A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of Venglustat (GZ/SAR402671) in Parkinson's Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation (MOVES-PD)

• ClinicalTrials.gov Identifier: NCT02906020
• Recruitment Status: Terminated
• First Posted: September 19, 2016
• Results First Posted: February 28, 2022
• Last Update Posted: May 24, 2022
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease
• Interventions: Drug: venglustat GZ/SAR402671; Drug: Placebo
• Enrollment: 273

Participant Flow

Recruitment Details	Study was conducted at 52 sites in 16 countries. A total of 273 participants were enrolled from 15-Dec-2016 to 18-Dec-2019. Study consisted of 2 Parts: Part 1 (dose escalation period) & Part 2 (double-blind [DB] treatment period + long-term follow-up [LTFU]) period.
Pre-assignment Details	Post part 1 completion, 23 eligible & willing participants were re-randomized in Part 2 and were counted again in total enrollment number (273). i.e.,250 unique participants (29 in Part 1+221 in Part 2)+23 re-randomized in Part 2; these 23 participants are displayed only in 'participant flow' & 'adverse events' sections but not in any other section.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg	Part 2, DB Period: Placebo (Re-randomized From Part 1)	Part 2, DB Period: Venglustat 15 mg (Re-randomized From Part 1)	Part 2, LTFU Period: Placebo Then Venglustat 15 mg	Part 2, LTFU Period: Venglustat 15 mg	Part 2, LTFU: Placebo Then Veng 15 mg (Re-randomized From Part 1)	Part 2, LTFU: Venglustat 15 mg (Re-randomized From Part 1)
Arm/Group Description	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.	Participants who completed Part 1 with placebo (matched to venglustat) or venglustat 4/8/15 mg, met eligibility criteria for Part 2 and agreed to continue in the study, were re-randomized to receive placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants who completed Part 1 with placebo (matched to venglustat) or venglustat 4/8/15 mg, met eligibility criteria for Part 2 and agreed to continue in the study, were re-randomized to receive venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.	Participants who were enrolled in the study in Part 2, received placebo (matched to venglustat), completed Part 2 DB period, entered long-term follow-up (LTFU) period to receive venglustat 15 mg capsule orally QD for 156 weeks.	Participants who were enrolled in the study in Part 2, received venglustat 15 mg, completed Part 2 DB period, entered LTFU period to receive venglustat 15 mg capsule orally QD for 156 weeks.	Participants from Part 1 who were re-randomized in the study in Part 2, received placebo (matched to venglustat) and completed Part 2 DB period, entered LTFU period to receive venglustat (Veng) 15 mg capsule orally QD for 156 weeks.	Participants from Part 1 who were re-randomized in the study in Part 2, received venglustat 15 mg and completed Part 2 DB period, entered LTFU period to receive venglustat 15 mg capsule orally QD for 156 weeks.
Period Title: Part 1: Dose Escalation Period
Started	4	4	5	4	3	3	3	3	0	0	0	0	0	0	0	0
Treated	4	4	5	4	3	3	3	3	0	0	0	0	0	0	0	0
Completed	4	3	5	3	3	3	3	3	0	0	0	0	0	0	0	0
Not Completed	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Reason Not Completed
Adverse Event	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 2: Double-blind Treatment Period
Started	0	0	0	0	0	0	0	0	111	110	10	13	0	0	0	0
Treated	0	0	0	0	0	0	0	0	111	110	10	13	0	0	0	0
Completed	0	0	0	0	0	0	0	0	99	85	10	13	0	0	0	0
Not Completed	0	0	0	0	0	0	0	0	12	25	0	0	0	0	0	0
Reason Not Completed
Adverse Event	0	0	0	0	0	0	0	0	6	15	0	0	0	0	0	0
Other	0	0	0	0	0	0	0	0	6	10	0	0	0	0	0	0
Period Title: Part 2: Long-term Follow-up Period
Started	0	0	0	0	0	0	0	0	0	0	0	0	99	85	10	11 [1]
Treated	0	0	0	0	0	0	0	0	0	0	0	0	87	75	10	11
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not Completed	0	0	0	0	0	0	0	0	0	0	0	0	99	85	10	11
Reason Not Completed
Adverse Event	0	0	0	0	0	0	0	0	0	0	0	0	10	4	0	0
Progressive Disease	0	0	0	0	0	0	0	0	0	0	0	0	7	4	0	1
Lack of Efficacy	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Poor Compliance to Protocol	0	0	0	0	0	0	0	0	0	0	0	0	1	4	0	0
Study terminated by sponsor	0	0	0	0	0	0	0	0	0	0	0	0	67	64	7	8
Other	0	0	0	0	0	0	0	0	0	0	0	0	13	8	3	2
[1] Out of 13 completed participants in the previous part 2 DB period-arm, 2 didn't enter LTFU period.

