Trial Outcomes & Findings for Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia (NCT NCT03214588)

Last Updated: 2021-06-14

Results Overview

The 9-HPT-1 is a measure of timed upper extremity (arm and hand) function and manual dexterity. The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. Each participant performs this task twice with each hand separately. Results on both tests are then averaged for an overall task completion time and the inverse transform is performed. A positive change from Baseline indicates improvement. Change from Baseline in 9-HPT-1 was analyzed using mixed model for repeated measures (MMRM) analysis of covariance (ANCOVA) with Baseline 9-HPT-1 as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline 9-HPT-1-by-visit interactions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2021-06-14

Participant Flow

Participants took part in the study at 6 investigative sites in the United States from 08 November 2017 to 27 December 2018.

Participants with a diagnosis of Friedreich Ataxia were randomized in a 2:1:2 ratio to receive TAK-831 75 mg TAK-831 300 mg or TAK-831 placebo-matching tablets twice daily.

Participant milestones

Participant milestones
Measure	Placebo TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Overall Study STARTED	27	14	26
Overall Study COMPLETED	26	13	24
Overall Study NOT COMPLETED	1	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Overall Study Adverse Event	1	0	2
Overall Study Reason Not Specified	0	1	0

Baseline Characteristics

Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.	Total n=67 Participants Total of all reporting groups
Age, Continuous	32.5 years STANDARD_DEVIATION 11.01 • n=5 Participants	31.1 years STANDARD_DEVIATION 11.28 • n=7 Participants	29.6 years STANDARD_DEVIATION 8.92 • n=5 Participants	31.1 years STANDARD_DEVIATION 10.23 • n=4 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	37 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants	66 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Body Mass Index (BMI)	24.89 kg/m^2 STANDARD_DEVIATION 4.920 • n=5 Participants	24.94 kg/m^2 STANDARD_DEVIATION 4.400 • n=7 Participants	23.02 kg/m^2 STANDARD_DEVIATION 3.862 • n=5 Participants	24.18 kg/m^2 STANDARD_DEVIATION 4.456 • n=4 Participants
Average Inverse Time to Complete 9-hole peg test (9-HPT-1) First Assessment	0.01740 1/seconds n=5 Participants	0.01660 1/seconds n=7 Participants	0.01575 1/seconds n=5 Participants	0.01680 1/seconds n=4 Participants
Average Inverse Time to Complete 9-hole peg test (9-HPT-1) Second Assessment	0.01710 1/seconds n=5 Participants	0.01605 1/seconds n=7 Participants	0.01595 1/seconds n=5 Participants	0.01660 1/seconds n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set (FAS) included all randomized participant who received at least 1 dose of the study drug for the treatment period. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Outcome measures
Measure	Placebo n=24 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=12 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=24 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)	0.00038 1/seconds Standard Error 0.000448	-0.00017 1/seconds Standard Error 0.000622	-0.00032 1/seconds Standard Error 0.000445

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7 and 12

Population: FAS included all randomized participant who received at least 1 dose of the study drug for the treatment period. Number analyzed is the number of participants with data available for analysis at the given time-point.

The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 36, with higher scores representing greater disability/dependency. A negative change from Baseline indicates improvement. Change from Baseline in FARS ADL upper limb function items were analyzed using MMRM ANCOVA with Baseline FARS ADL as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline FARS ADL-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS) Change from Baseline at Week 2	-0.25 score on a scale Standard Error 0.468	-1.12 score on a scale Standard Error 0.665	0.34 score on a scale Standard Error 0.463
Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS) Change from Baseline at Week 7	-0.33 score on a scale Standard Error 0.465	-0.15 score on a scale Standard Error 0.655	0.03 score on a scale Standard Error 0.467
Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS) Change from Baseline at Week 12	-0.61 score on a scale Standard Error 0.493	-0.37 score on a scale Standard Error 0.696	-0.24 score on a scale Standard Error 0.488

SECONDARY outcome

Timeframe: Baseline and Weeks 2 and 7

The 9-HPT-1 is a measure of timed upper extremity (arm and hand) function and manual dexterity. The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. Each participant performs this task twice with each hand separately. Results on both tests are then averaged for an overall task completion time, and the inverse transform is performed. A positive change from Baseline indicates improvement. Change from Baseline in 9-HPT-1 was analyzed using MMRM ANCOVA with Baseline 9-HPT-1 as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline 9-HPT-1-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Inverse Time to Complete the 9-HPT-1 Change from Baseline at Week 2	0.00087 1/seconds Standard Error 0.000371	0.00048 1/seconds Standard Error 0.000508	-0.00006 1/seconds Standard Error 0.000370
Change From Baseline in the Inverse Time to Complete the 9-HPT-1 Change from Baseline at Week 7	0.00040 1/seconds Standard Error 0.000462	0.00026 1/seconds Standard Error 0.000643	-0.00004 1/seconds Standard Error 0.000471

