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Clinical Trial Results:
Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients with Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant.

Summary
EudraCT number	2016-000657-12
Trial protocol	SE DE AT ES PT IT GR
Global end of trial date	27 May 2021

Results information
Results version number	v2(current)
This version publication date	20 Jan 2023
First version publication date	21 Apr 2022
Other versions	v1
Version creation reason	Correction of full data set Updated safety optional field

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

ACT14820

ISRCTN number

US NCT number

NCT02906020

WHO universal trial number (UTN)

U1111-1180-6918

Sponsor organisation name

Genzyme Corporation, A Sanofi company

Sponsor organisation address

50 Binney Street, Cambridge, MA, United States, 02142

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

06 Aug 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 May 2021

Was the trial ended prematurely?

Yes

Main objective of the trial

To determine the safety and tolerability of 4, 8, and 15 milligrams (mg) of GZ/SAR402671, as compared to placebo, when administered orally daily for 4 weeks in early-stage Parkinson’s disease subjects carrying a glucocerebrosidase gene (GBA) mutation or other prespecified sequence variants (from now on both mutation types are referred to as ‘GBA mutation’). This allowed selection of the dose for the second part of this study (this did not apply to Japanese subjects).

Protection of trial subjects

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Dec 2016

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

36 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 2

Country: Number of subjects enrolled

Italy: 32

Country: Number of subjects enrolled

Japan: 22

Country: Number of subjects enrolled

Sweden: 8

Country: Number of subjects enrolled

Greece: 2

Country: Number of subjects enrolled

Singapore: 4

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Israel: 34

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Norway: 5

Country: Number of subjects enrolled

United States: 83

Country: Number of subjects enrolled

Germany: 15

Country: Number of subjects enrolled

Taiwan: 3

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

Spain: 13

Country: Number of subjects enrolled

Portugal: 4

Worldwide total number of subjects

250

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

182

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study was conducted at 52 sites in 16 countries. A total of 273 subjects 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.

Screening details

Post part 1 completion, 23 eligible & willing subjects were re-randomised in Part 2 and were counted again in total enrollment number (273) i.e.,250 unique subjects (29 in Part 1+221 in Part 2)+23 re-randomised in Part 2; these 23 subjects are displayed only in 'subject disposition' & 'adverse events' sections but not in any other section.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Are arms mutually exclusive

Part 1: Placebo (ROW)

Arm description

Subjects 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.

Arm type

Placebo

Investigational medicinal product name

Placebo for Part 1 (ROW)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo (matched to venglustat; per protocol) capsule orally QD in Part 1 up to 36 weeks for ROW.

Part 1: Venglustat 4 mg (ROW)

Arm description

Subjects from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1 (ROW)

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 4 mg (per protocol) capsule orally QD in Part 1, up to 36 weeks for ROW.

Part 1: Venglustat 8 mg (ROW)

Arm description

Subjects from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1 (ROW)

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 8 mg (per protocol) capsule orally QD in Part 1, up to 36 weeks for ROW.

Part 1: Venglustat 15 mg (ROW)

Arm description

Subjects from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1 (ROW)

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 1, up to 36 weeks for ROW.

Part 1: Placebo (Japan only)

Arm description

Japanese subjects received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.

Arm type

Placebo

Investigational medicinal product name

Placebo for Part 1 (Japan only)

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo (matched to venglustat; per protocol) capsule orally QD in Part 1, up to 52 weeks for Japanese subjects.

Part 1: Venglustat 4 mg (Japan only)

Arm description

Japanese subjects received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 4 mg (per protocol) capsule orally QD in Part 1, up to 52 weeks for Japanese subjects.

Part 1: Venglustat 8 mg (Japan only)

Arm description

Japanese subjects received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 8 mg (per protocol) capsule orally QD in Part 1, up to 52 weeks for Japanese subjects.

Part 1: Venglustat 15 mg (Japan only)

Arm description

Japanese subjects received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 1

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 1, up to 52 weeks for Japanese subjects.

Part 2, DB period: Placebo

Arm description

Subjects received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.

Arm type

Placebo

Investigational medicinal product name

Placebo for Part 2 DB period

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo (matched to venglustat; per protocol) capsule orally QD in Part 2 DB period for 52 weeks.

Part 2, DB period: Venglustat 15 mg

Arm description

Subjects received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 DB period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 DB period for 52 weeks.

Part 2, DB period: Placebo (Re-randomised from Part 1)

Arm description

Subjects 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-randomised to receive placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.

Arm type

Placebo

Investigational medicinal product name

Placebo for Part 2 DB period

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo (matched to venglustat; per protocol) capsule orally QD in Part 2 DB period for 52 weeks.

Part 2, DB Period: Venglustat 15mg (Re-randomised From Part 1)

Arm description

Subjects 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-randomised to receive venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 DB period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 DB period for 52 weeks.

Part 2, LTFU Period: Placebo Then Venglustat 15 mg

Arm description

Subjects 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.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 LTFU period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 LTFU for 156 weeks.

Part 2, LTFU Period: Venglustat 15 mg

Arm description

Subjects 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.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 LTFU period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 LTFU period for 156 weeks.

Part 2,LTFU:Placebo Then Veng 15mg (Re-randomised From Part 1)

Arm description

Subjects from Part 1 who were re-randomised 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.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 LTFU period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 LTFU for 156 weeks.