Baseline Characteristics

Arm/Group Title		Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg	Total Title
Arm/Group Description		Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.	[Not Specified]
Overall Number of Baseline Participants		4	4	5	4	3	3	3	3	111	110	250
Baseline Analysis Population Description		Analysis was performed on all randomized unique participants (N=250) only.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	4 participants	4 participants	5 participants	4 participants	3 participants	3 participants	3 participants	3 participants	111 participants	110 participants	250 participants
		53.0 (8.8)	55.0 (3.9)	61.0 (6.9)	63.8 (8.7)	52.0 (10.4)	61.7 (5.9)	56.7 (4.0)	46.7 (8.1)	59.8 (8.5)	58.2 (9.8)	58.7 (9.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	5 participants	4 participants	3 participants	3 participants	3 participants	3 participants	111 participants	110 participants	250 participants
	Female	1 25.0%	1 25.0%	1 20.0%	1 25.0%	0 0.0%	3 100.0%	1 33.3%	1 33.3%	43 38.7%	45 40.9%	97 38.8%
	Male	3 75.0%	3 75.0%	4 80.0%	3 75.0%	3 100.0%	0 0.0%	2 66.7%	2 66.7%	68 61.3%	65 59.1%	153 61.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	5 participants	4 participants	3 participants	3 participants	3 participants	3 participants	111 participants	110 participants	250 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%	7 6.3%	10 9.1%	29 11.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	4 100.0%	4 100.0%	5 100.0%	4 100.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	104 93.7%	100 90.9%	221 88.4%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
Description	An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and does not necessarily had to have a causal relationship with the treatment. Serious AEs (SAEs) were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were the AEs that developed or worsened or became serious during the TEAE period (defined as the period from the time of first investigational medicinal product [IMP] administration up of 6 weeks after the last administration of the IMP).
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population which included both non-Japanese (ROW) and Japanese participants who received at least 1 dose of study medication in Part 1 of the study. This outcome measure (OM) was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE	4 100.0%	4 100.0%	4 80.0%	4 100.0%	2 66.7%	3 100.0%	3 100.0%	2 66.7%
Any TESAE	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

2. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Physical Examination Findings
Description	Physical examination included following observations/measurements: general appearance; heart, skin, respiratory auscultation; head, eyes, ears, nose, and throat, extremities/joints, and abdomen. New onset of abnormal physical examination was defined as a normal physical examination at Baseline and an abnormal physical examination during the treatment-emergent (TE) period (defined as the period from the time of first IMP administration up of 6 weeks after the last administration of the IMP). Abnormalities in physical examination were based on investigator's evaluation.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	1 20.0%	2 50.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