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7 and 12

The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently. A negative change from Baseline indicates improvement. Statistical analyses were available for the following subscales: cutting food-handling utensils, dressing and personal hygiene.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Walking	0.13 score on a scale Standard Deviation 0.516	-0.08 score on a scale Standard Deviation 0.557	0.02 score on a scale Standard Deviation 0.179
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Speech	0.07 score on a scale Standard Deviation 0.494	-0.15 score on a scale Standard Deviation 0.427	-0.06 score on a scale Standard Deviation 0.432
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Speech	0.06 score on a scale Standard Deviation 0.516	-0.08 score on a scale Standard Deviation 0.400	-0.15 score on a scale Standard Deviation 0.429
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Speech	0.06 score on a scale Standard Deviation 0.425	-0.17 score on a scale Standard Deviation 0.492	-0.02 score on a scale Standard Deviation 0.403
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Swallowing	0.00 score on a scale Standard Deviation 0.555	0.04 score on a scale Standard Deviation 0.320	-0.19 score on a scale Standard Deviation 0.618
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Swallowing	0.04 score on a scale Standard Deviation 0.422	0.08 score on a scale Standard Deviation 0.534	-0.06 score on a scale Standard Deviation 0.756
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Swallowing	-0.15 score on a scale Standard Deviation 0.403	0.13 score on a scale Standard Deviation 0.311	-0.27 score on a scale Standard Deviation 0.589
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Cutting-Handling Utensils	-0.13 score on a scale Standard Deviation 0.451	-0.04 score on a scale Standard Deviation 0.380	0.12 score on a scale Standard Deviation 0.535
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Cutting-Handling Utensils	-0.21 score on a scale Standard Deviation 0.619	-0.15 score on a scale Standard Deviation 0.240	0.08 score on a scale Standard Deviation 0.525
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Cutting-Handling Utensils	-0.19 score on a scale Standard Deviation 0.548	-0.08 score on a scale Standard Deviation 0.417	0.08 score on a scale Standard Deviation 0.482
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Dressing	0.00 score on a scale Standard Deviation 0.392	-0.12 score on a scale Standard Deviation 0.506	0.12 score on a scale Standard Deviation 0.516
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Dressing	0.04 score on a scale Standard Deviation 0.372	0.04 score on a scale Standard Deviation 0.380	-0.04 score on a scale Standard Deviation 0.292
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Dressing	0.02 score on a scale Standard Deviation 0.561	-0.04 score on a scale Standard Deviation 0.498	-0.10 score on a scale Standard Deviation 0.361
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Personal Hygiene	-0.02 score on a scale Standard Deviation 0.427	0.00 score on a scale Standard Deviation 0.456	0.15 score on a scale Standard Deviation 0.485
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Personal Hygiene	0.08 score on a scale Standard Deviation 0.659	0.19 score on a scale Standard Deviation 0.560	0.04 score on a scale Standard Deviation 0.530
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Personal Hygiene	0.08 score on a scale Standard Deviation 0.602	0.21 score on a scale Standard Deviation 0.656	0.06 score on a scale Standard Deviation 0.517
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Falling	0.06 score on a scale Standard Deviation 0.560	0.04 score on a scale Standard Deviation 0.660	0.02 score on a scale Standard Deviation 0.435
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Falling	-0.13 score on a scale Standard Deviation 0.481	0.54 score on a scale Standard Deviation 1.266	-0.04 score on a scale Standard Deviation 0.706
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Falling	-0.29 score on a scale Standard Deviation 0.932	0.50 score on a scale Standard Deviation 0.739	-0.33 score on a scale Standard Deviation 0.856
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Walking	-0.02 score on a scale Standard Deviation 0.470	-0.08 score on a scale Standard Deviation 0.494	0.08 score on a scale Standard Deviation 0.272
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Walking	0.00 score on a scale Standard Deviation 0.245	-0.08 score on a scale Standard Deviation 0.344	-0.06 score on a scale Standard Deviation 0.450
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Quality of Sitting Position	0.09 score on a scale Standard Deviation 0.605	-0.31 score on a scale Standard Deviation 0.663	0.10 score on a scale Standard Deviation 0.375
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Quality of Sitting Position	0.06 score on a scale Standard Deviation 0.497	-0.27 score on a scale Standard Deviation 0.753	0.00 score on a scale Standard Deviation 0.511
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12,Quality of Sitting Position	0.10 score on a scale Standard Deviation 0.589	-0.33 score on a scale Standard Deviation 0.778	0.08 score on a scale Standard Deviation 0.458
Change From Baseline in the ADL Component Individual Item Scores Change at Week 2, Bladder Function	-0.09 score on a scale Standard Deviation 0.555	-0.27 score on a scale Standard Deviation 0.439	0.13 score on a scale Standard Deviation 0.460
Change From Baseline in the ADL Component Individual Item Scores Change at Week 7, Bladder Function	-0.08 score on a scale Standard Deviation 0.643	-0.15 score on a scale Standard Deviation 0.555	0.08 score on a scale Standard Deviation 0.381
Change From Baseline in the ADL Component Individual Item Scores Change at Week 12, Bladder Function	-0.17 score on a scale Standard Deviation 0.504	-0.42 score on a scale Standard Deviation 0.557	-0.04 score on a scale Standard Deviation 0.550

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7 and 12

The mFARS-neuro neurological examination is a clinician-rated measure based on neural substrates affected in Friedreich ataxia including: bulbar on a scale of 0-11, upper limb coordination on a scale of 0-36, lower limb coordination on a scale of 0-16, and upright stability/gait functions on a scale of 0-36 for a total possible score of 0 to 99 with higher scores representing greater disability. A negative change from Baseline indicates improvement. Change from Baseline in mFARS-neuro was analyzed using MMRM ANCOVA with Baseline mFARS-neuro as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline mFARS-neuro-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Modified Friedreich Ataxia Rating Scale Neurological Examination (mFARS-neuro) Total Score Change from Baseline at Week 2	-3.36 score on a scale Standard Error 0.650	-0.70 score on a scale Standard Error 0.919	-0.58 score on a scale Standard Error 0.647
Change From Baseline in the Modified Friedreich Ataxia Rating Scale Neurological Examination (mFARS-neuro) Total Score Change from Baseline at Week 7	-2.41 score on a scale Standard Error 0.799	-2.01 score on a scale Standard Error 1.114	-1.35 score on a scale Standard Error 0.828
Change From Baseline in the Modified Friedreich Ataxia Rating Scale Neurological Examination (mFARS-neuro) Total Score Change from Baseline at Week 12	-3.30 score on a scale Standard Error 0.762	-1.28 score on a scale Standard Error 1.057	-1.19 score on a scale Standard Error 0.752

