Trial Outcomes & Findings for A Study to Evaluate the Efficacy, Safety, and Tolerability of SAGE-324 in Participants With Essential Tremor (NCT NCT04305275)

Last Updated: 2024-04-17

Results Overview

The Essential Tremor Rating Assessment Scale (TETRAS) is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. Mixed model repeated measures (MMRM) was used for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

69 participants

Primary outcome timeframe

Baseline, Day 29

Results posted on

2024-04-17

Participant Flow

Participants were enrolled at 27 active investigative sites in the United States from 19 May 2020 to 15 February 2021.

A total of 153 participants were screened, of which 69 participants were randomized to receive SAGE-324 or placebo.

Participant milestones

Participant milestones
Measure	SAGE-324 60 mg Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days.	SAGE-324 Matched Placebo Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.
Overall Study STARTED	34	35
Overall Study Safety Set	34	35
Overall Study Full Analysis Set	33	34
Overall Study COMPLETED	21	33
Overall Study NOT COMPLETED	13	2

Reasons for withdrawal

Reasons for withdrawal
Measure	SAGE-324 60 mg Participants received SAGE-324, 60 milligrams (mg), oral tablets, once daily (QD), in the morning for 28 days.	SAGE-324 Matched Placebo Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.
Overall Study Adverse Event	4	0
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Participant	8	1

Baseline Characteristics

Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SAGE-324 60 mg n=34 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.	SAGE-324 Matched Placebo n=35 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	Total n=69 Participants Total of all reporting groups
Age, Continuous	69.4 years STANDARD_DEVIATION 6.91 • n=34 Participants	64.7 years STANDARD_DEVIATION 13.18 • n=35 Participants	67.0 years STANDARD_DEVIATION 10.75 • n=69 Participants
Sex: Female, Male Female	12 Participants n=34 Participants	20 Participants n=35 Participants	32 Participants n=69 Participants
Sex: Female, Male Male	22 Participants n=34 Participants	15 Participants n=35 Participants	37 Participants n=69 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=34 Participants	4 Participants n=35 Participants	7 Participants n=69 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=34 Participants	29 Participants n=35 Participants	60 Participants n=69 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=34 Participants	2 Participants n=35 Participants	2 Participants n=69 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=34 Participants	0 Participants n=35 Participants	0 Participants n=69 Participants
Race (NIH/OMB) Asian	0 Participants n=34 Participants	1 Participants n=35 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=34 Participants	1 Participants n=35 Participants	1 Participants n=69 Participants
Race (NIH/OMB) Black or African American	2 Participants n=34 Participants	1 Participants n=35 Participants	3 Participants n=69 Participants
Race (NIH/OMB) White	32 Participants n=34 Participants	32 Participants n=35 Participants	64 Participants n=69 Participants
Race (NIH/OMB) More than one race	0 Participants n=34 Participants	0 Participants n=35 Participants	0 Participants n=69 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=34 Participants	0 Participants n=35 Participants	0 Participants n=69 Participants
Region of Enrollment United States	34 participants n=34 Participants	35 participants n=35 Participants	69 participants n=69 Participants
Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 Upper Limb Tremor Score	12.82 score on a scale STANDARD_DEVIATION 1.727 • n=33 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	12.28 score on a scale STANDARD_DEVIATION 1.698 • n=34 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	12.54 score on a scale STANDARD_DEVIATION 1.720 • n=67 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.
Kinesia ONE™ Accelerometer Score	10.66 score on a scale STANDARD_DEVIATION 3.825 • n=33 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed" signifies the number of participants with data available at the Baseline for the analysis of the specified parameter.	8.80 score on a scale STANDARD_DEVIATION 3.762 • n=33 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed" signifies the number of participants with data available at the Baseline for the analysis of the specified parameter.	9.73 score on a scale STANDARD_DEVIATION 3.879 • n=66 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Number analyzed" signifies the number of participants with data available at the Baseline for the analysis of the specified parameter.
TETRAS Activities of Daily Living (ADL) Score	26.33 score on a scale STANDARD_DEVIATION 8.502 • n=33 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	26.74 score on a scale STANDARD_DEVIATION 6.837 • n=34 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	26.54 score on a scale STANDARD_DEVIATION 7.646 • n=67 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.
TETRAS Total Performance Subscale Score	27.68 score on a scale STANDARD_DEVIATION 4.618 • n=33 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	27.09 score on a scale STANDARD_DEVIATION 5.157 • n=34 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.	27.38 score on a scale STANDARD_DEVIATION 4.871 • n=67 Participants • Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment.