3. Primary Outcome

Title	Part 1: Number of Participants With Abnormal Neurological Examination Findings
Description	Neurological examination included at least assessments of the participant's cranial nerves, motor system (including muscle atrophy, tone, and power), mental status, deep tendon reflex, sensation, and cerebellar function. Abnormalities in neurological examination were based on investigator's evaluation.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Abnormal cranial nerve examination	1 25.0%	1 25.0%	1 20.0%	2 50.0%	1 33.3%	3 100.0%	3 100.0%	2 66.7%
Abnormal motor examination	3 75.0%	4 100.0%	4 80.0%	3 75.0%	3 100.0%	3 100.0%	3 100.0%	3 100.0%
Abnormal strength examination	1 25.0%	4 100.0%	3 60.0%	3 75.0%	1 33.3%	2 66.7%	2 66.7%	1 33.3%
Abnormal reflex examination	0 0.0%	1 25.0%	1 20.0%	1 25.0%	0 0.0%	2 66.7%	2 66.7%	0 0.0%
Abnormal sensory examination	0 0.0%	2 50.0%	0 0.0%	1 25.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%
Abnormal coordination examination	2 50.0%	1 25.0%	1 20.0%	3 75.0%	1 33.3%	0 0.0%	1 33.3%	2 66.7%
Abnormal gait and coordination	3 75.0%	4 100.0%	4 80.0%	2 50.0%	3 100.0%	2 66.7%	2 66.7%	2 66.7%

4. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematology
Description	Criteria for potentially clinically significant abnormalities (PCSA): Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (Male[M]) or <=95 g/L (Female[F]), greater than or equal to (>=) 185 g/L (M) or >=165 g/L (F), Decrease from baseline (DFB) >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) (M) or <=0.32 v/v (F), >=0.55 v/v (M) or >=0.5 v/v (F); Red blood cells (RBC): >=6 Tera/L; Platelets: less than (<) 100 Giga/L, >=700 Giga/L; White blood cells (WBC): <3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]), >=16.0 Giga/L; Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); Lymphocytes: <lower limit of normal (LLN), greater than (>) 4.0 Giga/L; Monocytes: <LLN, >0.7 Giga/L; Basophils: >0.1 Giga/L; Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L).
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Hemoglobin <= 115 g/L (M); ≤ 95 g/L (F)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hemoglobin >=185 g/L (M) or >=165 g/L (F)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hemoglobin DFB >=20 g/L	1 25.0%	0 0.0%	1 20.0%	1 25.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%
Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F)	0 0.0%	0 0.0%	1 20.0%	2 50.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Hematocrit: >=0.55 v/v (M); >=0.5 v/v (F)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
RBC: >=6 Tera/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Platelets: <100 Giga/L	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Platelets: >=700 Giga/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
WBC: <3.0 Giga/L (NB) or <2.0 Giga/L (B)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
WBC: >=16.0 Giga/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Lymphocytes: <LLN	0 0.0%	1 25.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%
Lymphocytes: >4.0 Giga/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Monocytes: <LLN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Monocytes: >0.7 Giga/L	0 0.0%	0 0.0%	2 40.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Basophils: >0.1 Giga/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

5. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Description	Criteria for PCSA: Alanine Aminotransferase (ALT): >3 ULN, >5 ULN; Aspartate aminotransferase (AST): >3 ULN; Alkaline phosphatase: >1.5 ULN; Total Bilirubin: >1.5 ULN; ALT and Bilirubin: >3 ULN and >2 ULN; Direct Bilirubin and Bilirubin: >35% and >1.5 ULN.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
ALT >3 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	1 33.3%	0 0.0%
ALT >5 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
AST >3 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%
AST >5 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Alkaline Phosphatase >1.5 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%
Total Bilirubin > 1.5 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
ALT and Bilirubin: >3 ULN and >2 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Direct Bilirubin and Bilirubin: >35% and >1.5 ULN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

6. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters
Description	Criteria for PCSA: Creatinine: >=150 micromoles per liter (mcmol/L) (adults), >=30% change from baseline, >=100% change from baseline; Blood urea nitrogen: >=17 millimoles (mmol)/L.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Creatinine >=150 mcmol/L (Adults)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Creatinine >=30% change from baseline	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%
Creatinine >=100% change from baseline	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Blood Urea Nitrogen >=17 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

7. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters
Description	Criteria for PCSA: Glucose: <=3.9 mmol/L and <LLN; >=11.1 mmol/L (unfasted [unfas]) or >=7 mmol/L (fasted [fas]); Albumin: <=25 g/L.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Glucose <=3.9 mmol/L and <LLN	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%
Albumin <=25 g/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

8. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters
Description	Criteria for PCSA: Sodium: <=129 mmol/L, >=160 mmol/L; Potassium: <3 mmol/L, >=5.5 mmol/L and Chloride: <80 mmol/L, >115 mmol/L.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Sodium <=129 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Sodium >=160 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Potassium <3 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Potassium >=5.5 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Chloride <80 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Chloride >115 mmol/L	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

9. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Description	Criteria for PCSA: Systolic blood pressure (SBP) supine: <=95 millimeters of mercury (mmHg) and DFB >=20 mmHg; >=160 mmHg and increase from baseline (IFB) >=20 mmHg; Diastolic blood pressure (DBP) supine: <=45 mmHg and DFB >=10 mmHg; >=110 mmHg and IFB >=10 mmHg; SBP (Orthostatic): <=-20 mmHg; DBP (Orthostatic): <=-10 mmHg; Heart rate (HR) supine: <=50 beats per minute (bpm) and DFB >=20 bpm; >=120 bpm and IFB >=20 bpm; Weight: >=5% DFB; >=5% IFB.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
SBP (supine) <=95 mmHg and DFB >=20 mmHg	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	2 66.7%	0 0.0%
SBP (supine) >=160 mmHg and IFB >=20 mmHg	0 0.0%	0 0.0%	0 0.0%	2 50.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP (supine) <=45 mmHg and DFB >=10 mmHg	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP (supine) >=110 mmHg and IFB >=10 mmHg	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
SBP (Orthostatic): <=-20 mmHg	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
DBP (Orthostatic): <=-10 mmHg	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
HR (supine) <=50 bpm and DFB >= 20 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
HR (supine) >=120 bpm and IFB >=20 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Weight >=5% DFB	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Weight >=5% IFB	1 25.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

10. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Ophthalmological Abnormalities
Description	Clinically significant observations in left eye, right eye and any eye (any eye among left and right) were assessed by the investigator based on methods like visual acuity, slit lamp examination, examination of the cornea, lens, and retina. Any abnormal clinically significant ophthalmological examination finding (which was present at screening or not) on any eye during the treatment-emergent period corresponded to cornea verticillata, cataract and abnormal overall evaluation
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Any eye	3 75.0%	3 75.0%	4 80.0%	2 50.0%	2 66.7%	3 100.0%	3 100.0%	0 0.0%
Right eye	3 75.0%	3 75.0%	4 80.0%	2 50.0%	2 66.7%	2 66.7%	3 100.0%	0 0.0%
Left eye	3 75.0%	3 75.0%	4 80.0%	2 50.0%	2 66.7%	3 100.0%	3 100.0%	0 0.0%

11. Primary Outcome

Title	Part 1: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities
Description	Criteria for PCSA: HR: <50 bpm; <50 bpm and DFB >=20 bpm, <40 bpm; >90 bpm, <90 bpm and IFB >=20 bpm, >100 bpm; PR Interval: >200 milliseconds (msec), >200 msec and IFB >=25%, >220 msec; QRS Interval: >110 msec, >110 msec and IFB >=25%, >120 msec; QT Interval: >500 msec; QTc Bazett (QTcB) interval: >450 msec, >480 msec, IFB >30 and <=60 msec, IFB >60 msec; QTc Fridericia (QTc F): >450 msec, >480 msec, IFB >30 and <=60 msec, IFB >60 msec.
Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., up to 42 weeks for ROW and up to 58 weeks for Japanese participants)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. This OM was planned to be analyzed and reported for Part 1 only and not for Part 2, as pre-specified in protocol.