Part 2, LTFU: Venglustat 15 mg (Re-randomised From Part 1)

Arm description

Subjects from Part 1 who were re-randomised 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.

Arm type

Experimental

Investigational medicinal product name

Venglustat for Part 2 LTFU period

Investigational medicinal product code

GZ/SAR402671

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Venglustat 15 mg (per protocol) capsule orally QD in Part 2 LTFU period for 156 weeks.

Number of subjects in period 1	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-randomised from Part 1)	Part 2, DB Period: Venglustat 15mg (Re-randomised 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 15mg (Re-randomised From Part 1)	Part 2, LTFU: Venglustat 15 mg (Re-randomised From Part 1)
Started	4	4	5	4	3	3	3	3	111	110	10	13	99	85	10	11
Treated	4	4	5	4	3	3	3	3	111	110	10	13	87	75	10	11
Completed	4	3	5	3	3	3	3	3	99	85	10	13	0	0	0	0
Not completed	0	1	0	1	0	0	0	0	12	25	0	0	99	85	10	11
Other	-	-	-	-	-	-	-	-	6	10	-	-	13	8	3	2
Progressive Disease	-	-	-	-	-	-	-	-	-	-	-	-	7	4	-	1
Adverse event	-	1	-	1	-	-	-	-	6	15	-	-	10	4	-	-
Study terminated by sponsor	-	-	-	-	-	-	-	-	-	-	-	-	67	64	7	8
Poor Compliance to Protocol	-	-	-	-	-	-	-	-	-	-	-	-	1	4	-	-
Lack of efficacy	-	-	-	-	-	-	-	-	-	-	-	-	1	1	-	-

Baseline characteristics

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Reporting group title

Overall Study

Reporting group description

Reporting group values	Overall Study	Total
Number of subjects	250	250
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	58.7 ( 9.1 )	-
Gender categorical
Units: Subjects
Female	97	97
Male	153	153
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0
Asian	29	29
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	0	0
White	221	221
More than one race	0	0
Unknown or Not Reported	0	0

End points

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Reporting group title

Part 1: Placebo (ROW)

Reporting group description

Subjects 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.

Reporting group title

Part 1: Venglustat 4 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Venglustat 8 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Venglustat 15 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Placebo (Japan only)

Reporting group description

Japanese subjects received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 4 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 8 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 15 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 2, DB period: Placebo

Reporting group description

Subjects received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, DB period: Venglustat 15 mg

Reporting group description

Subjects received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, DB period: Placebo (Re-randomised from Part 1)

Reporting group description

Reporting group title

Part 2, DB Period: Venglustat 15mg (Re-randomised From Part 1)

Reporting group description

Subjects 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-randomised to receive venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, LTFU Period: Placebo Then Venglustat 15 mg

Reporting group description

Reporting group title

Part 2, LTFU Period: Venglustat 15 mg

Reporting group description

Subjects 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.

Reporting group title

Part 2,LTFU:Placebo Then Veng 15mg (Re-randomised From Part 1)

Reporting group description

Reporting group title

Part 2, LTFU: Venglustat 15 mg (Re-randomised From Part 1)

Reporting group description

Primary: Part 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

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End point title

Part 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs) ^[1] ^[2]

End point description

Adverse event (AE): defined as any untoward medical occurrence in a subject who received study drug and does not necessarily had to have a causal relationship with treatment. Serious AEs (SAEs): any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalisation, 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 period from the time of 1st investigational medicinal product [IMP] administration up of 6 weeks after last administration of IMP). Analysed on safety population which included both non-Japanese (ROW) and Japanese subjects who received at least 1 dose of study medication in Part 1 of study. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Any TEAE	4	4	4	4	2	3	3	2
Any TESAE	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Abnormal Physical Examination Findings

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End point title

Part 1: Number of Subjects With Abnormal Physical Examination Findings ^[3] ^[4]

End point 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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects	0	0	1	2	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Abnormal Neurological Examination Findings

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End point title

Part 1: Number of Subjects With Abnormal Neurological Examination Findings ^[5] ^[6]

End point description

Neurological examination included at least assessments of the subject'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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Abnormal cranial nerve examination	1	1	1	2	1	3	3	2
Abnormal motor examination	3	4	4	3	3	3	3	3
Abnormal strength examination	1	4	3	3	1	2	2	1
Abnormal reflex examination	0	1	1	1	0	2	2	0
Abnormal sensory examination	0	2	0	1	0	1	0	0
Abnormal coordination examination	2	1	1	3	1	0	1	2
Abnormal gait and coordination	3	4	4	2	3	2	2	2

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Hematology

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Hematology ^[7] ^[8]

End point description

Criteria for potentially clinically significant abnormalities (PCSA): Hemoglobin: less than or equal to (<=) 115 grams per litre (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 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). Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Hemoglobin <= 115 g/L (M); <=95 g/L (F)	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
Hemoglobin DFB >=20 g/L	1	0	1	1	0	0	0	1
Hematocrit: <=0.37 v/v (M) or <=0.32 v/v (F)	0	0	1	2	0	0	0	0
Hematocrit: >=0.55 v/v (M); >=0.5 v/v (F)	0	0	0	0	0	0	0	0
RBC: >=6 Tera/L	0	0	0	0	0	0	0	0
Platelets: <100 Giga/L	0	0	1	0	0	0	0	0
Platelets: >=700 Giga/L	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
WBC: >=16.0 Giga/L	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
Lymphocytes: <LLN	0	1	0	0	0	0	1	0
Lymphocytes: >4.0 Giga/L	0	0	0	0	0	0	0	0
Monocytes: <LLN	0	0	0	0	0	0	0	0
Monocytes: >0.7 Giga/L	0	0	2	0	0	0	0	0
Basophils: >0.1 Giga/L	0	0	0	0	0	0	0	0
Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5Giga/L)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ^[9] ^[10]

