRS Combined Scores (Parts I, II, III and IV) - Change From Baseline Visit 2 Baseline	37.0 score on a scale Standard Deviation 13.3	41.3 score on a scale Standard Deviation 15.0
Change From Baseline in UPDRS Combined Scores (Parts I, II, III and IV) - Change From Baseline Visit 6 Clinic Efficacy Visit	30.5 score on a scale Standard Deviation 13.1	37.7 score on a scale Standard Deviation 12.5
Change From Baseline in UPDRS Combined Scores (Parts I, II, III and IV) - Change From Baseline Visit 7 Clinic Efficacy Visit	31.3 score on a scale Standard Deviation 13.9	37.4 score on a scale Standard Deviation 12.7
Change From Baseline in UPDRS Combined Scores (Parts I, II, III and IV) - Change From Baseline Visit 9 Follow-up Clinic Visit	32.6 score on a scale Standard Deviation 12.5	34.0 score on a scale Standard Deviation 14.3

SECONDARY outcome

Timeframe: Clinician rated the patient´s global condition using CGI-S at baseline (Day 1, Visit 2) and CGI-C at Day 28 (Visit 6) and Day 42 (Visit 7).

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The CGI-C is a clinician-oriented scale that assesses the total improvement in the patient's condition relative to the clinical global impression of severity (CGI-S) scale conducted at baseline.

1 - Normal not ill, 2 - Borderline ill, 3 - Mildly ill, 4 - Moderately ill, 5 - Markedly ill, 6- Severely ill, 7 - Among the most extremely ill patients The CGI-C rates the patient's condition from 1 to 7: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 2 Baseline - Normal, not at all ill	3 Participants	2 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 6 Clinic Efficacy Visit - Minimally worse	1 Participants	1 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 7 Clinic Efficacy Visit - Very much improved	1 Participants	0 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 7 Clinic Efficacy Visit - Much improved	4 Participants	1 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 2 Baseline - Moderately ill	8 Participants	2 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 2 Baseline - Markedly ill	3 Participants	2 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 2 Baseline - Severely ill	1 Participants	1 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 6 Clinic Efficacy Visit - Much improved	2 Participants	2 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 6 Clinic Efficacy Visit - Minimally improved	3 Participants	0 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 6 Clinic Efficacy Visit - No change	9 Participants	4 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 7 Clinic Efficacy Visit - Minimally improved	3 Participants	1 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 7 Clinic Efficacy Visit - No change	6 Participants	5 Participants
Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms Visit 7 Clinic Efficacy Visit - Minimally worse	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline - prior to Day 1 (Visit 2), Titration - prior to Day 28 (Visit 6), and Steady state prior to Day 42 (Visit 7).

Population: Per protocol analysis set (one patient excluded in placebo arm due to major protocol deviation).

The Kinesia 360 (Great Lakes Neurotechnologies, Inc) wearable dyskinesia assessment system was used to monitor dyskinesias. Sensors worn on the wrist and ankle combined with a mobile application continuously record data for assessment dyskinesia. Algorithms were used to detect symptoms from the motion sensors data and calculate a severity score (0 to 1 where score 0 corresponds to no dyskinesia and score 1 corresponds to dyskinesia) every 2 minutes. Wearable data collection of dyskinesia took place during a 2-day period prior to Visit 2 (Baseline), Visit 6 (Titration) and Visit 7 (Steady state). Outcome is presented as the mean ratio at baseline and absolute ratio change from baseline.

Outcome measures

Measure	NLX-112 n=15 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=7 Participants Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Change From Baseline in Dyskinesia Scores Measured by the Kinesia 360 (Great Lakes Neurotechnologies, Inc) Wearable Dyskinesia Assessment System - Absolute Change From Baseline Baseline	0.1807 score on a scale Standard Deviation 0.1955	0.2855 score on a scale Standard Deviation 0.3322
Change From Baseline in Dyskinesia Scores Measured by the Kinesia 360 (Great Lakes Neurotechnologies, Inc) Wearable Dyskinesia Assessment System - Absolute Change From Baseline Titration	-0.06517 score on a scale Standard Deviation 0.06722	-0.009172 score on a scale Standard Deviation 0.1353
Change From Baseline in Dyskinesia Scores Measured by the Kinesia 360 (Great Lakes Neurotechnologies, Inc) Wearable Dyskinesia Assessment System - Absolute Change From Baseline Steady-State	-0.009327 score on a scale Standard Deviation 0.1243	-0.01630 score on a scale Standard Deviation 0.3166

Adverse Events

NLX-112

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	NLX-112 n=18 participants at risk Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 participants at risk Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Nervous system disorders Syncope	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP

Other adverse events

Measure	NLX-112 n=18 participants at risk Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received NLX-112.	Placebo n=9 participants at risk Patients were randomized to receive either active treatment with NLX-112 or placebo. This arm represents the patients that received placebo.
Nervous system disorders Dizziness	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Dyskinesia	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Headache	16.7% 3/18 • Number of events 4 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	22.2% 2/9 • Number of events 3 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders On and off phenomenon	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Parkinsonism	16.7% 3/18 • Number of events 3 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	33.3% 3/9 • Number of events 7 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Parosmia	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Restless legs syndrome	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Somnolence	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Nervous system disorders Taste disorder	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Apathy	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Depression	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Dissociation	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Hallucination	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Illusion	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Insomnia	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Irritability	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Rapid eye movement sleep behavior disorder	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Sleep disorder	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Psychiatric disorders Stress	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Diarrhea	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Dry mouth	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Gastritis	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Nausea	22.2% 4/18 • Number of events 4 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Oral pain	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Gastrointestinal disorders Vomiting	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations COVID-19	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations Influenza	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations Nasopharyngitis	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	22.2% 2/9 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations Respiratory tract infection	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations Rhinitis	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Infections and infestations Urinary tract infection	5.6% 1/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Back pain	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Muscle spasms	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
General disorders Condition aggravated	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
General disorders Fatigue	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	22.2% 2/9 • Number of events 3 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Vascular disorders Hypertension	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Vascular disorders Orthostatic hypotension	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Vascular disorders Systolic hypertension	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Eye disorders Binocular eye movement disorder	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Eye disorders Dry eye	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Eye disorders Erythema of eyelid	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Eye disorders Eye pain	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Eye disorders Swelling of eyelid	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Ear and labyrinth disorders Tinnitus	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Ear and labyrinth disorders Vertigo	11.1% 2/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Injury, poisoning and procedural complications Fall	11.1% 2/18 • Number of events 3 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Injury, poisoning and procedural complications Incorrect dose administered	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Injury, poisoning and procedural complications Lip injury	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Injury, poisoning and procedural complications Product communication issue	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Renal and urinary disorders Micturition urgency	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Renal and urinary disorders Pollakiuria	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Cardiac disorders Palpitations	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Investigations Inflammatory marker increased	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Metabolism and nutrition disorders Hyperglycemia	5.6% 1/18 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/18 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	11.1% 1/9 • Number of events 1 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP
Surgical and medical procedures Cataract operation	5.6% 1/18 • Number of events 2 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP	0.00% 0/9 • AEs (including SAEs) were collected from the start of IMP administration (Visit 2) until the end-of-study visit (Visit 9), approximately 70 days. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0 \[24\]. AEs were assessed as unlikely, possibly or probably related to the IMP

Additional Information

Adrian Newman-Tancredi, PhD, DSc, CEO

Neurolixis

Phone: (+33) 605 14 09 64

Email: contact@neurolixis.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place