Arm/Group Title	Part 1: Placebo (ROW)	Part 1: Venglustat 4 mg (ROW)	Part 1: Venglustat 8 mg (ROW)	Part 1: Venglustat 15 mg (ROW)	Part 1: Placebo (Japan Only)	Part 1: Venglustat 4 mg (Japan Only)	Part 1: Venglustat 8 mg (Japan Only)	Part 1: Venglustat 15 mg (Japan Only)
Arm/Group Description:	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.	Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.	Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.	Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.
Overall Number of Participants Analyzed	4	4	5	4	3	3	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
HR: <50 bpm	0 0.0%	1 25.0%	1 20.0%	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%
HR: <50 bpm and DFB >=20 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
HR: <40 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
HR: >90 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	1 33.3%
HR: >90 bpm and IFB >=20 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
HR: >100 bpm	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
PR Interval: >200 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 66.7%	0 0.0%	0 0.0%
PR Interval: >200 msec and IFB >=25%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
PR Interval: >220 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QRS Interval: >110 msec	0 0.0%	1 25.0%	1 20.0%	1 25.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QRS Interval: >110 msec and IFB >=25%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QRS Interval: >120 msec	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QT Interval: >500 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTcB interval: >450 msec	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTcB interval: >480 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTcB interval: IFB >30 and <=60 msec	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%
QTcB interval: IFB >60 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTc F: >450 msec	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTc F: >480 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
QTc F: IFB >30 and <=60 msec	0 0.0%	0 0.0%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%
QTc F: IFB >60 msec	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

12. Primary Outcome

Title	Part 2: Change From Baseline to Week 52 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II+III Total Score
Description	MDS-UPDRS is a multimodal scale consisting of 4 parts. Part II assessed motor experiences of daily living (total score range: 0 to 52). It contained 13 questions completed by the participant. Part III assessed the motor signs of PD and was administered by the rater (total score range: 0 to 132). Part III contained 33 scores based on 18 items. In both parts, higher score indicated more severe symptoms. For each question in both parts, numeric score was assigned between 0 to 4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS Total Part II and III score = sum of Part II and III scores with score ranged from 0 (no symptom) to 184 (severe symptoms), where higher scores reflected more severe symptoms of PD. Data for this OM was not planned to be collected and analyzed for Part 1, Part 2: DB period re-randomized participants and Part 2 LTFU period, as pre-specified in protocol.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Analyzed on intent-to-treat (ITT) population which included all randomized participants of Part 2 and analyzed in treatment group to which they were randomized. Here, overall number of participants analyzed = participants evaluable for this OM.

Arm/Group Title	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg
Arm/Group Description:	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.
Overall Number of Participants Analyzed	95	81
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	4.71 (1.27)	7.29 (1.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2, DB Period: Placebo, Part 2, DB Period: Venglustat 15 mg
	Comments	Least-squares (LS) mean, standard errors (SE) and p-value were estimated from mixed-effect model with repeated measures (MMRM) analysis which included fixed categorical effects of treatment group, randomization strata, time point, treatment-by-time point and strata-by-time point interaction and continuous fixed covariates Baseline value and Baseline value-by-time point interaction.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1679
	Comments	The threshold for statistical significance was 0.05.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.58
	Confidence Interval	(2-Sided) 95%; -1.10 to 6.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.87
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Part 2: Change From Baseline to Week 52 in Parkinson's Disease Cognitive Rating Scale (PD-CRS) Total Score
Description	The PD-CRS detects early cognitive impairment in Parkinson's disease. It is composed of 2 scales, the fronto-subcortical scale (items: sustained attention, working memory, alternating and action verbal fluency, clock drawing, immediate, and delayed free recall verbal memory) and the posterior-cortical scale (items: confrontation naming and clock copying). The total score of the fronto-subcortical scale (sum of all items) ranged from 0 (worst) to 104 (maximum score indicates better) and the total score of the posterior-cortical scale (sum of all items) ranged from 0 (worst) to 30 (maximum score indicates better). The PD-CRS Total score = the sum of PD-CRS fronto-subcortical score and the PD-CRS posterior-cortical score, which ranged from 0 to 134, where higher score = less impairment.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants evaluable for this OM. Data for this OM was not planned to be collected and analyzed for Part 1, Part 2: DB period re-randomized participants and Part 2 LTFU period, as pre-specified in protocol.