End point description

Criteria for PCSA: Alanine Aminotransferase (ALT): >3 ULN, >5 ULN; Aspartate aminotransferase (AST): >3*ULN; Alkaline phosphatase (ALP): >1.5*ULN; Total Bilirubin: >1.5 ULN; ALT and Bilirubin: >3 ULN and >2 ULN; Direct Bilirubin (DB) and Bilirubin: >35% and >1.5 ULN. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
ALT >3 ULN	0	0	0	0	1	0	1	0
ALT >5 ULN	0	0	0	0	0	0	0	0
AST >3 ULN	0	0	0	0	1	0	0	0
AST >5 ULN	0	0	0	0	0	0	0	0
ALP >1.5 ULN	0	0	0	0	1	0	0	0
Total Bilirubin > 1.5 ULN	0	0	0	0	0	0	0	0
ALT and Bilirubin: >3 ULN and >2 ULN	0	0	0	0	0	0	0	0
DB and B: >35% and >1.5 ULN	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters ^[11] ^[12]

End point description

Criteria for PCSA: Creatinine: >=150 micromoles per litre (mcmol/L) (adults [A]), >=30% change from baseline, >=100% change from baseline; Blood urea nitrogen (BUN): >=17 millimoles (mmol)/L. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Creatinine >=150 mcmol/L (A)	0	0	0	0	0	0	0	0
Creatinine >=30% change from baseline	0	0	0	0	0	0	1	0
Creatinine >=100% change from baseline	0	0	0	0	0	0	0	0
BUN >=17 mmol/L	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters ^[13] ^[14]

End point 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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Glucose <=3.9 mmol/L and <LLN	0	0	0	0	0	0	0	0
Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas)	0	0	0	0	0	1	0	0
Albumin <=25 g/L	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters ^[15] ^[16]

End point 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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Sodium <=129 mmol/L	0	0	0	0	0	0	0	0
Sodium >=160 mmol/L	0	0	0	0	0	0	0	0
Potassium <3 mmol/L	0	0	0	0	0	0	0	0
Potassium >=5.5 mmol/L	0	0	0	0	0	0	0	0
Chloride <80 mmol/L	0	0	0	0	0	0	0	0
Chloride >115 mmol/L	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities ^[17] ^[18]

End point description

Criteria for PCSA: Systolic blood pressure (SBP) supine: <=95 millimetres 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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
SBP (supine) <=95 mmHg and DFB >=20 mmHg	0	0	1	0	0	0	2	0
SBP (supine) >=160 mmHg and IFB >=20 mmHg	0	0	0	2	0	0	0	0
DBP (supine) <=45 mmHg and DFB >=10 mmHg	0	0	0	0	0	0	0	0
DBP (supine) >=110 mmHg and IFB >=10 mmHg	0	0	0	0	0	0	0	0
SBP (Orthostatic): <=-20 mmHg	0	0	0	0	0	0	0	0
DBP (Orthostatic): <=-10 mmHg	0	0	0	0	0	0	0	0
HR (supine) <=50 bpm and DFB >= 20 bpm	0	0	0	0	0	0	0	0
HR (supine) >=120 bpm and IFB >=20 bpm	0	0	0	0	0	0	0	0
Weight >=5% DFB	0	0	1	0	0	0	0	0
Weight >=5% IFB	1	0	1	0	0	0	0	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Ophthalmological Abnormalities

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Ophthalmological Abnormalities ^[19] ^[20]

End point description

Clinically significant observations in left eye, right eye and any eye were assessed by the investigator based on methods like visual acuity, slit lamp examination, examination of the cornea, lens, and retina. Any abnormal 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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
Any eye	3	3	4	2	2	3	3	0
Right eye	3	3	4	2	2	2	3	0
Left eye	3	3	4	2	2	3	3	0

No statistical analyses for this end point

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Electrocardiogram Abnormalities

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End point title

Part 1: Number of Subjects With Potentially Clinically Significant Electrocardiogram Abnormalities ^[21] ^[22]

End point 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 (Int): >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. Analysis was performed on safety population. This endpoint was planned to be analysed and reported for Part 1 only and not for Part 2, as pre-specified in the protocol.