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

The mFARS-neuro neurological examination is a clinician-rated measure based on neural substrates affected in Friedreich ataxia including: bulbar on a scale of 0-11, upper limb coordination on a scale of 0-36, lower limb coordination on a scale of 0-16, and upright stability/gait functions on a scale of 0-36, with the higher scores representing greater disability. A negative change from Baseline indicates improvement. Change from Baseline in mFARS-neuro was analyzed using MMRM ANCOVA with Baseline mFARS-neuro as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline mFARS-neuro-by visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 7, Upright Stability	-0.2 unit on a scale Standard Error 0.27	-0.8 unit on a scale Standard Error 0.38	0.4 unit on a scale Standard Error 0.28
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 2, Bulbar	0.08 unit on a scale Standard Error 0.080	0.15 unit on a scale Standard Error 0.112	0.14 unit on a scale Standard Error 0.082
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 7, Bulbar	0.01 unit on a scale Standard Error 0.074	-0.08 unit on a scale Standard Error 0.102	0.17 unit on a scale Standard Error 0.079
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 12, Bulbar	0.01 unit on a scale Standard Error 0.085	0.06 unit on a scale Standard Error 0.118	0.21 unit on a scale Standard Error 0.087
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 2, Upper Limb Coordination	-1.55 unit on a scale Standard Error 0.425	0.44 unit on a scale Standard Error 0.601	-0.53 unit on a scale Standard Error 0.419
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 7, Upper Limb Coordination	-0.90 unit on a scale Standard Error 0.533	0.17 unit on a scale Standard Error 0.741	-0.72 unit on a scale Standard Error 0.547
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 12, Upper Limb Coordination	-1.19 unit on a scale Standard Error 0.608	0.02 unit on a scale Standard Error 0.848	-0.65 unit on a scale Standard Error 0.602
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 2, Lower Limb Coordination	-0.92 unit on a scale Standard Error 0.292	-0.52 unit on a scale Standard Error 0.415	-0.14 unit on a scale Standard Error 0.289
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 7, Lower Limb Coordination	-0.84 unit on a scale Standard Error 0.494	-0.88 unit on a scale Standard Error 0.691	-0.67 unit on a scale Standard Error 0.516
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 12, Lower Limb Coordination	-1.62 unit on a scale Standard Error 0.449	-0.63 unit on a scale Standard Error 0.625	-0.67 unit on a scale Standard Error 0.445
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 2, Upright Stability	-0.5 unit on a scale Standard Error 0.37	-0.3 unit on a scale Standard Error 0.53	0.5 unit on a scale Standard Error 0.38
Change From Baseline in the mFARS-neuro Subscales Scores Change at Week 12, Upright Stability	-0.1 unit on a scale Standard Error 0.35	-0.3 unit on a scale Standard Error 0.48	0.4 unit on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