PRIMARY outcome

Timeframe: Baseline, Day 29

Population: Full Analysis Set included all randomized participants who received any amount of SAGE-324 or placebo and had a baseline and at least one postbaseline efficacy assessment. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=33 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=21 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score on Day 29	-1.24 score on a scale Standard Error 0.349	-2.31 score on a scale Standard Error 0.401

SECONDARY outcome

Timeframe: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, and 42

TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. The TETRAS performance subscale upper limb tremor total score is the sum of the TETRAS individual item scores from both arms of the body. The TETRAS individual item score included TETRAS Performance Subscale items 4a, 4b, and 4c scores \[4a: limbs extended forward maneuver, 4b: wing-beating (elbows flexed) maneuver, and 4c: kinetic (finger-nose-finger) maneuver\] scores from both arms of the body. Each individual item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of the body. The total upper limb score combined for both arms ranges from 0 to 24. Higher scores=more severe tremor. A negative change from baseline =improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=34 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=33 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 8	-0.86 score on a scale Standard Error 0.273	-1.67 score on a scale Standard Error 0.287
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 15, Pre-dose	-1.31 score on a scale Standard Error 0.312	-1.78 score on a scale Standard Error 0.344
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 15, 5 Hours Post-dose	-2.24 score on a scale Standard Error 0.400	-2.64 score on a scale Standard Error 0.452
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 15, 8 Hours Post-dose	-2.09 score on a scale Standard Error 0.389	-2.36 score on a scale Standard Error 0.441
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 22	-1.33 score on a scale Standard Error 0.318	-2.10 score on a scale Standard Error 0.360
Change From Baseline Compared to Placebo in TETRAS Performance Subscale Part 4 Upper Limb Tremor Score at Days 8, 15, 22, and 42 Change From Baseline at Day 42	-1.85 score on a scale Standard Error 0.378	-1.23 score on a scale Standard Error 0.407

SECONDARY outcome

Timeframe: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42

Kinesia ONE™ measures three-dimensional motion converted to scores. Motion in both arms were captured. The accelerometer-based Kinesia ONE individual scores is the sum of the individual item scores across both arms of the body. The individual items included forward outstretched postural tremor, lateral "wing beating" postural tremor, and kinetic tremor scores from both arms of the body. Each individual item score ranges from 0 (no tremor) to 4 (severe tremor); with 0 to 12 being the score range for each arm of the body. The Kinesia ONE total score combined for both arms ranges from 0 to 24. Higher scores=more tremors/greater tremor amplitude. A negative change from baseline indicates improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=33 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=33 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 8	-0.90 score on a scale Standard Error 0.451	-1.00 score on a scale Standard Error 0.470
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, Pre-dose	-1.37 score on a scale Standard Error 0.462	-0.44 score on a scale Standard Error 0.499
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, 5 Hours Post-dose	-1.45 score on a scale Standard Error 0.551	-1.94 score on a scale Standard Error 0.613
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, 8 Hours Post-dose	-1.39 score on a scale Standard Error 0.532	-0.85 score on a scale Standard Error 0.585
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 22	-0.83 score on a scale Standard Error 0.491	-0.50 score on a scale Standard Error 0.540
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 29	-1.12 score on a scale Standard Error 0.497	-0.48 score on a scale Standard Error 0.562
Change From Baseline Compared to Placebo in Kinesia ONE™ Accelerometer Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 42	-1.44 score on a scale Standard Error 0.534	-0.78 score on a scale Standard Error 0.557

SECONDARY outcome

Timeframe: Baseline, Days 8, 15, 22, 29, and 42

The ADL subscale assesses how ET impacts typical activities of daily living (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, and activities affected by UL tremor. It consists of 12 items, each rated from 0 (normal activity) to 4 (severe abnormality). The overall ADL score, calculated as the sum of subscale items ranges from 0 to 48. Higher scores indicate greater tremor severity, while a negative change from baseline indicates improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=34 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=33 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 8	-2.54 score on a scale Standard Error 0.805	-5.34 score on a scale Standard Error 0.845
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15	-2.47 score on a scale Standard Error 0.859	-5.43 score on a scale Standard Error 0.945
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 22	-2.68 score on a scale Standard Error 0.802	-5.24 score on a scale Standard Error 0.904
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 29	-2.87 score on a scale Standard Error 0.780	-4.24 score on a scale Standard Error 0.940
Change From Baseline Compared to Placebo in TETRAS ADL Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 42	-3.27 score on a scale Standard Error 0.837	-2.14 score on a scale Standard Error 0.905