End point type

Primary

End point timeframe

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 subjects)

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: As the endpoint was descriptive in nature, no statistical analysis was provided.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	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)
Number of subjects analysed	4	4	5	4	3	3	3	3
Units: subjects
HR: <50 bpm	0	1	1	0	1	0	0	0
HR: <50 bpm and DFB >=20 bpm	0	0	0	0	0	0	0	0
HR: <40 bpm	0	0	0	0	0	0	0	0
HR: >90 bpm	0	0	0	0	0	0	1	1
HR: >90 bpm and IFB >=20 bpm	0	0	0	0	0	0	0	0
HR: >100 bpm	0	0	0	0	0	0	0	0
PR Int: >200 msec	0	0	0	0	0	2	0	0
PR Int:>200 msec and IFB >=25%	0	0	0	0	0	0	0	0
PR Int: >220 msec	0	0	0	0	0	0	0	0
QRS Int: >110 msec	0	1	1	1	0	0	0	0
QRS Int:>110 msec and IFB >=25%	0	0	0	0	0	0	0	0
QRS Int: >120 msec	0	0	1	0	0	0	0	0
QT Int: >500 msec	0	0	0	0	0	0	0	0
QTcB Int: >450 msec	0	0	1	0	0	0	0	0
QTcB Int: >480 msec	0	0	0	0	0	0	0	0
QTcB Int:IFB >30 and <=60 msec	0	0	1	0	0	0	0	1
QTcB Int: IFB >60 msec	0	0	0	0	0	0	0	0
QTc F: >450 msec	0	0	1	0	0	0	0	0
QTc F: >480 msec	0	0	0	0	0	0	0	0
QTc F: IFB >30 and <=60 msec	0	0	1	0	0	0	0	1
QTc F: IFB >60 msec	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: 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

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End point 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 ^[23]

End point description

MDS-UPDRS: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 subject. Part III assessed motor signs of PD and was administered by rater (total score range:0 to 132). Part III had 33 scores based on 18 items. In both parts, higher score=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=more severe symptoms of PD. This endpoint was not planned to be collected and analysed for Part 1, Part 2 DB period re-randomised subjects and Part 2 LTFU period, as pre-specified in the protocol. Intent-to-treat population:all randomised subjects of Part 2 and analysed in randomised treatment group. number of subjects analysed=subjects evaluable.

End point type

Primary

End point timeframe

Baseline to Week 52

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	Part 2, DB period: Placebo	Part 2, DB period: Venglustat 15 mg
Number of subjects analysed	95	81
Units: units on a scale
least squares mean (standard error)	4.71 ( 1.27 )	7.29 ( 1.36 )

Part 2 DB period: Venglustat 15mg versus Placebo

Statistical analysis description

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, randomisation 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.

Comparison groups

Part 2, DB period: Venglustat 15 mg v Part 2, DB period: Placebo

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1679 ^[24]

Method

MMRM

Parameter type

LS mean difference

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

6.27

Variability estimate

Standard error of the mean

Dispersion value

1.87

Notes
[24] - The threshold for statistical significance was 0.05.

Secondary: Part 2: Change From Baseline to Week 52 in Parkinson's Disease Cognitive Rating Scale (PD-CRS) Total score

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End point title

Part 2: Change From Baseline to Week 52 in Parkinson's Disease Cognitive Rating Scale (PD-CRS) Total score ^[25]

End point description

PD-CRS detects early cognitive impairment in Parkinson's disease. It is composed of 2 scales, fronto-subcortical scale (items: sustained attention, working memory, alternating and action verbal fluency, clock drawing, immediate and delayed free recall verbal memory) and posterior-cortical scale (items: confrontation naming and clock copying). Total score of fronto-subcortical scale (sum of all items) ranged from 0 (worst) to 104 (maximum score indicates better) and total score of posterior-cortical scale (sum of all items) ranged from 0 (worst) to 30 (maximum score indicates better). PD-CRS Total score=sum of PD-CRS fronto-subcortical score and PDCRS posterior-cortical score, which ranged from 0 to 134, where higher score=less impairment. ITT population. Here, number of subjects analysed=subjects evaluable for this endpoint. This OM was not planned to be collected and analysed for Part 1, Part 2 DB period re-randomised subjects and Part 2 LTFU period, as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Baseline to Week 52

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	Part 2, DB period: Placebo	Part 2, DB period: Venglustat 15 mg
Number of subjects analysed	94	82
Units: units on a scale
least squares mean (standard error)	0.32 ( 1.27 )	-0.65 ( 1.35 )

Part 2 DB period: Venglustat 15mg versus Placebo

Statistical analysis description

LS mean, SE and P-value were estimated from MMRM analysis which included fixed categorical effects of treatment group, randomisation 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.

Comparison groups

Part 2, DB period: Venglustat 15 mg v Part 2, DB period: Placebo

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5996 ^[26]

Method

MMRM

Parameter type

LS mean difference

Point estimate

-0.97

Confidence interval

level

95%

sides

2-sided

lower limit

-4.63

upper limit

2.68

Variability estimate

Standard error of the mean

Dispersion value

1.85

Notes
[26] - The threshold for statistical significance was 0.05.

Secondary: 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

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End point 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 ^[27]

End point description

MDS-UPDRS:multimodal scale consists of 4 parts. Part I assessed non-motor experiences of daily living and has 2 components (total score:0to52): Part IA had 6 questions and was assessed by examiner (total score:0to24). Part IB had 7 questions on non-motor experiences of daily living which was completed by subject (total score:0to28). Part II (13 questions completed by subject) assessed motor experiences of daily living (total score:0to52). Part III assessed motor signs of PD and was administered by rater (total score:0to132). Part III had 33 scores based on 18 items. In all parts, higher score=more symptoms. For each question, numeric score range was 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. ITT population. Number of subjects analysed=subjects evaluable. This endpoint was not planned to be collected and analysed for Part 1, Part 2 DB period re-randomised and LTFU.