mFARS-neuro examination is a clinician-rated measure based on neural substrates affected in Friedreich ataxia individual items:Cough,Speech,Right(R)Finger to Finger Test,Left(L)Finger to Finger Test,R-Nose to Finger Test,L-Nose to Finger Test,R-Dysmetria Test,L-Dysmetria Test,Rapid Alternating Movement(RAM)of R-Hands,RAM of L-Hands,R-Finger Taps(FT),L-FT,R-Heel Along Shin Slide,L-Heel Along Shin Slide,R-Heel Along Shin Tap,L-Heel Along Shin Tap,Siting Posture,Stance Feet Apart(SFA)-3 Trial Average(TTA),SFA(Eyes Closed)-TTA,Stance Feet Together(SFT)-TTA,SFT(Eyes Closed)-TTA,Tandem Stance-TTA,Stance on Dominant Foot-TTA,Tandem Walk and Gait.Items were scored on scale of 0 to 2,3,4 or 5,with higher scores indicating greater disability.Negative change from Baseline(BL)indicates improvement.Change from BL in mFARS-neuro was analyzed using MMRM ANCOVA with BL as covariate;pooled site,visit,treatment,ambulation status as fixed factors;treatment-by-visit,BL mFARS-neuro-by visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Tandem Walk (0-3)	0.0 score on a scale Standard Error 0.05	-0.1 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.05
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Cough (0-2)	0.06 score on a scale Standard Error 0.051	0.07 score on a scale Standard Error 0.072	0.06 score on a scale Standard Error 0.051
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Cough (0-2)	0.01 score on a scale Standard Error 0.063	-0.05 score on a scale Standard Error 0.087	0.11 score on a scale Standard Error 0.065
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Cough (0-2)	0.01 score on a scale Standard Error 0.063	0.08 score on a scale Standard Error 0.088	0.13 score on a scale Standard Error 0.063
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Speech (0-3)	0.00 score on a scale Standard Error 0.058	0.08 score on a scale Standard Error 0.083	0.10 score on a scale Standard Error 0.060
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Speech (0-3)	0.00 score on a scale Standard Error 0.043	-0.04 score on a scale Standard Error 0.060	0.07 score on a scale Standard Error 0.045
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Speech (0-3)	0.00 score on a scale Standard Error 0.056	0.00 score on a scale Standard Error 0.079	0.09 score on a scale Standard Error 0.057
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2,Right Finger to Finger Test(0-3)	0.10 score on a scale Standard Error 0.079	0.17 score on a scale Standard Error 0.109	0.06 score on a scale Standard Error 0.078
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7,Right Finger to Finger Test(0-3)	0.04 score on a scale Standard Error 0.075	0.12 score on a scale Standard Error 0.102	-0.02 score on a scale Standard Error 0.075
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12,Right Finger to Finger Test(0-3)	0.21 score on a scale Standard Error 0.077	0.12 score on a scale Standard Error 0.105	0.06 score on a scale Standard Error 0.074
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Finger Taps (0-4)	-0.22 score on a scale Standard Error 0.132	0.28 score on a scale Standard Error 0.189	-0.17 score on a scale Standard Error 0.132
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Finger Taps (0-4)	-0.37 score on a scale Standard Error 0.131	0.22 score on a scale Standard Error 0.182	-0.21 score on a scale Standard Error 0.136
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Left Finger Taps (0-4)	-0.50 score on a scale Standard Error 0.161	0.07 score on a scale Standard Error 0.225	-0.17 score on a scale Standard Error 0.160
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2,Right Heel Along Shin Slide(0-4)	-0.24 score on a scale Standard Error 0.118	-0.04 score on a scale Standard Error 0.166	-0.24 score on a scale Standard Error 0.117
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Finger to Finger Test (0-3)	0.04 score on a scale Standard Error 0.085	0.13 score on a scale Standard Error 0.120	0.07 score on a scale Standard Error 0.084
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Finger to Finger Test (0-3)	0.05 score on a scale Standard Error 0.075	0.07 score on a scale Standard Error 0.104	0.07 score on a scale Standard Error 0.077
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7,Right Heel Along Shin Slide(0-4)	-0.18 score on a scale Standard Error 0.152	-0.32 score on a scale Standard Error 0.209	-0.35 score on a scale Standard Error 0.155
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12,Right Heel Along Shin Slide(0-4)	-0.43 score on a scale Standard Error 0.164	-0.09 score on a scale Standard Error 0.223	-0.30 score on a scale Standard Error 0.160
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Heel Along Shin Slide (0-4)	0.01 score on a scale Standard Error 0.121	-0.15 score on a scale Standard Error 0.174	0.05 score on a scale Standard Error 0.121
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Tandem Walk (0-3)	0.0 score on a scale Standard Error 0.06	-0.1 score on a scale Standard Error 0.08	0.0 score on a scale Standard Error 0.06
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Heel Along Shin Slide (0-4)	0.08 score on a scale Standard Error 0.133	-0.23 score on a scale Standard Error 0.187	-0.09 score on a scale Standard Error 0.138
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12,Left Heel Along Shin Slide(0-4)	-0.16 score on a scale Standard Error 0.151	-0.18 score on a scale Standard Error 0.210	-0.15 score on a scale Standard Error 0.149
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Right Heel Along Shin Tap (0-4)	-0.39 score on a scale Standard Error 0.114	-0.17 score on a scale Standard Error 0.159	0.04 score on a scale Standard Error 0.113
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12,Left Finger to Finger Test(0-3)	0.13 score on a scale Standard Error 0.095	0.22 score on a scale Standard Error 0.132	0.04 score on a scale Standard Error 0.093
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Right Heel Along Shin Tap (0-4)	-0.14 score on a scale Standard Error 0.163	-0.41 score on a scale Standard Error 0.224	-0.14 score on a scale Standard Error 0.168
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Right Heel Along Shin Tap (0-4)	-0.32 score on a scale Standard Error 0.137	-0.18 score on a scale Standard Error 0.184	0.01 score on a scale Standard Error 0.131
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Heel Along Shin Tap (0-4)	-0.38 score on a scale Standard Error 0.121	-0.22 score on a scale Standard Error 0.171	-0.05 score on a scale Standard Error 0.120
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Heel Along Shin Tap (0-4)	-0.36 score on a scale Standard Error 0.165	0.01 score on a scale Standard Error 0.230	-0.15 score on a scale Standard Error 0.171
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Left Heel Along Shin Tap (0-4)	-0.52 score on a scale Standard Error 0.180	-0.21 score on a scale Standard Error 0.251	-0.27 score on a scale Standard Error 0.178
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Siting Posture (0-4)	-0.3 score on a scale Standard Error 0.11	-0.1 score on a scale Standard Error 0.15	-0.1 score on a scale Standard Error 0.11
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Siting Posture (0-4)	-0.4 score on a scale Standard Error 0.11	-0.5 score on a scale Standard Error 0.15	-0.2 score on a scale Standard Error 0.11
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Siting Posture (0-4)	-0.1 score on a scale Standard Error 0.12	-0.3 score on a scale Standard Error 0.16	-0.1 score on a scale Standard Error 0.11
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, SFA -TTA (0-4)	-0.1 score on a scale Standard Error 0.15	0.0 score on a scale Standard Error 0.21	-0.1 score on a scale Standard Error 0.15
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, SFA - TTA (0-4)	0.1 score on a scale Standard Error 0.12	0.0 score on a scale Standard Error 0.17	-0.1 score on a scale Standard Error 0.12
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, SFA - TTA (0-4)	-0.1 score on a scale Standard Error 0.13	0.0 score on a scale Standard Error 0.19	0.0 score on a scale Standard Error 0.13