Arm/Group Title	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg
Arm/Group Description:	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.
Overall Number of Participants Analyzed	94	82
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	0.32 (1.27)	-0.65 (1.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2, DB Period: Placebo, Part 2, DB Period: Venglustat 15 mg
	Comments	LS mean, SE and P-value were estimated from MMRM analysis which included fixed categorical effects of treatment group, randomization strata, time point, treatment-by-time point and strata-by-time point interaction and continuous fixed covariates Baseline value and Baseline value-by-time point interaction.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.5996
	Comments	The threshold for statistical significance was 0.05.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -4.63 to 2.68
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.85
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Part 2: Change From Baseline to Week 52 in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I+ II+III Score
Description	MDS-UPDRS is a multimodal scale consisting of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (total score range: 0 to 52): Part IA contained 6 questions and was assessed by the examiner (total score range: 0 to 24). Part IB contained 7 questions on non-motor experiences of daily living which was completed by the participant (total score range: 0 to 28). Part II (13 questions completed by the participant) assessed motor experiences of daily living (total score range: 0 to 52). Part III assessed motor signs of PD and was administered by the rater (total score range: 0 to 132). Part III contained 33 scores based on 18 items. In all parts, higher score indicated more symptoms. For each question, numeric score was assigned between 0 to 4, where 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. MDS-UPDRS total score = sum of Parts I, II, and III (Range: 0 to 236). Higher score = more severe symptoms of PD.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants evaluable for this OM. Data for this OM was not planned to be collected and analyzed for Part 1, Part 2: DB period re-randomized participants and Part 2 LTFU period, as pre-specified in protocol.

Arm/Group Title	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg
Arm/Group Description:	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.
Overall Number of Participants Analyzed	95	81
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	5.87 (1.45)	9.99 (1.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2, DB Period: Placebo, Part 2, DB Period: Venglustat 15 mg
	Comments	LS mean, SE and P-value were estimated from MMRM analysis which included fixed categorical effects of treatment group, randomization strata, time point, treatment-by-time point and strata-by-time point interaction and continuous fixed covariates Baseline value and Baseline value-by-time-interaction
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0535
	Comments	The threshold for statistical significance was 0.05.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	4.13
	Confidence Interval	(2-Sided) 95%; -0.06 to 8.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.13
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Part 2: Change From Baseline to Week 52 in Hoehn and Yahr (H and Y) Score
Description	H and Y scale measured how Parkinson's symptoms progress and the level of disability. Scale allocated stage scores were from 0 to 5 to indicate relative level of disability as: Stage 0: no symptoms; Stage 1: symptoms on one side of the body only; Stage 2: symptoms on both sides of the body, without impairment of balance; Stage 3: Mild to moderate bilateral disease; some postural instability; physically independent; Stage 4: Severe disability; still able to walk or stand unassisted and Stage 5: Wheelchair bound or bedridden unless aided, where higher stage score described an increased severity of disease.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants evaluable for this OM. Data for this OM was not planned to be collected and analyzed for Part 1, Part 2: DB period re-randomized participants and Part 2 LTFU period, as pre-specified in protocol.