End point type

Secondary

End point timeframe

Baseline to Week 52

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	Part 2, DB period: Placebo	Part 2, DB period: Venglustat 15 mg
Number of subjects analysed	95	81
Units: units on a scale
least squares mean (standard error)	5.87 ( 1.45 )	9.99 ( 1.55 )

Part 2 DB period: Venglustat 15mg versus Placebo

Statistical analysis description

Comparison groups

Part 2, DB period: Venglustat 15 mg v Part 2, DB period: Placebo

Number of subjects included in analysis

176

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0535 ^[28]

Method

MMRM

Parameter type

LS mean difference

Point estimate

4.13

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

8.32

Variability estimate

Standard error of the mean

Dispersion value

2.13

Notes
[28] - The threshold for statistical significance was 0.05.

Secondary: Part 2: Change From Baseline to Week 52 in Hoehn and Yahr (H and Y) Score

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End point title

Part 2: Change From Baseline to Week 52 in Hoehn and Yahr (H and Y) Score ^[29]

End point 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. Analysis was performed on ITT population. Here, number of subjects analysed = subjects evaluable for this endpoint. Data for this endpoint was not planned to be collected and analysed for Part 1, Part 2 DB period re-randomised subjects and Part 2 LTFU period, as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Baseline to Week 52

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was reported for all applicable arms in the study.

End point values	Part 2, DB period: Placebo	Part 2, DB period: Venglustat 15 mg
Number of subjects analysed	95	80
Units: units on a scale
least squares mean (standard error)	0.18 ( 0.05 )	0.20 ( 0.06 )

Part 2 DB period: Venglustat 15mg versus Placebo

Statistical analysis description

LS mean, SE and P-value: estimated from MMRM analysis which included fixed categorical effects of treatment group, randomisation 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.

Comparison groups

Part 2, DB period: Venglustat 15 mg v Part 2, DB period: Placebo

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.74 ^[30]

Method

MMRM

Parameter type

LS mean difference

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.17

Variability estimate

Standard error of the mean

Dispersion value

0.08

Notes
[30] - The threshold for statistical significance was 0.05.

Adverse events

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Timeframe for reporting adverse events

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 subjects; in Part 2 DB period: up to 60 weeks; in Part 2 LTFU period: up to 164 weeks)

Adverse event reporting additional 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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Part 1: Placebo (ROW)

Reporting group description

Subjects 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.

Reporting group title

Part 1: Venglustat 4 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 4 milligrams (mg) capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Venglustat 8 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 8 mg capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Venglustat 15 mg (ROW)

Reporting group description

Subjects from ROW (except Japan), received venglustat 15 mg capsule orally QD for up to 36 weeks in Part 1.

Reporting group title

Part 1: Placebo (Japan only)

Reporting group description

Japanese subjects received placebo (matched to venglustat) capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 4 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 4 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 8 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 8 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 1: Venglustat 15 mg (Japan only)

Reporting group description

Japanese subjects received venglustat 15 mg capsule orally QD for up to 52 weeks in Part 1.

Reporting group title

Part 2, DB period: Placebo

Reporting group description

Subjects received placebo (matched to venglustat) capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, DB period: Venglustat 15 mg

Reporting group description

Subjects received venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, DB period: Placebo (Re-randomised from Part 1)

Reporting group description

Reporting group title

Part 2,DB period:Venglustat 15 mg (Re-randomised from Part 1)

Reporting group description

Subjects 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-randomised to receive venglustat 15 mg capsule orally QD for 52 weeks in Part 2 DB period.

Reporting group title

Part 2, LTFU period: Placebo then Venglustat 15 mg

Reporting group description

Reporting group title

Part 2, LTFU period: Venglustat 15 mg

Reporting group description

Subjects 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.

Reporting group title

Part 2,LTFU:Placebo then Veng 15mg (Re-randomised from Part 1)

Reporting group description

Reporting group title

Part 2, LTFU: Venglustat 15 mg (Re-randomised from Part 1)

Reporting group description

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-randomised from Part 1)

Part 2,DB period:Venglustat 15 mg (Re-randomised 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 15mg (Re-randomised from Part 1)

Part 2, LTFU: Venglustat 15 mg (Re-randomised from Part 1)

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (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%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Basal Cell Carcinoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Breast Cancer Female

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant Melanoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant Melanoma In Situ

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-Small Cell Lung Cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ovarian Epithelial Cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Prostate Cancer

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Anastomotic Leak

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fall

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Femoral Neck Fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intentional Overdose

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Post Lumbar Puncture Syndrome

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

2 / 111 (1.80%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Postoperative Delirium

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Radius Fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rib Fracture

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin Laceration

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural Haematoma

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep Vein Thrombosis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertension

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertensive Urgency

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Orthostatic Hypotension

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (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%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial Fibrillation

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Arrest

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cardio-Respiratory Arrest

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Nervous system disorders

Cerebellar Haemorrhage

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cognitive Disorder

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

1 / 10 (10.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Freezing Phenomenon

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lumbar Radiculopathy

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

On And Off Phenomenon

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parkinson's Disease

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

3 / 87 (3.45%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 4

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Posterior Reversible Encephalopathy Syndrome

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

3 / 110 (2.73%)

0 / 10 (0.00%)