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, SFA (Eyes Closed) - TTA (0-4)	0.0 score on a scale Standard Error 0.07	0.1 score on a scale Standard Error 0.10	-0.1 score on a scale Standard Error 0.07
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, SFA (Eyes Closed) - TTA (0-4)	0.2 score on a scale Standard Error 0.11	0.1 score on a scale Standard Error 0.16	0.0 score on a scale Standard Error 0.12
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, SFA (Eyes Closed) - TTA (0-4)	0.2 score on a scale Standard Error 0.14	0.2 score on a scale Standard Error 0.19	0.0 score on a scale Standard Error 0.14
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, SFT - TTA (0-4)	0.0 score on a scale Standard Error 0.18	-0.3 score on a scale Standard Error 0.26	0.4 score on a scale Standard Error 0.19
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, SFT - TTA (0-4)	-0.1 score on a scale Standard Error 0.11	-0.1 score on a scale Standard Error 0.15	0.3 score on a scale Standard Error 0.11
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, SFT - TTA (0-4)	0.0 score on a scale Standard Error 0.14	-0.2 score on a scale Standard Error 0.19	0.3 score on a scale Standard Error 0.14
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, SFT (Eyes Closed) - TTA (0-4)	0.1 score on a scale Standard Error 0.06	0.1 score on a scale Standard Error 0.09	0.0 score on a scale Standard Error 0.06
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, SFT (Eyes Closed) - TTA (0-4)	0.1 score on a scale Standard Error 0.06	0.1 score on a scale Standard Error 0.09	0.1 score on a scale Standard Error 0.07
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, SFT (Eyes Closed) - TTA (0-4)	0.0 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.09	-0.1 score on a scale Standard Error 0.06
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Tandem Stance - TTA (0-4)	0.0 score on a scale Standard Error 0.05	0.0 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.05
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Tandem Stance - TTA (0-4)	0.0 score on a scale Standard Error 0.05	-0.1 score on a scale Standard Error 0.07	0.1 score on a scale Standard Error 0.05
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Tandem Stance - TTA (0-4)	0.1 score on a scale Standard Error 0.05	0.0 score on a scale Standard Error 0.07	0.1 score on a scale Standard Error 0.05
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2,Stance on Dominant Foot-TTA(0-4)	NA score on a scale Standard Error NA The least squares (LS) mean and standard error (SE) was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7,Stance on Dominant Foot-TTA(0-4)	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12,Stance on Dominant Foot-TTA(0-4)	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.	NA score on a scale Standard Error NA The LS mean and SE was not estimable as there was no change from baseline in subscale score at this time point.
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Tandem Walk (0-3)	0.0 score on a scale Standard Error 0.05	0.0 score on a scale Standard Error 0.07	0.0 score on a scale Standard Error 0.05
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Gait (0-5)	-0.3 score on a scale Standard Error 0.12	-0.2 score on a scale Standard Error 0.17	0.2 score on a scale Standard Error 0.12
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Right Nose to Finger Test (0-4)	-0.08 score on a scale Standard Error 0.085	0.21 score on a scale Standard Error 0.126	0.06 score on a scale Standard Error 0.085
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Gait (0-5)	-0.1 score on a scale Standard Error 0.11	-0.3 score on a scale Standard Error 0.15	0.2 score on a scale Standard Error 0.11
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Gait (0-5)	-0.1 score on a scale Standard Error 0.11	-0.2 score on a scale Standard Error 0.15	0.1 score on a scale Standard Error 0.10
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Right Nose to Finger Test (0-4)	0.01 score on a scale Standard Error 0.103	0.09 score on a scale Standard Error 0.147	-0.07 score on a scale Standard Error 0.107
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Right Nose to Finger Test (0-4)	0.00 score on a scale Standard Error 0.098	-0.15 score on a scale Standard Error 0.140	0.00 score on a scale Standard Error 0.097
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Nose to Finger Test (0-4)	-0.05 score on a scale Standard Error 0.096	0.08 score on a scale Standard Error 0.137	0.05 score on a scale Standard Error 0.095
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Nose to Finger Test (0-4)	0.15 score on a scale Standard Error 0.095	0.32 score on a scale Standard Error 0.133	0.01 score on a scale Standard Error 0.098
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Left Nose to Finger Test (0-4)	0.11 score on a scale Standard Error 0.103	0.10 score on a scale Standard Error 0.141	0.14 score on a scale Standard Error 0.099
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Right Dysmetria Test (0-4)	-0.11 score on a scale Standard Error 0.106	-0.15 score on a scale Standard Error 0.151	0.01 score on a scale Standard Error 0.105
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Right Dysmetria Test (0-4)	-0.23 score on a scale Standard Error 0.129	-0.11 score on a scale Standard Error 0.181	-0.06 score on a scale Standard Error 0.134
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Right Dysmetria Test (0-4)	-0.11 score on a scale Standard Error 0.132	0.01 score on a scale Standard Error 0.185	-0.16 score on a scale Standard Error 0.130
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Left Dysmetria Test (0-4)	-0.27 score on a scale Standard Error 0.111	0.02 score on a scale Standard Error 0.160	-0.12 score on a scale Standard Error 0.110
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Left Dysmetria Test (0-4)	-0.02 score on a scale Standard Error 0.136	-0.26 score on a scale Standard Error 0.191	-0.16 score on a scale Standard Error 0.141
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Left Dysmetria Test (0-4)	-0.17 score on a scale Standard Error 0.151	-0.11 score on a scale Standard Error 0.211	0.06 score on a scale Standard Error 0.149
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, RAM of Right Hands (0-3)	-0.18 score on a scale Standard Error 0.103	0.05 score on a scale Standard Error 0.145	-0.06 score on a scale Standard Error 0.102
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, RAM of Right Hands (0-3)	0.03 score on a scale Standard Error 0.122	-0.03 score on a scale Standard Error 0.170	0.03 score on a scale Standard Error 0.126
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, RAM of Right Hands (0-3)	-0.07 score on a scale Standard Error 0.113	0.12 score on a scale Standard Error 0.156	-0.12 score on a scale Standard Error 0.112
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, RAM of Left Hands (0-3)	-0.11 score on a scale Standard Error 0.085	-0.03 score on a scale Standard Error 0.120	-0.03 score on a scale Standard Error 0.085
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, RAM of Left Hands (0-3)	-0.08 score on a scale Standard Error 0.123	0.01 score on a scale Standard Error 0.173	0.05 score on a scale Standard Error 0.129
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, RAM of Left Hands (0-3)	-0.20 score on a scale Standard Error 0.096	0.11 score on a scale Standard Error 0.133	0.02 score on a scale Standard Error 0.095
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 2, Right Finger Taps (0-4)	-0.39 score on a scale Standard Error 0.121	0.05 score on a scale Standard Error 0.172	-0.23 score on a scale Standard Error 0.124
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 7, Right Finger Taps (0-4)	-0.18 score on a scale Standard Error 0.136	0.04 score on a scale Standard Error 0.190	-0.19 score on a scale Standard Error 0.143
Change From Baseline in the mFARS-neuro Individual Item Scores Change at Week 12, Right Finger Taps (0-4)	-0.31 score on a scale Standard Error 0.140	-0.13 score on a scale Standard Error 0.195	-0.37 score on a scale Standard Error 0.140

