Study to Evaluate SAGE-324 in Participants With Essential... | NCT05173012

Status Module

Name	Class
Biogen	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
SAGE-324 Matched Placebo	Placebo Comparator	Participants will receive SAGE-324 matched placebo, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324 matched placebo, oral tablets, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324 matched placebo, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 milligrams (mg) of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.	Drug: SAGE-324 Matched Placebo
SAGE-324 15 mg	Experimental	Participants will receive SAGE-324, 15 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.	Drug: SAGE-324
SAGE-324 30 mg	Experimental	Participants will receive SAGE-324, 30 mg, stratified by baseline propranolol use. Monotherapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period. Adjunct therapy: Participants will receive SAGE-324, 30 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to Screening up to Day 90 in a double-blind treatment period.	Drug: SAGE-324
SAGE-324 60 mg

Name	Type	Description	Arm Group Labels	Other Names
SAGE-324	Drug	SAGE-324 oral tablets.	SAGE-324 15 mg SAGE-324 30 mg SAGE-324 60 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort	TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. For the TETRAS Performance Subscale Item 4 (upper limb), three maneuvers/assessments were to be completed for both arms, first for the right arm and then for the left, specifically Item 4a, limbs extended forward maneuver (postural tremor), Item 4b, wing-beating [elbows flexed] maneuver (postural tremor), and Item 4c finger-nose-finger maneuver (kinetic tremor). Each assessment is rated on a 0 to 4 scale of severity in 0.5-point increments, with higher scores indicating more severe tremor. The Performance Subscale Item 4 (upper limb) total score range for a given side (left or right) is 0 to 12, and for both sides combined is 0 to 24. A negative change from baseline indicates improvement. Mixed model for repeated measures (MMRM) was used for the analysis.	Baseline, Day 91

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort	TETRAS ADL Subscale (items 1-12) assesses how ET affects typical ADL (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, activities affected by UL tremor). TETRAS ADL composite score comprises Items 1-11 of ADL Subscale (Item 1: speech impairment; Item 10: occupational impairment; remaining 9 items: impairment in activities affected by UL tremor) and Item 6 of Performance Subscale (spiral drawing). Each of individual item is rated on a scale from 0 (normal activity) to 4 (severe abnormality); responses of 0 & 1 in TETRAS ADL Subscale Items 1 to 11 were collapsed such that scale is 0 (normal/slightly abnormal), 1 (mildly abnormal), 2 (moderately abnormal), and 3 (severely abnormal). Performance Subscale Item 6 responses were collapsed with responses having 0.5 point increments grouped with next higher integer response. ADL composite score range is 0 to 39. Higher score=greater abnormality, negative change=improvement.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of ET, as defined by all of the following criteria:
- Isolated tremor syndrome consisting of bilateral upper limb action tremor
- At least 3 years duration
- With or without tremor in other locations (eg, head, voice, or lower limbs)
Absence of other neurological signs, such as dystonia, ataxia, or parkinsonism, isolated focal tremors (eg, voice, head), task- and position-specific tremors, sudden tremor onset, or evidence of stepwise deterioration of tremor.
Participant has the following:
- Scores of at least 12 in the combined TETRAS Performance Subscale Item 4 (upper limb tremor) at both Screening and pre-dose on Day 1
- Scores of at least 6 in the total TETRAS Performance Subscale Item 4 score for the dominant upper limb (the sum of the three items for either the right or left upper limb, whichever is dominant) at both Screening and pre-dose on Day 1
Participant has a baseline TETRAS ADL Subscale score of at least 20 at Screening.
Willing to discontinue medications taken for the treatment of ET except propranolol at least 14 days or 5 half-lives (whichever is longer) prior to receiving the investigational product (IP). Medications taken for the treatment of ET that were discontinued prior to receiving IP may be resumed following Day 97. Participants in the adjunct therapy cohort must be on a stable dose of propranolol (maximum total daily propranolol dose up to 320 mg allowed) for the treatment of ET from 3 months prior to Screening through Day 97 of the study.
Participant is willing to limit use of alcohol to 2 units per day for males and 1 unit per day for females starting at least 1 week prior to Day 1 and through Day 97 of the study.
Participant is willing to maintain prestudy consumption of products that contain nicotine starting at least 1 week prior to Day 1 and through Day 97 of the study.