0 / 13 (0.00%)

2 / 87 (2.30%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

2 / 4

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Transient Ischaemic Attack

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal Pain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Impaired Gastric Emptying

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Inguinal Hernia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal Obstruction

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Volvulus

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Hypoxia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary Embolism

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional State

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

1 / 10 (10.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hallucination

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychotic Disorder

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Suicide Attempt

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute Kidney Injury

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (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%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Micturition Urgency

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ureterolithiasis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back Pain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Muscle Rigidity

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal Pain

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal Abscess

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Covid-19

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

1 / 10 (10.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colonic Abscess

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

1 / 110 (0.91%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteomyelitis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subacute Endocarditis

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 111 (0.90%)

0 / 110 (0.00%)

0 / 10 (0.00%)

0 / 13 (0.00%)

0 / 87 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary Tract Infection

alternative dictionary used: MedDRA 24.0

subjects affected / exposed

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 111 (0.00%)

0 / 110 (0.00%)

0 / 10 (0.00%)

1 / 13 (7.69%)

1 / 87 (1.15%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-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-randomised from Part 1)	Part 2,DB period:Venglustat 15 mg (Re-randomised 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 15mg (Re-randomised from Part 1)	Part 2, LTFU: Venglustat 15 mg (Re-randomised from Part 1)
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	4 / 4 (100.00%)	4 / 5 (80.00%)	4 / 4 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)	2 / 3 (66.67%)	87 / 111 (78.38%)	95 / 110 (86.36%)	8 / 10 (80.00%)	11 / 13 (84.62%)	53 / 87 (60.92%)	39 / 75 (52.00%)	7 / 10 (70.00%)	8 / 11 (72.73%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vascular disorders
Hypertension
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 111 (3.60%)	3 / 110 (2.73%)	0 / 10 (0.00%)	1 / 13 (7.69%)	3 / 87 (3.45%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	5	3	0	1	3	0	1	0
Orthostatic Hypotension
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	3 / 111 (2.70%)	3 / 110 (2.73%)	0 / 10 (0.00%)	1 / 13 (7.69%)	2 / 87 (2.30%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	3	0	1	2	0	0	0
General disorders and administration site conditions
Fatigue
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 111 (3.60%)	12 / 110 (10.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	3 / 87 (3.45%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	4	13	0	1	3	1	0	0
Oedema Peripheral
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	7 / 111 (6.31%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	8	1	0	0	1	2	0	0
Pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	3 / 111 (2.70%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	1	0	1	0	0	0	0
Reproductive system and breast disorders
Ovarian Failure
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Uterine Haemorrhage
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	10 / 110 (9.09%)	0 / 10 (0.00%)	1 / 13 (7.69%)	2 / 87 (2.30%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	1	11	0	1	3	0	0	1
Dyspnoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	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%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	1	1	0	0
Oropharyngeal Pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1
Sleep Apnoea Syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	1	0	0	0	0	0
Tonsillar Cyst
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Psychiatric disorders
Anxiety
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	5 / 110 (4.55%)	0 / 10 (0.00%)	2 / 13 (15.38%)	7 / 87 (8.05%)	2 / 75 (2.67%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	6	5	0	2	7	3	1	0
Confusional State
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 111 (1.80%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	1	0	1	0	0	0	0
Delirium
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Depressed Mood
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 111 (1.80%)	6 / 110 (5.45%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	2	8	0	0	1	0	0	0
Depression
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	9 / 110 (8.18%)	1 / 10 (10.00%)	0 / 13 (0.00%)	6 / 87 (6.90%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	9	10	1	0	6	3	0	0
Drug Abuse
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hallucination
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 111 (2.70%)	3 / 110 (2.73%)	0 / 10 (0.00%)	0 / 13 (0.00%)	2 / 87 (2.30%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	3	3	0	0	2	2	0	0
Hallucination, Visual
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	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%)	1 / 13 (7.69%)	1 / 87 (1.15%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	1	0	1	1	1	1	0
Impulsive Behaviour
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	1	0	1	0	0	0	0
Insomnia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	9 / 110 (8.18%)	0 / 10 (0.00%)	0 / 13 (0.00%)	5 / 87 (5.75%)	3 / 75 (4.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	6	10	0	0	6	3	1	0
Panic Attack
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	3 / 110 (2.73%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	3	0	0	0	1	0	0
Poor Quality Sleep
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	1 / 87 (1.15%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	2	1	0	1	1	1	0	0
Rapid Eye Movement Sleep Behaviour Disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Investigations
Alanine Aminotransferase Increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	1 / 110 (0.91%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1	0	0	1	0	0
Blood Creatine Phosphokinase Increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	1	0	1	0	0
Cardiac Murmur
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	1	0	0	0	0	0	0
Hepatic Enzyme Increased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Weight Decreased
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	3 / 111 (2.70%)	2 / 110 (1.82%)	0 / 10 (0.00%)	1 / 13 (7.69%)	2 / 87 (2.30%)	2 / 75 (2.67%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	3	2	0	1	2	2	0	1
Injury, poisoning and procedural complications
Arthropod Bite
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eyelid Injury
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 3 (33.33%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Fall
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	18 / 111 (16.22%)	10 / 110 (9.09%)	0 / 10 (0.00%)	1 / 13 (7.69%)	9 / 87 (10.34%)	2 / 75 (2.67%)	0 / 10 (0.00%)	3 / 11 (27.27%)
occurrences all number	0	0	0	1	0	0	0	0	24	12	0	4	12	3	0	3
Ligament Rupture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Limb Injury
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Post Lumbar Puncture Syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 111 (2.70%)	4 / 110 (3.64%)	0 / 10 (0.00%)	0 / 13 (0.00%)	2 / 87 (2.30%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	4	4	0	0	2	3	0	0
Procedural Nausea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Procedural Pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0
Procedural Vomiting
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 111 (0.00%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	1	0	0	0	0	0	0
Rib Fracture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	0
Thermal Burn
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Amnesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	1	0	0	0	0
Chorea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cognitive Disorder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	4 / 111 (3.60%)	3 / 110 (2.73%)	0 / 10 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	3	0	0	3	1	1	0
Dizziness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	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%)	10 / 111 (9.01%)	12 / 110 (10.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	6 / 87 (6.90%)	1 / 75 (1.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	10	14	0	0	6	1	0	1
Headache