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7 and 12

The participant was instructed to walk 25 feet as quickly as possible, but safely. The time was calculated from the initiation of the instruction to start and ends when the participant has reached the 25-foot mark. The task was immediately administered again by having the participant walk back the same distance. The two trials were averaged. A negative change from Baseline indicates improvement. Change from Baseline in T25FW was analyzed using MMRM ANCOVA with Baseline T25FW as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline T25FW-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the Timed 25-Foot Walk (T25FW) Change from Baseline at Week 2	0.61 seconds Standard Error 0.901	0.84 seconds Standard Error 1.124	1.95 seconds Standard Error 0.990
Change From Baseline in the Timed 25-Foot Walk (T25FW) Change from Baseline at Week 7	1.67 seconds Standard Error 0.948	1.77 seconds Standard Error 1.255	1.37 seconds Standard Error 1.080
Change From Baseline in the Timed 25-Foot Walk (T25FW) Change from Baseline at Week 12	0.52 seconds Standard Error 0.903	2.70 seconds Standard Error 1.226	1.30 seconds Standard Error 1.057

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

9-HPT and T25FW were evaluated together as a performance-based composite measure. The inverse transform of each score was computed. The inverse scores from each test were tabulated and converted to test-specific Z scores by subtracting the cohort mean from the raw score, and then dividing by the cohort standard deviation (SD) to create a Z score for the test. The composite Z scores were created by subtracting Z-score for T25FW from the Z-score for 9-HPT-1. A larger Z-score represents a better outcome. A positive change from Baseline indicates improvement. Change from Baseline in composite score was analyzed using MMRM ANCOVA with Baseline composite score as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline composite score-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the 9-HPT and T25FW Composite Score Change from Baseline at Week 2	0.1369 z-score Standard Error 0.21905	0.1819 z-score Standard Error 0.28555	-0.1911 z-score Standard Error 0.24051
Change From Baseline in the 9-HPT and T25FW Composite Score Change from Baseline at Week 7	-0.1112 z-score Standard Error 0.24167	0.0336 z-score Standard Error 0.32731	-0.0998 z-score Standard Error 0.26792
Change From Baseline in the 9-HPT and T25FW Composite Score Change from Baseline at Week 12	0.0060 z-score Standard Error 0.22484	-0.2007 z-score Standard Error 0.31057	0.1233 z-score Standard Error 0.25501

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and, 12

The LCLA test assessed visual function in both eyes using the Low-Contrast Sloan Letter Charts at different contrast levels. The score ranged from 0 to 70, where 0=worst visual functioning and 70=best visual functioning. A positive change from Baseline indicates improvement. The change from Baseline in LCLA was analyzed using MMRM ANCOVA with Baseline LCLA as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline LCLA-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in Low-Contrast Letter Acuity (LCLA) Test Score Change from Baseline at Week 2	1.8 score on a scale Standard Error 2.56	-0.9 score on a scale Standard Error 3.61	5.1 score on a scale Standard Error 2.53
Change From Baseline in Low-Contrast Letter Acuity (LCLA) Test Score Change from Baseline at Week 7	4.6 score on a scale Standard Error 2.20	-2.3 score on a scale Standard Error 3.06	6.0 score on a scale Standard Error 2.17
Change From Baseline in Low-Contrast Letter Acuity (LCLA) Test Score Change from Baseline at Week 12	0.0 score on a scale Standard Error 2.61	-5.7 score on a scale Standard Error 3.65	3.1 score on a scale Standard Error 2.56

SECONDARY outcome

Timeframe: Weeks 2, 7, and 12

The clinician used the CGI-I scale to assess the participant's improvement (or worsening) overall relative to Baseline on a 7-point scale where: 1=Much improved, 2=Moderately improved, 3=A little improved, 4=No change, 5=A little worse, 6=Moderately worse and 7=Much worse. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 7, No Change	11 Participants	8 Participants	11 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 7, A little Worse	1 Participants	1 Participants	1 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 12, Moderately Improved	1 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 12, A Little Improved	9 Participants	3 Participants	7 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 12, No Change	12 Participants	7 Participants	16 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 12, A little Worse	2 Participants	1 Participants	1 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 2, Moderately Improved	1 Participants	0 Participants	2 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 2, A Little Improved	14 Participants	3 Participants	6 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 2, No Change	11 Participants	10 Participants	17 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 2, A little Worse	1 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 7, Moderately Improved	1 Participants	0 Participants	1 Participants
Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories Week 7, A Little Improved	13 Participants	4 Participants	8 Participants

SECONDARY outcome

Timeframe: Weeks 2, 7 and 12

The participant used the PGI-I scale to assess their improvement (or worsening) overall relative to Baseline on a 7-point scale where: 1=Much improved, 2=Moderately improved, 3=A little improved, 4=No change, 5=A little worse, 6=Moderately worse and 7=Much worse. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, Moderately Improved	5 Participants	1 Participants	1 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, A Little Improved	8 Participants	4 Participants	3 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 2, Moderately Improved	2 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 2, A Little Improved	6 Participants	3 Participants	8 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 2, No Change	19 Participants	10 Participants	16 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 2, A little Worse	0 Participants	0 Participants	2 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 7, Moderately Improved	3 Participants	0 Participants	3 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 7, A Little Improved	10 Participants	4 Participants	5 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 7, No Change	11 Participants	8 Participants	14 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 7, A little Worse	2 Participants	1 Participants	2 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, Much Improved	1 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, No Change	7 Participants	7 Participants	15 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, A little Worse	3 Participants	0 Participants	4 Participants
Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories Week 12, Moderately Worse	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Weeks 2, 7, and 12