Exclusion Criteria:

Presence of known causes of enhanced physiological tremor.
Participant has had newly administered tremorgenic drugs (14 days or 5 half-lives [whichever is longer] prior to Day 1) or presence of alcohol withdrawal state.
Direct or indirect injury or trauma to the nervous system within 3 months before the onset of tremor.
Previous procedure for the treatment of ET, deep brain stimulation, brain lesioning, or magnetic resonance (MR) guided procedure, eg, MR-guided focused ultrasound. Use of Cala Trio bracelet for the treatment of ET from two weeks prior to Day 1 through Day 97 is prohibited.
Participant has had botulinum toxin for treatment of ET within 6 months of Screening.
Historical or clinical evidence of tremor with functional neurological syndrome origin.
Participant currently requires propranolol treatment for a medical condition other than ET.
Participant has history of substance abuse or dependence prior to Screening, has a positive screen for drugs of abuse at Screening or predose on Day 1. Participants with nicotine use disorder that impacts their tremor are excluded.

Facility	Status	City	State	ZIP	Country	Contacts
Sage Investigational Site		Hoover	Alabama	35244	United States
Sage Investigational Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Monotherapy: Placebo	Participants received SAGE-324 matched placebo, orally, once daily (QD), in the evening, from Day 1 to Day 90 in a double-blind treatment period.
FG001	Monotherapy: SAGE-324 15 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 8, 2023	May 1, 2025

Arm/Group Information

ID	Title	Description
BG000	Monotherapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
BG001	Monotherapy: SAGE-324 15 mg	Participants received SAGE-324 15 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
BG002	Monotherapy: SAGE-324 30 mg	Participants received SAGE-324 30 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
BG003	Monotherapy: SAGE-324 60 mg	Participants received SAGE-324 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
BG004	Adjunct Therapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.
BG005	Adjunct Therapy: SAGE-324 15 mg	Participants received SAGE-324 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.
BG006	Adjunct Therapy: SAGE-324 30 mg	Participants received SAGE-324, 30 mg orally, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.
BG007	Adjunct Therapy: SAGE-324 60 mg	Participants received SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG00031 ParticipantsBG00132 ParticipantsBG00232 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00031 ParticipantsBG00132 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00031 ParticipantsBG00132 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00031 ParticipantsBG00132 ParticipantsBG002

The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Score

TETRAS is clinical evaluation of essential tremor. For the TETRAS Performance Subscale Item 4 (upper limb), three maneuvers/assessments were to be completed for both arms, first for right arm and then for left, specifically Item 4a, limbs extended forward maneuver (postural tremor), Item 4b, wing-beating [elbows flexed] maneuver (postural tremor), & Item 4c finger-nose-finger maneuver (kinetic tremor). Each item score ranges from 0 to 4; with 0 to 12 being the score range for each arm of body. Total upper limb score combined for both arms range from 0 to 24. Higher scores=more severe tremor.

The Full Analysis Set included all randomized participants who received any amount of IP and had a baseline and at least one post-baseline TETRAS Performance Subscale Item 4 (upper limb tremor) total score. The number analyzed indicates the number of participants with data available for analysis.

Mean

Standard Deviation

score on a scale

Title	Denominators	Categories
	ParticipantsBG00031 ParticipantsBG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in The Essential Tremor Rating Assessment Scale (TETRAS) Performance Subscale Item 4 (Upper Limb) Total Score on Day 91 in the Monotherapy Cohort

TETRAS is a clinical evaluation of essential tremor. The TETRAS performance subscale upper limb tremor score is a component of TETRAS. For the TETRAS Performance Subscale Item 4 (upper limb), three maneuvers/assessments were to be completed for both arms, first for the right arm and then for the left, specifically Item 4a, limbs extended forward maneuver (postural tremor), Item 4b, wing-beating [elbows flexed] maneuver (postural tremor), and Item 4c finger-nose-finger maneuver (kinetic tremor). Each assessment is rated on a 0 to 4 scale of severity in 0.5-point increments, with higher scores indicating more severe tremor. The Performance Subscale Item 4 (upper limb) total score range for a given side (left or right) is 0 to 12, and for both sides combined is 0 to 24. A negative change from baseline indicates improvement. Mixed model for repeated measures (MMRM) was used for the analysis.

The Full Analysis Set included all randomized participants who received any amount of IP and had a baseline and at least one post-baseline TETRAS Performance Subscale Item 4 (upper limb tremor) total score. The overall number of participants analyzed indicates the number of participants with data available for outcome measure analysis.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Day 91

ID	Title	Description
OG000	Monotherapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
OG001	Monotherapy: SAGE-324 15 mg	Participants received SAGE-324 15 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
OG002	Monotherapy: SAGE-324 30 mg	Participants received SAGE-324 30 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.
OG003	Monotherapy: SAGE-324 60 mg	Participants received SAGE-324 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.