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	2 / 4 (50.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	15 / 111 (13.51%)	22 / 110 (20.00%)	0 / 10 (0.00%)	3 / 13 (23.08%)	2 / 87 (2.30%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	2	0	1	0	0	1	0	0	20	31	0	3	2	3	0	0
Hyperreflexia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hypoaesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 110 (1.82%)	0 / 10 (0.00%)	1 / 13 (7.69%)	3 / 87 (3.45%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	1	3	0	0	0
Loss Of Consciousness
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Memory Impairment
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 111 (1.80%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Paraesthesia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	1	0	2	0	1	0	0
Parkinson's Disease
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	8 / 110 (7.27%)	0 / 10 (0.00%)	2 / 13 (15.38%)	11 / 87 (12.64%)	4 / 75 (5.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	1	0	0	0	0	0	7	8	0	2	11	4	0	1
Peripheral Sensory Neuropathy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Radial Nerve Palsy
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Resting Tremor
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0
Restless Legs Syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	4 / 110 (3.64%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	1 / 75 (1.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	4	0	0	1	1	0	1
Sciatica
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Sleep Deficit
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Somnolence
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	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%)	3 / 111 (2.70%)	6 / 110 (5.45%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	3 / 75 (4.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	0	0	0	0	0	0	0	3	6	0	0	0	3	0	1
Tremor
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	5 / 111 (4.50%)	8 / 110 (7.27%)	0 / 10 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	6	9	0	0	3	0	0	0
Ear and labyrinth disorders
Tinnitus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Tympanic Membrane Perforation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vertigo
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 111 (1.80%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	2	0	1	0	1	0	0	0
Eye disorders
Blepharitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	4 / 111 (3.60%)	2 / 110 (1.82%)	0 / 10 (0.00%)	1 / 13 (7.69%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	2	0	1	1	0	0	0
Borderline Glaucoma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Cataract Cortical
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	7 / 111 (6.31%)	4 / 110 (3.64%)	1 / 10 (10.00%)	1 / 13 (7.69%)	5 / 87 (5.75%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	7	5	1	2	6	4	0	0
Cataract Nuclear
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	9 / 110 (8.18%)	1 / 10 (10.00%)	1 / 13 (7.69%)	11 / 87 (12.64%)	4 / 75 (5.33%)	0 / 10 (0.00%)	2 / 11 (18.18%)
occurrences all number	0	1	0	0	0	0	0	0	7	9	1	1	11	4	0	2
Corneal Infiltrates
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Dry Eye
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	1	0	0	0	0	0	0	1	1	0	0	0	0	0	1
Eczema Eyelids
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eye Irritation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Glaucoma
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 111 (0.00%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1	0	0
Hypermetropia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Vision Blurred
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	3 / 110 (2.73%)	0 / 10 (0.00%)	1 / 13 (7.69%)	2 / 87 (2.30%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	3	0	1	2	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Abdominal Distension
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Anal Haemorrhage
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Chronic Gastritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Constipation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	8 / 111 (7.21%)	23 / 110 (20.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	3 / 87 (3.45%)	3 / 75 (4.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	8	25	0	0	3	4	1	0
Cyclic Vomiting Syndrome
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Dental Caries
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0
Diarrhoea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 111 (3.60%)	5 / 110 (4.55%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	4	5	0	0	1	1	0	0
Dry Mouth
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	7 / 110 (6.36%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	7	0	0	1	0	0	0
Dysphagia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Eructation
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0
Nausea
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	8 / 111 (7.21%)	23 / 110 (20.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	5 / 87 (5.75%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	1	1	0	0	0	3	0	0	9	27	0	1	5	0	0	1
Periodontal Disease
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vomiting
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 111 (2.70%)	9 / 110 (8.18%)	0 / 10 (0.00%)	0 / 13 (0.00%)	4 / 87 (4.60%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	3	12	0	0	4	0	0	0
Skin and subcutaneous tissue disorders
Eczema
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0
Rash
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	2 / 110 (1.82%)	1 / 10 (10.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	3	1	0	0	2	0	0
Rash Papular
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Skin Ulcer
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Urticaria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Dysuria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 110 (1.82%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1
Hypertonic Bladder
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Micturition Urgency
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 111 (1.80%)	3 / 110 (2.73%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	2	3	0	0	1	1	0	0
Nocturia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	1	0	0	0	0	0	0
Pollakiuria
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 3 (33.33%)	1 / 111 (0.90%)	1 / 110 (0.91%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	1	0	1	0	0	0	0
Urinary Incontinence
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	1	1	0
Endocrine disorders
Hypothyroidism
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	7 / 111 (6.31%)	5 / 110 (4.55%)	1 / 10 (10.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	4 / 75 (5.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	7	5	1	1	0	4	0	0
Back Pain
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	8 / 111 (7.21%)	9 / 110 (8.18%)	0 / 10 (0.00%)	2 / 13 (15.38%)	1 / 87 (1.15%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	12	14	0	2	1	2	0	0
Extremity Contracture
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Muscle Spasms
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 111 (1.80%)	2 / 110 (1.82%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	3	2	0	0	1	0	0	1
Pain In Extremity
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	8 / 111 (7.21%)	5 / 110 (4.55%)	0 / 10 (0.00%)	0 / 13 (0.00%)	2 / 87 (2.30%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	8	5	0	0	2	1	0	0
Infections and infestations
Covid-19
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	4 / 75 (5.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	4	0	0
Conjunctivitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	2 / 110 (1.82%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	2 / 75 (2.67%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	0	1	2	0	1
Empyema
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Fungal Skin Infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Gastroenteritis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1
Nasopharyngitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	11 / 111 (9.91%)	10 / 110 (9.09%)	3 / 10 (30.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	11	13	4	0	1	0	1	0
Pulpitis Dental
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 111 (0.90%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0
Retinitis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	0 / 110 (0.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Tinea Pedis
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	0 / 110 (0.00%)	0 / 10 (0.00%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Upper Respiratory Tract Infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 111 (0.00%)	2 / 110 (1.82%)	2 / 10 (20.00%)	0 / 13 (0.00%)	1 / 87 (1.15%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	4	2	0	1	0	1	0
Urinary Tract Infection
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 111 (5.41%)	11 / 110 (10.00%)	0 / 10 (0.00%)	0 / 13 (0.00%)	2 / 87 (2.30%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	6	17	0	0	2	3	0	0
Metabolism and nutrition disorders
Decreased Appetite
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	6 / 110 (5.45%)	0 / 10 (0.00%)	0 / 13 (0.00%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	7	0	0	0	0	0	0
Type 2 Diabetes Mellitus
alternative dictionary used: MedDRA 24.0
subjects affected / exposed	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%)	1 / 13 (7.69%)	0 / 87 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