Arm/Group Title	Part 2, DB Period: Placebo	Part 2, DB Period: Venglustat 15 mg
Arm/Group Description:	Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.	Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.
Overall Number of Participants Analyzed	95	80
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	0.18 (0.05)	0.20 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2, DB Period: Placebo, Part 2, DB Period: Venglustat 15 mg
	Comments	LS mean, SE and P-value: estimated from MMRM analysis which included fixed categorical effects of treatment group, randomization strata, time point, treatment-by-time point and strata-by-time point interaction and continuous fixed covariates Baseline value and Baseline value-by-time-interaction.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.7400
	Comments	The threshold for statistical significance was 0.05.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	From the first IMP administration up to 6 weeks after the last administration of the IMP (i.e., in Part 1: up to 42 weeks for ROW, up to 58 weeks for Japanese participants; in Part 2 DB period: up to 60 weeks; in Part 2 LTFU period: up to 164 weeks).
Adverse Event Reporting Description	Reported AEs and deaths were TEAEs that developed/worsened in grade or became serious during TEAE period (defined as the time from the first dose of the IMP to the last dose of IMP + 6 weeks). Analysis was performed on safety population.
Arm/Group Title	Part 1: Placebo (ROW)		Part 1: Venglustat 4 mg (ROW)		Part 1: Venglustat 8 mg (ROW)		Part 1: Venglustat 15 mg (ROW)		Part 1: Placebo (Japan Only)		Part 1: Venglustat 4 mg (Japan Only)		Part 1: Venglustat 8 mg (Japan Only)		Part 1: Venglustat 15 mg (Japan Only)		Part 2, DB Period: Placebo		Part 2, DB Period: Venglustat 15 mg		Part 2, DB Period: Placebo (Re-randomized From Part 1)		Part 2, DB Period: Venglustat 15 mg (Re-randomized From Part 1)		Part 2, LTFU Period: Placebo Then Venglustat 15 mg		Part 2, LTFU Period: Venglustat 15 mg		Part 2, LTFU: Placebo Then Veng 15 mg (Re-randomized From Part 1)		Part 2, LTFU: Venglustat 15 mg (Re-randomized From Part 1)
Arm/Group Description	Participants from rest of world (ROW, except Japan), received placebo (matched to venglustat) capsule orally once daily (QD) for up to 36 weeks in Part 1.		Participants from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.		Participants from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.		Participants from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.		Japanese participants received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.		Japanese participants received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.		Japanese participants received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.		Japanese participants received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.		Participants received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.		Participants received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.		Participants who completed Part 1 with placebo (matched to venglustat) or venglustat 4/8/15 mg, met eligibility criteria for Part 2 and agreed to continue in the study, were re-randomized to receive placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.		Participants who completed Part 1 with placebo (matched to venglustat) or venglustat 4/8/15 mg, met eligibility criteria for Part 2 and agreed to continue in the study, were re-randomized to receive venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.		Participants who were enrolled in the study in Part 2, received placebo (matched to venglustat), completed Part 2 DB period, entered long-term follow-up (LTFU) period to receive venglustat 15 mg capsule orally QD for 156 weeks.		Participants who were enrolled in the study in Part 2, received venglustat 15 mg, completed Part 2 DB period, entered LTFU period to receive venglustat 15 mg capsule orally QD for 156 weeks.		Participants from Part 1 who were re-randomized in the study in Part 2, received placebo (matched to venglustat) and completed Part 2 DB period, entered LTFU period to receive venglustat (Veng) 15 mg capsule orally QD for 156 weeks.		Participants from Part 1 who were re-randomized in the study in Part 2, received venglustat 15 mg and completed Part 2 DB period, entered LTFU period to receive venglustat 15 mg capsule orally QD for 156 weeks.
All-Cause Mortality
	Part 1: Placebo (ROW)		Part 1: Venglustat 4 mg (ROW)		Part 1: Venglustat 8 mg (ROW)		Part 1: Venglustat 15 mg (ROW)		Part 1: Placebo (Japan Only)		Part 1: Venglustat 4 mg (Japan Only)		Part 1: Venglustat 8 mg (Japan Only)		Part 1: Venglustat 15 mg (Japan Only)		Part 2, DB Period: Placebo		Part 2, DB Period: Venglustat 15 mg		Part 2, DB Period: Placebo (Re-randomized From Part 1)		Part 2, DB Period: Venglustat 15 mg (Re-randomized From Part 1)		Part 2, LTFU Period: Placebo Then Venglustat 15 mg		Part 2, LTFU Period: Venglustat 15 mg		Part 2, LTFU: Placebo Then Veng 15 mg (Re-randomized From Part 1)		Part 2, LTFU: Venglustat 15 mg (Re-randomized From Part 1)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/4 (0.00%)		0/4 (0.00%)		0/5 (0.00%)		0/4 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		0/111 (0.00%)		1/110 (0.91%)		0/10 (0.00%)		0/13 (0.00%)		1/87 (1.15%)		0/75 (0.00%)		0/10 (0.00%)		0/11 (0.00%)
Serious Adverse Events