SECONDARY outcome

Timeframe: Baseline, Days 8, 15 (pre-dose, 5, and 8 hours post-dose), 22, 29, and 42

The total performance score is based on the overall rating of tremor amplitude in the voice, limbs, head, face, and trunk while performing pre-specified tasks, and functional task capabilities (handwriting, spiral drawing, and holding a pen over a dot). Each of these items is rated from 0 (no tremor) to 4 (severe tremor) with an overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicate greater tremor severity. A negative change from baseline indicates improvement. MMRM was used for the analysis.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=34 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=33 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 8	-2.30 score on a scale Standard Error 0.743	-3.55 score on a scale Standard Error 0.780
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, Pre-dose	-2.55 score on a scale Standard Error 0.805	-3.46 score on a scale Standard Error 0.878
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, 5 Hours Post-dose	-4.38 score on a scale Standard Error 0.892	-5.90 score on a scale Standard Error 1.015
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 15, 8 Hours Post-dose	-4.61 score on a scale Standard Error 0.855	-4.61 score on a scale Standard Error 0.954
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 22	-2.92 score on a scale Standard Error 0.811	-3.16 score on a scale Standard Error 0.914
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 29	-2.90 score on a scale Standard Error 0.817	-3.22 score on a scale Standard Error 0.922
Change From Baseline Compared to Placebo in TETRAS Total Performance Score at Days 8, 15, 22, 29, and 42 Change From Baseline at Day 42	-3.87 score on a scale Standard Error 0.761	-1.59 score on a scale Standard Error 0.820

SECONDARY outcome

Timeframe: From the first dose of the study drug up to the end of the study (i.e., up to approximately 42 days)

Population: Safety Set included all participants who were administered SAGE-324 or placebo.

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. A TEAE was defined as an AE with onset after the start of investigational product (IP), or any worsening of a preexisting medical condition/AE with onset after the start of IP and throughout the study.

Outcome measures

Outcome measures
Measure	SAGE-324 Matched Placebo n=35 Participants Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.	SAGE-324 60 mg n=34 Participants Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	20 Participants	33 Participants

Adverse Events

SAGE-324 60 mg

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

SAGE-324 Matched Placebo

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	SAGE-324 60 mg n=34 participants at risk Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.	SAGE-324 Matched Placebo n=35 participants at risk Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.
Psychiatric disorders Mental status changes	5.9% 2/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Metabolism and nutrition disorders Dehydration	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Headache	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Transient ischaemic attack	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Cardiac disorders Angina pectoris	0.00% 0/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	2.9% 1/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	2.9% 1/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.

Other adverse events

Additional Information

Medical Monitor

Sage Therapeutics

Phone: (617) 299-8380

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).
Publication restrictions are in place

Restriction type: OTHER

Measure	SAGE-324 60 mg n=34 participants at risk Participants received SAGE-324, 60 mg, oral tablets, QD, in the morning for 28 days.	SAGE-324 Matched Placebo n=35 participants at risk Participants received SAGE-324 matched placebo, oral tablets, QD, in the morning for 28 days.
Nervous system disorders Somnolence	67.6% 23/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Dizziness	38.2% 13/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	11.4% 4/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
General disorders Fatigue	14.7% 5/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	11.4% 4/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Balance disorder	14.7% 5/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Eye disorders Diplopia	11.8% 4/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Dysarthria	11.8% 4/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
General disorders Gait disturbance	11.8% 4/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Disturbance in attention	8.8% 3/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	8.6% 3/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Myoclonus	8.8% 3/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Gastrointestinal disorders Diarrhoea	5.9% 2/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	8.6% 3/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Paraesthesia	5.9% 2/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Lethargy	5.9% 2/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Speech disorder	5.9% 2/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	0.00% 0/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Headache	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	17.1% 6/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Nervous system disorders Coordination abnormal	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	8.6% 3/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
General disorders Asthenia	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Psychiatric disorders Insomnia	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Infections and infestations Urinary tract infection	2.9% 1/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Psychiatric disorders Irritability	0.00% 0/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/34 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.	5.7% 2/35 • From the first dose of the study drug up to the end of the study (i.e. up to approximately 42 days) Safety Set included all participants who were administered the study drug.