08 Dec 2016

The following changes were made: - Updated inclusion and exclusion criteria. - In Part 2 Treatment Phase, site Visit 4 at Week 0, Day 3 had been removed from Part 2: Study schedule of assessments (Periods 1 and 2) flowchart for consistency (it was added to original protocol in error). Therefore, visit numbers throughout the protocol had been renumbered.

06 Jun 2017

The following changes were made: - Updated inclusion and exclusion criteria: 'Increase the subject upper age limit from 70 to 80 years old'. - Revised exclusion criteria to specify the prohibited duration of medication use and deleted the words 'of screening'. - Clarified that the internal review committee can comprise individuals involved in the conduct of the study. - Updated table of contents, flow charts, sections, table footnotes and citations and renumbered references. - Tables were reformatted. - Abbreviations were updated in text and table footnotes. - References were updated.

03 Sep 2020

The following changes were made: - Added the supplementary visits and corresponding assessments related to the 1-year prolongation of the long-term follow-up period (Period 3). - Clarified the objectives of the long-term follow-up period (period 3). - Specified that Visit 15 (Week 208) would be the last study visit for subjects who would be transitioned to a long-term study with GZ/SAR402671. - Clarified the PD medications allowed during the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

This study did not achieve its primary or secondary endpoints at the time of the analysis of the double-blind 52-week treatment period of Part 2 and was terminated early.

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Clinical trials

Clinical Trial Results: Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients with Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

Primary: Part 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

Primary: Part 1: Number of Subjects With Abnormal Physical Examination Findings

Primary: Part 1: Number of Subjects With Abnormal Physical Examination Findings

Primary: Part 1: Number of Subjects With Abnormal Neurological Examination Findings

Primary: Part 1: Number of Subjects With Abnormal Neurological Examination Findings

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Hematology

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Hematology

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Renal Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Parameters

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Vital Signs Abnormalities

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Ophthalmological Abnormalities

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Ophthalmological Abnormalities

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Electrocardiogram Abnormalities

Primary: Part 1: Number of Subjects With Potentially Clinically Significant Electrocardiogram Abnormalities

Primary: 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

Primary: 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

Secondary: Part 2: Change From Baseline to Week 52 in Parkinson's Disease Cognitive Rating Scale (PD-CRS) Total score

Secondary: Part 2: Change From Baseline to Week 52 in Parkinson's Disease Cognitive Rating Scale (PD-CRS) Total score

Secondary: 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

Secondary: 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

Secondary: Part 2: Change From Baseline to Week 52 in Hoehn and Yahr (H and Y) Score

Secondary: Part 2: Change From Baseline to Week 52 in Hoehn and Yahr (H and Y) Score

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of GZ/SAR402671 in Patients with Early-stage Parkinson's Disease Carrying a GBA Mutation or Other Pre-specified Variant.