Units	Counts
Participants	OG00028 OG00128 OG00227 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-2.53± 0.445 OG001-2.14± 0.436 OG002-2.81± 0.449 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM	MMRM model included treatment, baseline score, assessment timepoint, and timepoint-by-treatment as explanatory variables, treated as fixed effects.	0.5325		Least Squares (LS) Mean Difference	0.39	Standard Error of the Mean	0.623	2-Sided	95	-0.84	1.62			Difference was calculated as Monotherapy: SAGE-324 15 mg - placebo.		Superiority

Secondary

Change From Baseline in TETRAS Activities of Daily Living (ADL) Composite Score in the Monotherapy Cohort

TETRAS ADL Subscale (items 1-12) assesses how ET affects typical ADL (speech, eating, drinking, dressing, personal hygiene, writing, occupational impairment, social impact, activities affected by UL tremor). TETRAS ADL composite score comprises Items 1-11 of ADL Subscale (Item 1: speech impairment; Item 10: occupational impairment; remaining 9 items: impairment in activities affected by UL tremor) and Item 6 of Performance Subscale (spiral drawing). Each of individual item is rated on a scale from 0 (normal activity) to 4 (severe abnormality); responses of 0 & 1 in TETRAS ADL Subscale Items 1 to 11 were collapsed such that scale is 0 (normal/slightly abnormal), 1 (mildly abnormal), 2 (moderately abnormal), and 3 (severely abnormal). Performance Subscale Item 6 responses were collapsed with responses having 0.5 point increments grouped with next higher integer response. ADL composite score range is 0 to 39. Higher score=greater abnormality, negative change=improvement.

The Full Analysis Set included all randomized participants who received any amount of IP and had a baseline and at least one post-baseline TETRAS Performance Subscale Item 4 (upper limb tremor) total score. The overall number of participants analyzed indicates the number of participants with data available for analysis at specified timepoint.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline, Day 91

ID	Title	Description
OG000	Monotherapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Monotherapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.	31	1	31	9	31
EG001	Monotherapy: SAGE-324 15 mg	Participants received SAGE-324 15 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.	32	1	32	13	32
EG002	Monotherapy: SAGE-324 30 mg	Participants received SAGE-324 30 mg, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.	32	0	32	15	32
EG003	Monotherapy: SAGE-324 60 mg	Participants received SAGE-324 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, orally, QD, in the evening, from Day 1 to Day 90 in a double-blind treatment period.	33	1	33	22	33
EG004	Adjunct Therapy: Placebo	Participants received SAGE-324 matched placebo, orally, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.	4	0	4	1	4
EG005	Adjunct Therapy: SAGE-324 15 mg	Participants received SAGE-324 15 mg, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.	4	0	4	3	4
EG006	Adjunct Therapy: SAGE-324 30 mg	Participants received SAGE-324, 30 mg orally, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.	5	1	5	3	5
EG007	Adjunct Therapy: SAGE-324 60 mg	Participants received SAGE-324, 15 mg from Day 1 to 14, followed by up-titration to 30 mg from Day 15 to 28, then to 45 mg from Day 29 to 42, and then to 60 mg from Day 43 to 90, oral tablets, QD, in the evening, from Day 1 to Day 90 along with a stable dose of up to 320 mg of propranolol from 3 months prior to screening up to Day 90 in a double-blind treatment period.	5	0	5	5	5

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Somnolence	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0015 affected32 at risk EG0028 affected32 at risk EG0038 affected33 at risk EG0040 affected4 at risk EG0050 affected4 at risk EG0060 affected5 at risk EG0071 affected5 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0025 affected32 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected32 at risk EG003
Headache	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0013 affected32 at risk EG0020 affected32 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected32 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Fatigue	General disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0013 affected32 at risk EG0023 affected32 at risk EG003
Feeling abnormal	General disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0022 affected32 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0022 affected32 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0023 affected32 at risk EG003
Abnormal dreams	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0022 affected32 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0021 affected32 at risk EG003
Depression	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0012 affected32 at risk EG0020 affected32 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0012 affected32 at risk EG0020 affected32 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0022 affected32 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Hypotension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Hypertension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0003 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Erectile dysfunction	Reproductive system and breast disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0012 affected32 at risk EG0020 affected32 at risk EG003
Aphasia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Cognitive disorder	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Slow speech	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0021 affected32 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Gait disturbance	General disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Blood urea increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Blood bilirubin unconjugated increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0002 affected31 at risk EG0010 affected32 at risk EG0021 affected32 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Platelet count decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Heart rate increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Conjunctival hyperaemia	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Apathy	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Glycosuria	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Dyspnoea	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003

ID	Term
D009069	Movement Disorders
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Staphylococcal infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected32 at risk EG0030 affected33 at risk EG0040 affected4 at risk EG0050 affected4 at risk EG0060 affected5 at risk EG0070 affected5 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0020 affected32 at risk EG003