The clinician used the CGI-I scale to assess the participant's improvement (or worsening) in upper extremity function relative to Baseline on a 7-point scale where: 1=Much improved, 2=Moderately improved, 3=A little improved, 4=No change, 5=A little worse, 6=Moderately worse and 7=Much worse. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 2, Moderately Improved	1 Participants	0 Participants	2 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 2, A Little Improved	13 Participants	2 Participants	7 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 2, No Change	12 Participants	11 Participants	16 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 2, A little Worse	1 Participants	0 Participants	0 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 7, Moderately Improved	1 Participants	1 Participants	0 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 7, A Little Improved	10 Participants	5 Participants	11 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 7, No Change	14 Participants	6 Participants	7 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 7, A little Worse	1 Participants	1 Participants	3 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 12, Moderately Improved	2 Participants	2 Participants	0 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 12, A Little Improved	11 Participants	2 Participants	9 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 12, No Change	9 Participants	7 Participants	15 Participants
Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories Week 12, A little Worse	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 2, 7, and 12

The participant used the PGI-I scale to assess their improvement (or worsening) in upper extremity function relative to Baseline on a 7-point scale where: 1=Much improved, 2=Moderately improved, 3=A little improved, 4=No change, 5=A little worse, 6=Moderately worse and 7=Much worse. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 2, Moderately Improved	5 Participants	0 Participants	0 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 2, A Little Improved	6 Participants	3 Participants	7 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 2, No Change	16 Participants	10 Participants	18 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 2, A little Worse	0 Participants	0 Participants	1 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 7, Much Improved	0 Participants	0 Participants	1 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 7, Moderately Improved	3 Participants	0 Participants	2 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 7, A Little Improved	10 Participants	4 Participants	4 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 7, No Change	11 Participants	7 Participants	15 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 7, A little Worse	2 Participants	2 Participants	2 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 12, Much Improved	2 Participants	0 Participants	0 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 12, Moderately Improved	6 Participants	1 Participants	1 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 12, A Little Improved	6 Participants	4 Participants	6 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 12, No Change	9 Participants	7 Participants	15 Participants
Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories Week 12, A little Worse	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

The clinician used the CGI-S scale to assess the severity of the participant's disease overall on a 5-point scale where: 0=No symptoms, 1=Mild, 2=Moderate, 3=Severe and 4=Very severe. The number of participants by CGI-S score category is reported relative to their CGI-S score at Baseline. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=4 (Very Severe)	1 Participants	1 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=1 (Mild)	2 Participants	2 Participants	1 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=2 (Moderate)	4 Participants	2 Participants	2 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=1 (Mild)	1 Participants	0 Participants	2 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=2 (Moderate)	14 Participants	6 Participants	10 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=3 (Severe)	2 Participants	0 Participants	1 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	1 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=3 (Severe)	3 Participants	2 Participants	8 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=1 (Mild)	2 Participants	1 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=2 (Moderate)	3 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=1 (Mild)	1 Participants	1 Participants	3 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=2 (Moderate)	14 Participants	8 Participants	11 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=3 (Severe)	3 Participants	1 Participants	2 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=3 (Severe)	2 Participants	1 Participants	7 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=4 (Very Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=4 (Very Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=4 (Very Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=4 (Very Severe) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=4 (Very Severe) · Score at Baseline=4 (Very Severe)	1 Participants	1 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=1 (Mild)	2 Participants	1 Participants	2 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=2 (Moderate)	4 Participants	0 Participants	1 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=1 (Mild)	1 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=2 (Moderate)	13 Participants	8 Participants	11 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=3 (Severe)	2 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	1 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=3 (Severe)	1 Participants	1 Participants	9 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=4 (Very Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=4 (Very Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=4 (Very Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=4 (Very Severe) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	—
Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=4 (Very Severe) · Score at Baseline=4 (Very Severe)	1 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

The participant assessed the severity of their disease overall using the PGI-S 5-point scale where: 0=No symptoms, 1=Mild, 2=Moderate, 3=Severe and 4=Very severe. The number of participants by PGI-S score category is reported relative to their PGI-S score at Baseline. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=1 (Mild)	5 Participants	1 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=1 (Mild)	2 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=2 (Moderate)	2 Participants	3 Participants	3 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=1 (Mild)	2 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=2 (Moderate)	11 Participants	5 Participants	16 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=3 (Severe)	3 Participants	3 Participants	1 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=3 (Severe)	3 Participants	1 Participants	4 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	—	—
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=1 (Mild)	0 Participants	—	—
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=2 (Moderate)	0 Participants	—	—
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=3 (Severe)	1 Participants	—	—
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 2=4 (Very Severe) · Score at Baseline=4 (Very Severe)	0 Participants	—	—
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=1 (Mild)	4 Participants	1 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=2 (Moderate)	1 Participants	2 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=2 (Moderate)	12 Participants	4 Participants	14 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=3 (Severe)	4 Participants	3 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	2 Participants	1 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=3 (Severe)	3 Participants	1 Participants	3 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 7=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=1 (Mild)	4 Participants	1 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=2 (Moderate)	2 Participants	2 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=3 (Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mild) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=1 (Mild)	2 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=2 (Moderate)	10 Participants	4 Participants	15 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=3 (Severe)	4 Participants	3 Participants	3 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderate) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=0 (No Symptoms)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=1 (Mild)	0 Participants	0 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=2 (Moderate)	0 Participants	1 Participants	0 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=3 (Severe)	2 Participants	1 Participants	2 Participants
Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline Score at Week 12=3 (Severe) · Score at Baseline=4 (Very Severe)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 2, 7, and 12