	Part 1: Placebo (ROW)		Part 1: Venglustat 4 mg (ROW)		Part 1: Venglustat 8 mg (ROW)		Part 1: Venglustat 15 mg (ROW)		Part 1: Placebo (Japan Only)		Part 1: Venglustat 4 mg (Japan Only)		Part 1: Venglustat 8 mg (Japan Only)		Part 1: Venglustat 15 mg (Japan Only)		Part 2, DB Period: Placebo		Part 2, DB Period: Venglustat 15 mg		Part 2, DB Period: Placebo (Re-randomized From Part 1)		Part 2, DB Period: Venglustat 15 mg (Re-randomized From Part 1)		Part 2, LTFU Period: Placebo Then Venglustat 15 mg		Part 2, LTFU Period: Venglustat 15 mg		Part 2, LTFU: Placebo Then Veng 15 mg (Re-randomized From Part 1)		Part 2, LTFU: Venglustat 15 mg (Re-randomized From Part 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0.00%)		0/4 (0.00%)		0/5 (0.00%)		0/4 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		0/3 (0.00%)		12/111 (10.81%)		12/110 (10.91%)		0/10 (0.00%)		3/13 (23.08%)		15/87 (17.24%)		9/75 (12.00%)		3/10 (30.00%)		1/11 (9.09%)
Blood and lymphatic system disorders
Anaemia † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Cardiac disorders
Atrial Fibrillation † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	1/75 (1.33%)	1	0/10 (0.00%)	0	0/11 (0.00%)	0
Cardiac Arrest † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Cardio-Respiratory Arrest † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Impaired Gastric Emptying † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Inguinal Hernia † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	1/13 (7.69%)	1	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Intestinal Obstruction † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Nausea † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Volvulus † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Infections and infestations
Abdominal Abscess † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Covid-19 † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	1/10 (10.00%)	1	0/11 (0.00%)	0
Colonic Abscess † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Diverticulitis † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Osteomyelitis † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Pneumonia † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	1/13 (7.69%)	1	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Sepsis † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	1/13 (7.69%)	1	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Subacute Endocarditis † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Urinary Tract Infection † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	1/13 (7.69%)	1	1/87 (1.15%)	2	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Injury, poisoning and procedural complications
Anastomotic Leak † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Fall † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	2	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Femoral Neck Fracture † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Intentional Overdose † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	1/11 (9.09%)	1
Post Lumbar Puncture Syndrome † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	2/111 (1.80%)	3	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Postoperative Delirium † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Radius Fracture † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	1/75 (1.33%)	1	0/10 (0.00%)	0	0/11 (0.00%)	0
Rib Fracture † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Skin Laceration † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Subdural Haematoma † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back Pain † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	1/75 (1.33%)	1	0/10 (0.00%)	0	0/11 (0.00%)	0
Muscle Rigidity † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Spinal Pain † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	1/75 (1.33%)	1	0/10 (0.00%)	0	0/11 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Breast Cancer Female † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Malignant Melanoma † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Malignant Melanoma In Situ † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Non-Small Cell Lung Cancer † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Ovarian Epithelial Cancer † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Prostate Cancer † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Nervous system disorders
Cerebellar Haemorrhage † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Cognitive Disorder † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	1/10 (10.00%)	1	0/11 (0.00%)	0
Freezing Phenomenon † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Lumbar Radiculopathy † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	1/75 (1.33%)	1	0/10 (0.00%)	0	0/11 (0.00%)	0
On And Off Phenomenon † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	1/87 (1.15%)	1	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Parkinson's Disease † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	0/110 (0.00%)	0	0/10 (0.00%)	0	0/13 (0.00%)	0	3/87 (3.45%)	4	1/75 (1.33%)	2	0/10 (0.00%)	0	0/11 (0.00%)	0
Posterior Reversible Encephalopathy Syndrome † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	0/13 (0.00%)	0	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Syncope † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	1/111 (0.90%)	1	3/110 (2.73%)	4	0/10 (0.00%)	0	0/13 (0.00%)	0	2/87 (2.30%)	2	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Transient Ischaemic Attack † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/111 (0.00%)	0	1/110 (0.91%)	1	0/10 (0.00%)	0	1/13 (7.69%)	1	0/87 (0.00%)	0	0/75 (0.00%)	0	0/10 (0.00%)	0	0/11 (0.00%)	0
Psychiatric disorders
Confusional State † 1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/5 (0.00%)	0	0/4 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0	0/3 (0.00%)	0