The clinician used the CGI-S scale to assess the severity of the participant's upper extremity function on a 5-point scale where: 0=Not impaired, 1=Mildly impaired, 2=Moderately impaired, 3=Severely impaired and 4=Very severely impaired. The number of participants by CGI-S score category is reported relative to their CGI-S score at Baseline. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	13 Participants	3 Participants	11 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	2 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	2 Participants	2 Participants	2 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	11 Participants	5 Participants	8 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	1 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 2=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	10 Participants	4 Participants	9 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	2 Participants	3 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	4 Participants	1 Participants	3 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	9 Participants	5 Participants	8 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	1 Participants	0 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 7=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	10 Participants	3 Participants	9 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	2 Participants	2 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	4 Participants	1 Participants	4 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	7 Participants	5 Participants	8 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	1 Participants	0 Participants	0 Participants
Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline Score at Week 12=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7, and 12

The participant assessed the severity of their upper extremity function using the PGI-S 5-point scale where: 0=Not impaired, 1=Mildly impaired, 2=Moderately impaired, 3=Severely impaired and 4=Very severely impaired. The number of participants by PGI-S score category is reported relative to their PGI-S score at Baseline. Only those score categories reported for at least one participant at the given time-point are presented.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=3 (Severely Impaired) · Score at Baseline=1 (Mildly Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=3 (Severely Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	1 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=3 (Severely Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=3 (Severely Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=0 (Not Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=0 (Not Impaired) · Score at Baseline=1 (Mildly Impaired)	1 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=0 (Not Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=0 (Not Impaired) · Score at Baseline=1 (Mildly Impaired)	0 Participants	1 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=0 (Not Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=0 (Not Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=0 (Not Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	1 Participants	1 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	11 Participants	2 Participants	9 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	2 Participants	1 Participants	2 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	3 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=0 (Not Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	1 Participants	1 Participants	5 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	11 Participants	5 Participants	6 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=3 (Severely Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=3 (Severely Impaired) · Score at Baseline=1 (Mildly Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=3 (Severely Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	1 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=3 (Severely Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 2=3 (Severely Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=0 (Not Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=0 (Not Impaired) · Score at Baseline=1 (Mildly Impaired)	1 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=0 (Not Impaired) · Score at Baseline=2 (Moderately Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=0 (Not Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	1 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=0 (Not Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	1 Participants	1 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	8 Participants	1 Participants	9 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	2 Participants	3 Participants	5 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	2 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	3 Participants	3 Participants	4 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	11 Participants	4 Participants	3 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 7=3 (Severely Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=0 (Not Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=0 (Not Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=1 (Mildly Impaired) · Score at Baseline=0 (Not Impaired)	1 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=1 (Mildly Impaired) · Score at Baseline=1 (Mildly Impaired)	9 Participants	2 Participants	11 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=1 (Mildly Impaired) · Score at Baseline=2 (Moderately Impaired)	3 Participants	1 Participants	2 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=1 (Mildly Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	3 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=1 (Mildly Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=2 (Moderately Impaired) · Score at Baseline=0 (Not Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=2 (Moderately Impaired) · Score at Baseline=1 (Mildly Impaired)	2 Participants	2 Participants	2 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=2 (Moderately Impaired) · Score at Baseline=2 (Moderately Impaired)	8 Participants	7 Participants	6 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=2 (Moderately Impaired) · Score at Baseline=3 (Severely Impaired)	0 Participants	0 Participants	0 Participants
Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories Score at Week 12=2 (Moderately Impaired) · Score at Baseline=4 (Very Severely Impaired)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 7 and 12

The ADL component of the FARS includes 9 subscales: speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function. Items 3 to 5 are directly related to upper limb function. Each of these subscales is rated on a 5-point scale where 0=normal to 4=severe disability/inability to carry out activity independently for a total possible score of 0 to 12, with higher scores representing greater disability/dependency. A negative change from Baseline indicates improvement. Change from Baseline in Friedreich ataxia rating scale activities of daily living (FARS ADL) upper limb function items was analyzed using MMRM ANCOVA with Baseline FARS ADL as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline FARS ADL-by-visit interactions.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Change From Baseline in the ADL Component Score for Upper Limb Function Items of the FARS Change from Baseline at Week 2	-0.21 score on a scale Standard Error 0.213	-0.40 score on a scale Standard Error 0.308	0.34 score on a scale Standard Error 0.212
Change From Baseline in the ADL Component Score for Upper Limb Function Items of the FARS Change from Baseline at Week 7	-0.17 score on a scale Standard Error 0.202	-0.14 score on a scale Standard Error 0.289	0.16 score on a scale Standard Error 0.203
Change From Baseline in the ADL Component Score for Upper Limb Function Items of the FARS Change from Baseline at Week 12	-0.15 score on a scale Standard Error 0.240	-0.05 score on a scale Standard Error 0.345	0.19 score on a scale Standard Error 0.240

SECONDARY outcome

Timeframe: Baseline up to Week 12

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.	TAK-831 75 mg n=14 Participants TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.	TAK-831 300 mg n=26 Participants TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
Number of Participants With at Least a 15 Percent (%) or at Least a 20% Reduction in 9-HPT Completion Time From Baseline At Least 15% Reduction from Baseline	3 Participants	0 Participants	0 Participants
Number of Participants With at Least a 15 Percent (%) or at Least a 20% Reduction in 9-HPT Completion Time From Baseline At Least 20% Reduction from Baseline	2 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

TAK-831 75 mg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

TAK-831 300 mg

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Neurocrine Medical Information

Neurocrine Biosciences

Phone: 877-641-3461

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Generally, the PI may publish results of the study following the publication of results by the Sponsor.
Publication restrictions are in place

Restriction type: OTHER